The DOI matches its Crossref record; 35 of the 36 references it cites were found in a registry or an index; 22 of the 35 sources its claims cite were checked for support.
Unmodified mRNA in LNPs constitutes a competitive technology for prophylactic vaccines
Open accessAbstract
mRNA represents a promising new vaccine technology platform with high flexibility in regard to development and production. Here, we demonstrate that vaccines based on sequence optimized, chemically unmodified mRNA formulated in optimized lipid nanoparticles (LNPs) are highly immunogenic and well tolerated in non-human primates (NHPs). Single intramuscular vaccination of NHPs with LNP-formulated mRNAs encoding rabies or influenza antigens induced protective antibody titers, which could be boosted and remained stable during an observation period of up to 1 year. First mechanistic insights into the mode of action of the LNP-formulated mRNA vaccines demonstrated a strong activation of the innate immune response at the injection site and in the draining lymph nodes (dLNs). Activation of the innate immune system was reflected by a transient induction of pro-inflammatory cytokines and chemokines and activation of the majority of immune cells in the dLNs. Notably, our data demonstrate that mRNA vaccines can compete with licensed vaccines based on inactivated virus or are even superior in respect of functional antibody and T cell responses. Importantly, we show that the developed LNP-formulated mRNA vaccines can be used as a vaccination platform allowing multiple, sequential vaccinations against different pathogens. These results provide strong evidence that the mRNA technology is a valid approach for the development of effective prophylactic vaccines to prevent infectious diseases.
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
Sequence-optimized, chemically unmodified mRNA formulated in lipid nanoparticles (LNPs) induced protective antibody titers and durable immune responses in non-human primates after intramuscular vaccination. The platform was well tolerated, boostable, usable for sequential vaccination against different pathogens, and competitive with or superior to licensed inactivated-virus vaccines in humoral and T cell responses.
Key findings
- A single intramuscular dose of LNP-formulated RABV-G mRNA induced rabies virus neutralization titers at or above the WHO protective threshold of 0.5 IU/ml in all non-human primates at day 28; a 10-fold higher mRNA dose yielded 10-fold higher titers. A single 10 µg dose of H1N1-HA mRNA/LNP induced H1N1 hemagglutination inhibition titers at or above the protective 1:40 threshold.
- Boosting increased rabies VNTs 20-fold; titers stabilized at about 40 IU/ml for the 10 µg dose and about 4 IU/ml for the 1 µg dose. Recall vaccination 5 months later produced a rapid 10-fold VNT increase. H1N1-HI titers stabilized at about 640 and remained above the protective limit for 5 months, with stable titers until the end of a 1-year observation period.
- Compared with licensed vaccines, RABV-G mRNA/LNP after one shot gave median VNTs of 4.9 IU/ml (10 µg) and 71.2 IU/ml (100 µg) versus 1.8 IU/ml for Rabipur®; after boost, 100 µg mRNA reached median 842 IU/ml versus 31.3 IU/ml for Rabipur®. H3N2-HA mRNA/LNP was comparable to or higher than Fluad®, and mRNA/LNP induced antigen-specific CD4+ and CD8+ T cell responses that were absent in Rabipur®- or Fluad®-vaccinated animals.
- LNP-formulated mRNA induced transient local pro-inflammatory cytokines and chemokines, with TNF and IL-6 peaking at 14 h; more than 90% of T and B cells in draining lymph nodes expressed CD69 at 24 h, and CD11b+ Gr1+ cells increased 10-fold within 4 h. Injection-site reactions were limited to slight erythema and/or edema resolving in 1–6 days, with no pain on palpation.
Methods
- Mice (BALB/c, 7–9 weeks) were vaccinated intramuscularly into the tibialis anterior with 25 µl at days 0 and 21; cynomolgus monkeys were vaccinated intramuscularly into the biceps femoris with 500 µl at days 0 and 28, with NHP groups of n = 2 male and 2 female per group.
- Vaccines used sequence-optimized, chemically unmodified mRNA in LNPs composed of an ionizable amino lipid, phospholipid, cholesterol, and PEGylated lipid, encoding RABV-G, H1N1-HA, H3N2-HA, luciferase, or non-translatable fluorescent mRNA; licensed comparators were Rabipur® and Fluad®.
- Analyses included in vivo luciferase imaging, cytokine/chemokine measurement by cytometric bead array or Luminex, flow cytometry of draining lymph nodes, rabies VNT by FAVN, influenza HI assays, intracellular cytokine staining, safety observations, and Mann–Whitney statistical tests.
Limitations
- The paper states that further investigations are required to determine whether monocytes and granulocytes contribute to antigen transport to draining lymph nodes. It also notes that the vaccinated non-human primates were naïve to the influenza strains used, unlike most adult humans who have prior exposure or vaccination, so human responses may differ.
- Evident from the text: NHP immunogenicity groups were small (n = 2 male, 2 female per group), and protection in NHPs was inferred from antibody correlates rather than live-virus challenge. The paper also states that the technology warrants clinical testing, so no human efficacy data are reported.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Figures
Verification
Claims the paper makes
60 Own result · 22 Own interpretation · 7 Partly supported · 7 No full text of the sources · 4 Supported · 2 Supported so far · 1 No basis given · accuracy not yet measured
Every source the paper cites for this claim was checked and supports it.
In the paper
“Importantly, protective efficacy against Zika virus challenge infections was also demonstrated in non-human primates (NHPs) after i.d. vaccination.14”
§ Unmodified mRNA in LNPs constitutes a competitive technology for prophylactic vaccines > Introduction
What the sources say
- Supportedcites [14] Pardi, N. et al. Zika virus protection by a single low-dose nucleoside-modified mRNA vaccination. Nature https://doi.org/10.1038/nature21428 (2017). source
The paper reports that rhesus macaques were immunized intradermally and then challenged with Zika virus at week 5. In the passage labeled Abstract, four of five vaccinated macaques had no detectable viremia, while all six controls became infected; the fifth vaccinated animal had only a low, transient viral signal. (LLM, conf=0.94)
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“In recent publications chemically modified nucleosides were used to reach sufficient antigen expression,12–15 which is in contrast to our proprietary mRNA technology, which employs sequence optimization and selected untranslated regions (UTRs) to achieve high antigen expression.16”
§ Unmodified mRNA in LNPs constitutes a competitive technology for prophylactic vaccines > Introduction
What the sources say
- Supportedcites [12] Richner, J. M. et al. Modified mRNA vaccines protect against zika virus infection. Cell. https://doi.org/10.1016/j.cell.2017.02.017 (2017). source
The Introduction says the vaccine uses a nucleoside modification to limit innate immune activation, which can otherwise inhibit translation and reduce antigen expression. The Results (‘An mRNA vaccine platform for ZIKV’) also describe modified mRNA designed to induce high protein expression in vivo. (LLM, conf=0.92)
- Partly supportedcites [13] Richner, J. M. et al. Vaccine mediated protection against zika virus-induced congenital disease. Cell 170, 273–283.e12 (2017). sourceExperimental — accuracy not yet measured
The Method Details section (page unavailable) confirms that the vaccine mRNA used a chemically modified nucleoside, substituting 1-methylpseudoUTP for UTP. It attributes increased translation efficiency to the cap structure, while the Discussion (page unavailable) says modified nucleosides were used to minimize innate immune activation; the paper does not establish that the nucleoside modification was used to reach sufficient antigen expression. (LLM, conf=0.85)
- Supportedcites [14] Pardi, N. et al. Zika virus protection by a single low-dose nucleoside-modified mRNA vaccination. Nature https://doi.org/10.1038/nature21428 (2017). source
The Abstract states that the vaccine mRNA contains 1-methylpseudouridine, a modified nucleoside that increases mRNA translation in vivo. It also reports production of the encoded ZIKV E antigen in transfected cells, supporting the claim that modified nucleosides were used to achieve antigen expression. (LLM, conf=0.91)
- Supportedcites [15] Bahl, K. et al. Preclinical and clinical demonstration of immunogenicity by mRNA vaccines against H10N8 and H7N9 Influenza Viruses. Mol. Ther. J. Am. Soc. Gene Ther. 25, 1316–1327 (2017). source
The Introduction says that replacing uridine with modified nucleosides can overcome immune activation that inhibits mRNA translation and reduces antigen expression. The Discussion says the paper’s modified-mRNA vaccine technology balances immune stimulation with antigen expression and produces high transient protein levels. (LLM, conf=0.91)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“In these studies, mice were vaccinated i.m. with LNP-formulated mRNA vaccines inducing protection against Zika virus challenge infections,12 and protection against placental damage and fetal demise in challenged pregnant mice.13”
§ Unmodified mRNA in LNPs constitutes a competitive technology for prophylactic vaccines > Introduction
What the sources say
- Supportedcites [13] Richner, J. M. et al. Vaccine mediated protection against zika virus-induced congenital disease. Cell 170, 273–283.e12 (2017). source
The Results section, “Activity of a prM-E mRNA LNP vaccine in pregnancy,” describes intramuscular vaccination before mating and Zika virus challenge during pregnancy. The Results section, “Vaccine protection against placental and fetal injury,” reports less placental damage and survival of all fetuses from prM-E-vaccinated dams, compared with fetal demise in placebo-vaccinated dams. Page numbers are not provided in our copy. (LLM, conf=0.94)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“The study by Pardi et al. demonstrates that non-replicating mRNA is able to induce antibody titers in NHPs.”
§ Unmodified mRNA in LNPs constitutes a competitive technology for prophylactic vaccines > Introduction
What the sources say
- Supportedcites [14] Pardi, N. et al. Zika virus protection by a single low-dose nucleoside-modified mRNA vaccination. Nature https://doi.org/10.1038/nature21428 (2017). source
The mRNA production section describes a vaccine encoding ZIKV prM-E glycoproteins, consistent with non-replicating mRNA. The macaque findings (section labeled Abstract; page unavailable) report that vaccination induced E-specific IgG and neutralizing antibody titers in rhesus macaques, a non-human primate species. (LLM, conf=0.91)
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“In recent publications chemically modified nucleosides were used to reach sufficient antigen expression,12–15 which is in contrast to our proprietary mRNA technology, which employs sequence optimization and selected untranslated regions (UTRs) to achieve high antigen expression.16”
§ Unmodified mRNA in LNPs constitutes a competitive technology for prophylactic vaccines > Introduction
What the sources say
- Partly supportedcites [16] Thess, A. et al. Sequence-engineered mRNA without chemical nucleoside modifications enables an effective protein therapy in large animals. Mol. Ther. J. Am. Soc. Gene Ther. 23, 1456–1464 (2015). sourceExperimental — accuracy not yet measured
The Materials and Methods describe codon optimization and selection of 5′ and 3′ UTRs, and the Results report high expression from sequence-engineered mRNA. However, the expression experiments described in the Results use luciferase and erythropoietin, not an antigen; the source does not establish high antigen expression specifically. Page numbers were not provided in our copy. (LLM, conf=0.85)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“In these studies, mice were vaccinated i.m. with LNP-formulated mRNA vaccines inducing protection against Zika virus challenge infections,12 and protection against placental damage and fetal demise in challenged pregnant mice.13”
§ Unmodified mRNA in LNPs constitutes a competitive technology for prophylactic vaccines > Introduction
What the sources say
- Supportedcites [12] Richner, J. M. et al. Modified mRNA vaccines protect against zika virus infection. Cell. https://doi.org/10.1016/j.cell.2017.02.017 (2017). source
The Results section (“Vaccine efficacy in C57BL/6 mice”) reports intramuscular vaccination with an mRNA LNP vaccine and protection against lethal ZIKV challenge. The separate claim about pregnant mice is attached to another citation and is not part of this verdict. (LLM, conf=0.94)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Activation of the innate immune system was reflected by a transient induction of pro-inflammatory cytokines and chemokines and activation of the majority of immune cells in the dLNs.”
§ Unmodified mRNA in LNPs constitutes a competitive technology for prophylactic vaccines > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Single intramuscular vaccination of NHPs with LNP-formulated mRNAs encoding rabies or influenza antigens induced protective antibody titers, which could be boosted and remained stable during an observation period of up to 1 year.”
§ Unmodified mRNA in LNPs constitutes a competitive technology for prophylactic vaccines > Abstract
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Here, we demonstrate that vaccines based on sequence optimized, chemically unmodified mRNA formulated in optimized lipid nanoparticles (LNPs) are highly immunogenic and well tolerated in non-human primates (NHPs).”
§ Unmodified mRNA in LNPs constitutes a competitive technology for prophylactic vaccines > Abstract
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Single intramuscular vaccination of NHPs with LNP-formulated mRNAs encoding rabies or influenza antigens induced protective antibody titers, which could be boosted and remained stable during an observation period of up to 1 year.”
§ Unmodified mRNA in LNPs constitutes a competitive technology for prophylactic vaccines > Abstract
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- It may state two separate claims as one. 32
- Probably not a substantial claim. 1
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Vaccines based on mRNA could meet these requirements because they offer multifaceted advantages including flexible antigen design, a cost-effective manufacturing process allowing for parallel production of multiple mRNA vaccines1–5 and rapid manufacturing, which could be of crucial importance during pandemics.6”
§ Unmodified mRNA in LNPs constitutes a competitive technology for prophylactic vaccines > Introduction
What the sources say
- Not checked — no full text of the sourcecites [1] Hoerr, I., Obst, R., Rammensee, H. G. & Jung, G. In vivo application of RNA leads to induction of specific cytotoxic T lymphocytes and antibodies. Eur. J. Immunol. 30, 1–7 (2000). source
- Partly supportedcites [2] Kallen, K.-J. et al. A novel, disruptive vaccination technology: self-adjuvanted RNActive(®) vaccines. Hum. Vaccines Immunother. 9, 2263–2276 (2013). sourceExperimental — accuracy not yet measured
The Introduction describes nucleotide-based vaccines as a simple, inexpensive platform compatible with protein engineering, and the Conclusion describes RNA production as flexible and scalable with modest investment (page numbers unavailable). The paper does not establish parallel production of multiple mRNA vaccines. Rapid manufacturing is attached to a separate citation in the citing sentence, not specifically to this source. (LLM, conf=0.84)
- Partly supportedcites [3] Sullenger, B. A. & Nair, S. From the RNA world to the clinic. Science 352, 1417–1420 (2016). sourceExperimental — accuracy not yet measured
The “Therapeutic coding RNAs: mRNA-based immunotherapy” section describes mRNA vaccines encoding different tumor or viral antigens and says direct-injection approaches could replace more complicated and costly cell-based therapies. It does not establish a cost-effective manufacturing process or parallel production of multiple vaccines. Rapid manufacturing is attached to a separate citation in the citing sentence. (LLM, conf=0.83)
- Not checked — no full text of the sourcecites [4] Ulmer, J. B. & Geall, A. J. Recent innovations in mRNA vaccines. Curr. Opin. Immunol. 41, 18–22 (2016). source
- Could not verifycites [5] Nabel, G. J. Designing tomorrow’s vaccines. N. Engl. J. Med 368, 551–560 (2013). sourceExperimental — accuracy not yet measured
The opening section says older vaccine technologies were ill-suited to a rapid response to the 2009 H1N1 pandemic, but it does not say mRNA vaccines can be manufactured rapidly. The passages on manufacturing and gene-based delivery likewise do not address mRNA vaccine production, its cost, or parallel production (searched: mRNA vaccines, messenger RNA, rapid manufacturing). (LLM, conf=0.76)
- Could not verifycites [6] Koff, W. C. et al. Accelerating next-generation vaccine development for global disease prevention. Science 340, 1232910 (2013). sourceExperimental — accuracy not yet measured
The Introduction and Antigen Discovery Technologies sections discuss advances in vaccine design generally, but do not address the claimed advantages of mRNA vaccines. Searches for mRNA, manufacturing, and parallel production found no passage in our copy that substantiates those advantages; the citing sentence assigns rapid manufacturing to a separate citation. (LLM, conf=0.75)
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“This approach was specifically optimized for i.d. administration and showed lower efficacy when given by the intramuscular route (i.m.) as preferred route for prophylactic vaccination, highlighting the important role of formulation in vaccine design.”
§ Unmodified mRNA in LNPs constitutes a competitive technology for prophylactic vaccines > Introduction
What the sources say
- Partly supportedcites [7] Schnee, M. et al. An mRNA vaccine encoding rabies virus glycoprotein induces protection against lethal infection in mice and correlates of protection in adult and newborn pigs. PLoS Negl. Trop. Dis. 10, e0004746 (2016). sourceExperimental — accuracy not yet measured
Materials and Methods (mRNA- and protein-based vaccines; page unavailable) says the vaccine contained no chemically modified nucleotides. The Immunizations procedure (page unavailable) says the mRNA vaccine was given intradermally, but describes no intramuscular mRNA group. The copy describes optimization of the mRNA and its formulation, not optimization specifically for intradermal delivery, and does not establish lower efficacy by the intramuscular route. (LLM, conf=0.84)
- Not checked — no full text of the sourcecites [8] Petsch, B. et al. Protective efficacy of in vitro synthesized, specific mRNA vaccines against influenza A virus infection. Nat. Biotechnol. 30, 1210–1216 (2012). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Meanwhile, induction of protective immune responses against two different influenza strains could be demonstrated also after i.m. administration in NHPs and humans, again using LNP-formulated mRNA vaccines based on chemically modified nucleosides.15”
§ Unmodified mRNA in LNPs constitutes a competitive technology for prophylactic vaccines > Introduction
What the sources say
- Partly supportedcites [15] Bahl, K. et al. Preclinical and clinical demonstration of immunogenicity by mRNA vaccines against H10N8 and H7N9 Influenza Viruses. Mol. Ther. J. Am. Soc. Gene Ther. 25, 1316–1327 (2017). sourceExperimental — accuracy not yet measured
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Partly supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Studies with self-amplifying mRNA vaccines investigated the effect of different formulations such as lipid-nanoparticles (LNP)10 or cationic nanoemulsion (CNE)11 on the immunogenicity of mRNA vaccines. Self-amplifying vaccines benefited from formulation with LNP or CNE and were able to induce protective antibody titers.”
§ Unmodified mRNA in LNPs constitutes a competitive technology for prophylactic vaccines > Introduction
What the sources say
- Supportedcites [10] Geall, A. J. et al. Nonviral delivery of self-amplifying RNA vaccines. Proc. Natl. Acad. Sci. USA 109, 14604–14609 (2012). source
The paper is cited for the LNP formulation; the citing sentence assigns CNE to a separate citation. In “Protection from Virus Challenge” (page unavailable), LNP-formulated self-amplifying RNA raised RSV-neutralizing antibody titers tenfold over naked RNA, above the threshold correlated with protection in cotton rats. (LLM, conf=0.94)
- Not checked — no full text of the sourcecites [11] Brito, L. A. et al. A cationic nanoemulsion for the delivery of next-generation RNA vaccines. Mol. Ther. J. Am. Soc. Gene Ther. 22, 2118–2129 (2014). source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Using exclusively unmodified nucleosides, we have demonstrated that non-replicating mRNA vaccines are immunogenic and capable of inducing protection against lethal rabies and influenza virus infections after intradermal vaccination (i.d.) in mice, rats, ferrets, and pigs.7,8”
§ Unmodified mRNA in LNPs constitutes a competitive technology for prophylactic vaccines > Introduction
What the sources say
- Partly supportedcites [7] Schnee, M. et al. An mRNA vaccine encoding rabies virus glycoprotein induces protection against lethal infection in mice and correlates of protection in adult and newborn pigs. PLoS Negl. Trop. Dis. 10, e0004746 (2016). sourceExperimental — accuracy not yet measured
Materials and Methods states that the rabies mRNA contained no chemically modified nucleotides and that mice and pigs received intradermal injections. The Abstract reports protection against lethal rabies challenge in mice, while the Results report protective-correlate antibody titers—not challenge-proven protection—in pigs. This paper does not establish the sentence’s influenza or rat and ferret claims. (LLM, conf=0.90)
- Not checked — no full text of the sourcecites [8] Petsch, B. et al. Protective efficacy of in vitro synthesized, specific mRNA vaccines against influenza A virus infection. Nat. Biotechnol. 30, 1210–1216 (2012). source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Recent studies using chemically modified mRNA revealed protective efficacy of LNP-formulated mRNA vaccines for Zika virus after i.m. administration in mice or i.d. administration in NHPs, as well as immunogenicity for influenza HA of the strains H10N8 and H7N9 after i.m. administration in NHPs and humans.12–15”
§ Unmodified mRNA in LNPs constitutes a competitive technology for prophylactic vaccines > Discussion
What the sources say
- Partly supportedcites [12] Richner, J. M. et al. Modified mRNA vaccines protect against zika virus infection. Cell. https://doi.org/10.1016/j.cell.2017.02.017 (2017). sourceExperimental — accuracy not yet measured
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
- Partly supportedcites [13] Richner, J. M. et al. Vaccine mediated protection against zika virus-induced congenital disease. Cell 170, 273–283.e12 (2017). sourceExperimental — accuracy not yet measured
Split into 2 atoms — 1 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 1 unverifiable. Expand the claim to see per-atom verdicts.
- Partly supportedcites [14] Pardi, N. et al. Zika virus protection by a single low-dose nucleoside-modified mRNA vaccination. Nature https://doi.org/10.1038/nature21428 (2017). sourceExperimental — accuracy not yet measured
Split into 2 atoms — 1 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 1 unverifiable. Expand the claim to see per-atom verdicts.
- Partly supportedcites [15] Bahl, K. et al. Preclinical and clinical demonstration of immunogenicity by mRNA vaccines against H10N8 and H7N9 Influenza Viruses. Mol. Ther. J. Am. Soc. Gene Ther. 25, 1316–1327 (2017). sourceExperimental — accuracy not yet measured
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“We have previously demonstrated that i.d. administration of protamine-formulated prophylactic mRNA vaccines based on unmodified nucleosides can protect mice against influenza or rabies challenge infections and induces also in ferrets and pigs strong humoral responses.7,8”
§ Unmodified mRNA in LNPs constitutes a competitive technology for prophylactic vaccines > Discussion
What the sources say
- Supportedcites [7] Schnee, M. et al. An mRNA vaccine encoding rabies virus glycoprotein induces protection against lethal infection in mice and correlates of protection in adult and newborn pigs. PLoS Negl. Trop. Dis. 10, e0004746 (2016). source
The Methods describe intradermal administration of protamine-complexed mRNA without chemically modified nucleotides. The Introduction reports protection against rabies challenge in mice and virus-neutralizing antibody responses in adult and newborn pigs. This rabies paper supports those portions of the sentence; the sentence also cites another source for the influenza and ferret portions. (LLM, conf=0.91)
- Not checked — no full text of the sourcecites [8] Petsch, B. et al. Protective efficacy of in vitro synthesized, specific mRNA vaccines against influenza A virus infection. Nat. Biotechnol. 30, 1210–1216 (2012). source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The strongest elevation in cell numbers was observed 24 h after injection, except for NK cells which increased over time.”
§ Unmodified mRNA in LNPs constitutes a competitive technology for prophylactic vaccines > Results > Unmodified mRNA in LNPs supports high antigen expression in muscle cells and induces a pro-inflammatory environment
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The increase in cellularity in dLNs was accompanied by a strong activation of both adaptive and innate immune cells, which peaked at 24 h after injection, when more than 90% of the T and B cells expressed the activation marker CD69 (Fig. 2h).”
§ Unmodified mRNA in LNPs constitutes a competitive technology for prophylactic vaccines > Results > Unmodified mRNA in LNPs supports high antigen expression in muscle cells and induces a pro-inflammatory environment
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The IL-6 concentrations remained 10-fold lower in the serum compared to the injection site and returned to baseline at 96 h after injection (Fig. 2c).”
§ Unmodified mRNA in LNPs constitutes a competitive technology for prophylactic vaccines > Results > Unmodified mRNA in LNPs supports high antigen expression in muscle cells and induces a pro-inflammatory environment
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Importantly, the increase in cytokine concentrations was predominantly local with systemic TNF concentrations below detection limit and only a transient increase in IL-6 concentrations.”
§ Unmodified mRNA in LNPs constitutes a competitive technology for prophylactic vaccines > Results > Unmodified mRNA in LNPs supports high antigen expression in muscle cells and induces a pro-inflammatory environment
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The immune responses could be boosted and stayed stable during an observation period of up to 1 year.”
§ Unmodified mRNA in LNPs constitutes a competitive technology for prophylactic vaccines > Introduction
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In contrast to the LNP formulation, the non-LNP formulation did not induce antigen-specific humoral responses and no H3N2-HI titers could be detected after prime or boost vaccination (Supplementary Fig. 1).”
§ Unmodified mRNA in LNPs constitutes a competitive technology for prophylactic vaccines > Results > Intramuscular vaccination with LNP-formulated mRNA leads to long-lived humoral responses in NHPs
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Antibody titers of all groups benefited from a second vaccination given at day 28, and VNTs (measured on day 49) induced by 100 µg of mRNA vaccine reached a median of 842 IU/ml, outperforming Rabipur® more than 20-fold (median 31.3 IU/ml).”
§ Unmodified mRNA in LNPs constitutes a competitive technology for prophylactic vaccines > Results > LNP-formulated mRNA vaccines are capable of competing with licensed vaccines in NHPs
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“A second dose of both vaccines further increased the titers, to yet higher titers for the mRNA/LNP vaccine.”
§ Unmodified mRNA in LNPs constitutes a competitive technology for prophylactic vaccines > Results > LNP-formulated mRNA vaccines are capable of competing with licensed vaccines in NHPs
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The RABV-G mRNA/LNP vaccine induced after a single vaccination neutralizing antibody titers above 0.5 IU/ml, which were comparable (for the 10 µg mRNA dose) or higher (for the 100 µg mRNA dose) than the VNTs induced by a full human dose of Rabipur® (Fig. 5a).”
§ Unmodified mRNA in LNPs constitutes a competitive technology for prophylactic vaccines > Results > LNP-formulated mRNA vaccines are capable of competing with licensed vaccines in NHPs
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We observed that i.m. application of unmodified mRNA in optimized LNPs led to high expression of the encoded protein in mice, which translated into strong humoral and cellular immune responses.”
§ Unmodified mRNA in LNPs constitutes a competitive technology for prophylactic vaccines > Discussion
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Importantly, all vaccinated animals maintained H1N1-HI titers clearly above the protective limit for 5 months starting after prime vaccination pointing to longevity of the mRNA-mediated humoral response.”
§ Unmodified mRNA in LNPs constitutes a competitive technology for prophylactic vaccines > Results > Intramuscular vaccination with LNP-formulated mRNA leads to long-lived humoral responses in NHPs
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Systemic cytokine concentrations after vaccination stayed for most animals and time points below the detection limit (IL-1β, IL-4, IL-5, IFN-γ and TNF) or did not increase significantly above pre-dose concentrations (IL-2, IL-8 and G-CSF)”
§ Unmodified mRNA in LNPs constitutes a competitive technology for prophylactic vaccines > Results > mRNA vaccines exhibit a favorable safety profile
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Monitoring the antibody titers for 6 months we could demonstrate that after an initial decline neutralizing titers stabilized at a level of about 40 IU/ml for the 10 µg mRNA dose and about 4 IU/ml for the 1 µg mRNA dose (Fig. 4b).”
§ Unmodified mRNA in LNPs constitutes a competitive technology for prophylactic vaccines > Results > Intramuscular vaccination with LNP-formulated mRNA leads to long-lived humoral responses in NHPs
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“A single dose of the H3N2-HA mRNA/LNP vaccine was sufficient to induce H3N2-HI titers, which were above the titer of 1:40 and comparable to titers induced by a full human dose of Fluad®.”
§ Unmodified mRNA in LNPs constitutes a competitive technology for prophylactic vaccines > Results > LNP-formulated mRNA vaccines are capable of competing with licensed vaccines in NHPs
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“A second dose of the H1N1-HA mRNA/LNP vaccine strongly increased the H1N1-HI titers, which again after an initial decline stabilized at a titer of about 640 (Fig. 4e).”
§ Unmodified mRNA in LNPs constitutes a competitive technology for prophylactic vaccines > Results > Intramuscular vaccination with LNP-formulated mRNA leads to long-lived humoral responses in NHPs
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We observed only limited reactogenicity at the injection site and minor changes in systemic cytokine and chemokine concentrations.”
§ Unmodified mRNA in LNPs constitutes a competitive technology for prophylactic vaccines > Discussion
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The mRNA/LNP vaccines induced even CD4+ and CD8+ T cell responses against RABV-G and CD4+ T cell responses against H3N2-HA, which were absent in NHPs that had received the licensed vaccines Rabipur® or Fluad®”
§ Unmodified mRNA in LNPs constitutes a competitive technology for prophylactic vaccines > Discussion
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Notably, our data demonstrate that mRNA vaccines can compete with licensed vaccines based on inactivated virus or are even superior in respect of functional antibody and T cell responses.”
§ Unmodified mRNA in LNPs constitutes a competitive technology for prophylactic vaccines > Abstract
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Taken together, these results suggest that i.m. injection of LNP-formulated mRNA vaccines induces a broad but transient local immunostimulatory milieu, which is relevant for the induction of strong adaptive immune responses.”
§ Unmodified mRNA in LNPs constitutes a competitive technology for prophylactic vaccines > Results > Unmodified mRNA in LNPs supports high antigen expression in muscle cells and induces a pro-inflammatory environment
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“the Zika studies used mRNA harboring 1-methylpseudouridine (m1Ψ) which has been demonstrated to reduce immunostimulation and increase protein expression.26”
§ Unmodified mRNA in LNPs constitutes a competitive technology for prophylactic vaccines > Discussion
What the sources say
- Not checked — no full text of the sourcecites [26] Andries, O. et al. N(1)-methylpseudouridine-incorporated mRNA outperforms pseudouridine-incorporated mRNA by providing enhanced protein expression and reduced immunogenicity in mammalian cell lines and mice. J. Control. Release 217, 337–344 (2015). source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The specific approach we describe here yields strong immunogenicity in NHPs, which is even superior to licensed vaccines based on inactivated virus.”
§ Unmodified mRNA in LNPs constitutes a competitive technology for prophylactic vaccines > Discussion
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“An important finding of our study is that LNP-formulated mRNA can be used as a platform technology, which does not induce anti-vector immunity that can be observed with viral vectors such as adenoviruses.29”
§ Unmodified mRNA in LNPs constitutes a competitive technology for prophylactic vaccines > Discussion
What the sources say
- Not checked — no full text of the sourcecites [29] Lopez-Gordo, E., Podgorski, I. I., Downes, N. & Alemany, R. Circumventing antivector immunity: potential use of nonhuman adenoviral vectors. Hum. Gene Ther. 25, 285–300 (2014). source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In summary, we demonstrated that intramuscular application of LNP-formulated prophylactic mRNA vaccines based on sequence-optimized, unmodified nucleosides leads to a strong induction of local innate immune responses and systemic adaptive immune responses.”
§ Unmodified mRNA in LNPs constitutes a competitive technology for prophylactic vaccines > Discussion
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Here, we demonstrate that mRNA vaccines can compete with or even outperform licensed vaccines.”
§ Unmodified mRNA in LNPs constitutes a competitive technology for prophylactic vaccines > Discussion
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Notably, the humoral and cellular immune responses in NHP induced by mRNA/LNP vaccines against rabies and influenza H3N2 were superior to the licensed vaccines Rabipur® and Fluad®, respectively.”
§ Unmodified mRNA in LNPs constitutes a competitive technology for prophylactic vaccines > Discussion
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The maintenance of the H1N1-HI titers during the RABV-G mRNA vaccinations and the induction of high titers of rabies neutralizing antibodies in H1N1-HA-vaccinated animals using the same vaccine format suggest that LNP-formulated mRNA enables multiple prophylactic vaccinations.”
§ Unmodified mRNA in LNPs constitutes a competitive technology for prophylactic vaccines > Discussion
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper relies on this without support.
Muscle tissue has low infiltration by immune cells and lacks costimulatory molecules and optimal antigen presentation on muscle cells.
“The induction of strong immune responses after intramuscular injection of mRNA represents a very high hurdle due to a low infiltration of muscle tissue by immune cells and the lack of costimulatory molecules and optimal antigen presentation on muscle cells.”
The paper relies on this without support.
Potent intramuscular mRNA vaccines must allow high antigen expression and presentation and induce strong immunostimulatory signals to improve immune cell infiltration.
“Thus, potent intramuscular mRNA vaccines must allow high antigen expression and presentation and induce strong immunostimulatory signals to improve immune cell infiltration.”
The paper relies on this without support.
Immunogenicity and protection data in non-human primates predict efficacy of prophylactic vaccines in humans.
“In the present study, we compare mRNA vaccines to licensed vaccines based on inactivated virus and demonstrate that unmodified mRNA, formulated in optimized LNPs, fulfills all the key requirements to be a viable vaccine platform for human prophylaxis.”
The paper relies on this without support.
Fluad® contains the surface antigens HA and neuraminidase of the influenza strains H1N1, H3N2 and B/Brisbane, as well as the adjuvant MF59C.1.
“Fluad® contains the surface antigens HA and neuraminidase of the influenza strains H1N1, H3N2 and B/Brisbane, as well as the adjuvant MF59C.1.”
The paper relies on this without support.
Nonhuman primates mimic the human situation most closely.
“we tested whether this also translates to NHPs, which mimic the human situation most closely.”
The paper relies on this without support.
The antibody titers measured serve as correlates of protection for rabies and influenza.
“were maintained during this period well above the titers that serve as correlate of protection.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Due to their intrinsic immunostimulatory capacities, LNP-formulated mRNAs with unmodified nucleotides are a potent modality to deliver antigens for presentation on HLA class I and II molecules.”
From Preclinical development of an mRNA-based multiepitope immunotherapeutic for glioblastoma (2025) · cites this paper as [22]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“They primarily induce CD8+ T-cell responses [22], which can exceed those induced by LNP-formulated mRNAs with modified nucleotides [34, 35], as well as CD4+ T-cell responses.”
From Preclinical development of an mRNA-based multiepitope immunotherapeutic for glioblastoma (2025) · cites this paper as [22]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Both CVnCoV and CV2CoV are based on RNActive technology4–7 and consist of non-chemically modified sequence-engineered mRNA without pseudouridine6–12.”
From Optimization of non-coding regions for a non-modified mRNA COVID-19 vaccine (2022) · cites this paper as [8]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“preclinical studies showed that protecting the mRNA by lipid encapsulation significantly enhanced the response to the CV7201 [9], [24].”
From Proof-of-concept of a low-dose unmodified mRNA-based rabies vaccine formulated with lipid nanoparticles in human volunteers: A phase 1 trial (2021) · cites this paper as [9]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Further preclinical research in animal models has found that formulation of the mRNA in lipid nanoparticles (LNP) protects the mRNA and enhances the immune response [9].”
From Proof-of-concept of a low-dose unmodified mRNA-based rabies vaccine formulated with lipid nanoparticles in human volunteers: A phase 1 trial (2021) · cites this paper as [9]
The cited source says what the claim attributes to it.
In the citing paper
“Intracellular delivery of oligonucleotides can be improved by encapsulating them in lipid nanoparticles (LNP) [9], [23]”
From Proof-of-concept of a low-dose unmodified mRNA-based rabies vaccine formulated with lipid nanoparticles in human volunteers: A phase 1 trial (2021) · cites this paper as [9]
In the citing paper
“In non-human primates, two 100 µg doses spaced 28 days apart were well tolerated and provoked 20-fold higher antibody titres than a commercially licensed rabies vaccine189.”
From mRNA vaccines for infectious diseases: principles, delivery and clinical translation (2021) · cites this paper as [189]
In the citing paper
“in phase I trials of CV7202, a 5 μg dose had unacceptable reactogenicity, and 1 μg was the highest dose that was well tolerated.”
From mRNA vaccines for infectious diseases: principles, delivery and clinical translation (2021) · cites this paper as [189]
In the citing paper
“in phase I trials of CV7202, a 5 μg dose had unacceptable reactogenicity, and 1 μg was the highest dose that was well tolerated.”
From mRNA vaccines for infectious diseases: principles, delivery and clinical translation (2021) · cites this paper as [189]
In the citing paper
“prompting CureVac to adopt LNPs as their preferred delivery platform for their subsequent rabies candidate CV7202 (ref.189).”
From mRNA vaccines for infectious diseases: principles, delivery and clinical translation (2021) · cites this paper as [189]
In the citing paper
“In their final COVID-19 vaccines, both BioNTech and Moderna have made use of a highly-purified and N1-methyl-pseudouridine (1mΨ) modified mRNA. In contrast, CureVac has applied its “unmodified” mRNA vaccine technology”
From The dawn of mRNA vaccines: the COVID-19 case (2021) · cites this paper as [11]
In the citing paper
“the CVnCoV vaccine candidate contains an “unmodified” mRNA, which employs sequence engineering (e.g., reduction in uridine content), selected UTRs, and a stringent purification protocol to remove dsRNA fragments [11]”
From The dawn of mRNA vaccines: the COVID-19 case (2021) · cites this paper as [11]
In the citing paper
“Several preclinical studies have indicated that an unmodified mRNA platform induces a more pronounced type-I IFN-polarized innate immune response [11,62]”
From The dawn of mRNA vaccines: the COVID-19 case (2021) · cites this paper as [11]
In the citing paper
“Similar to the more classical vaccine approaches, the COVID-19 mRNA vaccines are injected in the muscle, where they trigger localized and transient inflammation that recruits different immune cells to the injection site (Fig. 3 ) [11,41]”
From The dawn of mRNA vaccines: the COVID-19 case (2021) · cites this paper as [11]
In the citing paper
“owing to their relatively small size (~100 nm), neutral surface charge and diffusible PEG lipid coating, mRNA LNPs might also enter the lymphatics to directly target LN-resident APCs and B cells [11,58]”
From The dawn of mRNA vaccines: the COVID-19 case (2021) · cites this paper as [11]
Citations
Cites
Karikó, K., Buckstein, M., Ni, H., & Weissman, D. (2005) · Immunity · doi:10.1016/j.immuni.2005.06.008 · Cited by 2,728
T-cell quality in memory and protection: implications for vaccine design
Seder, R. A., Darrah, P. A., & Roederer, M. (2008) · Nature reviews. Immunology · doi:10.1038/nri2274 · Cited by 1,565
Maximizing the potency of siRNA lipid nanoparticles for hepatic gene silencing in vivo
Jayaraman, M., Ansell, S. M., Mui, B. L., Tam, Y. K., Chen, J., Du, X., Butler, D., Eltepu, L., Matsuda, S., Narayanannair, J. K., et al. (2012) · Angewandte Chemie International Edition · doi:10.1002/anie.201203263 · Cited by 1,267 · cited 2×
“Several mechanisms have been described how LNPs containing ionizable amino lipids could enhance cellular delivery of nucleic acids.(27) Firstly, they self-assemble with the polyanionic mRNA to form particles, which provide protection of the mRNA from RNases and improve uptake of the mRNA by endocytosis.”
BackgroundMethodSelf-citationPardi, N., Tuyishime, S., Muramatsu, H., Kariko, K., Mui, B. L., Tam, Y. K., Madden, T. D., Hope, M. J., & Weissman, D. (2015) · Journal of Controlled Release · doi:10.1016/j.jconrel.2015.08.007 · Cited by 1,014
Self-citationCXCR3 ligands: redundant, collaborative and antagonistic functions
Groom, J. R., & Luster, A. D. (2011) · Immunology and Cell Biology · doi:10.1038/icb.2010.158 · Cited by 1,006
Safety and efficacy of RNAi therapy for transthyretin amyloidosis
Coelho, T., Adams, D., Silva, A., Lozeron, P., Hawkins, P. N., Mant, T., Perez, J., Chiesa, J., Warrington, S., Tranter, E., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1208760 · Cited by 971
Modified mRNA vaccines protect against zika virus infection
Richner, J. M., Himansu, S., Dowd, K. A., Butler, S. L., Salazar, V., Fox, J. M., Julander, J. G., Tang, W. W., Shresta, S., Pierson, T. C., et al. (2017) · Cell · doi:10.1016/j.cell.2017.02.017 · Cited by 909
Zika virus protection by a single low-dose nucleoside-modified mRNA vaccination
Pardi, N., Hogan, M. J., Pelc, R. S., Muramatsu, H., Andersen, H., DeMaso, C. R., Dowd, K. A., Sutherland, L. L., Scearce, R. M., Parks, R., et al. (2017) · Nature · doi:10.1038/nature21428 · Cited by 884 · cited 1×
“vaccination.(14) Immunogenicity data in NHPs are absolutely desirable taking into account the experiences with early DNA vaccines, for which efficacy could not be translated from mice to NHPs.”
BackgroundSelf-citationVaccines: Correlates of Vaccine‐Induced Immunity
Plotkin, S. A. (2008) · Clinical Infectious Diseases · doi:10.1086/589862 · Cited by 829
The who's who of T ‐cell differentiation: Human memory T ‐cell subsets
Mahnke, Y. D., Brodie, T. M., Sallusto, F., Roederer, M., & Lugli, E. (2013) · European Journal of Immunology · doi:10.1002/eji.201343751 · Cited by 817
Cited by
Sorted by citations
Items 101–200 of 257
Engineered mRNA Delivery Systems for Biomedical Applications
Wang, J., Zhu, H., Gan, J., Liang, G., Li, L., & Zhao, Y. (2023) · Advanced Materials · doi:10.1002/adma.202308029 · Cited by 46
Huang, L., Rong, Y., Pan, Q., Yi, K., Tang, X., Zhang, Q., Wang, W., Wu, J., & Wang, X. (2020) · Asian Journal of Pharmaceutical Sciences · doi:10.1016/j.ajps.2020.08.001 · Cited by 40
“[61] Lutz J , Lazzaro S , Habbeddine M , Schmidt KE , Baumhof P , Mui BL , et al.”
Chan, L., Alizadeh, K., Alizadeh, K., Fazel, F., Kakish, J. E., Karimi, N., Knapp, J. P., Mehrani, Y., Minott, J. A., Morovati, S., et al. (2021) · Vaccines · doi:10.3390/vaccines9090979 · Cited by 40
Tetrahydropyrimidine Ionizable Lipids for Efficient mRNA Delivery
Isaac, I., Shaikh, A., Bhatia, M., Liu, Q., Park, S., & Bhattacharya, C. (2024) · ACS Nano · doi:10.1021/acsnano.4c10154 · Cited by 39
Korzun, T., Moses, A. S., Diba, P., Sattler, A. L., Taratula, O. R., Sahay, G., Taratula, O., & Marks, D. L. (2023) · Pharmaceuticals · doi:10.3390/ph16081088 · Cited by 40
Demystifying mRNA vaccines: an emerging platform at the forefront of cryptic diseases
Rouf, N. Z., Biswas, S., Tarannum, N., Oishee, L. M., & Muna, M. M. (2022) · RNA Biology · doi:10.1080/15476286.2022.2055923 · Cited by 39
Influenza Viruses: Innate Immunity and mRNA Vaccines
Lee, S., & Ryu, J. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.710647 · Cited by 36
mRNA vaccine platforms: linking infectious disease prevention and cancer immunotherapy
Haghmorad, D., Eslami, M., Orooji, N., Halabitska, I., Kamyshna, I. I., Kamyshnyi, O., & Oksenych, V. (2025) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2025.1547025 · Cited by 42
Sohi, A. N., Kiani, J., Arefian, E., Khosrojerdi, A., Fekrirad, Z., Ghaemi, S., Zim, M. K., Jalili, A., Bostanshirin, N., & Soleimani, M. (2021) · Vaccines · doi:10.3390/vaccines9091007 · Cited by 32
Current state of, prospects for, and obstacles to mRNA vaccine development
Aljabali, A. A. A., Bashatwah, R. M., Obeid, M. A., Mishra, V., Mishra, Y., Serrano‐Aroca, Á., Lundstrom, K. H., & Tambuwala, M. M. (2022) · Drug Discovery Today · doi:10.1016/j.drudis.2022.103458 · Cited by 35
mRNA-based VP8* nanoparticle vaccines against rotavirus are highly immunogenic in rodents
Roier, S., Prasad, V. M., McNeal, M., Lee, K. K., Petsch, B., & Rauch, S. (2023) · npj Vaccines · doi:10.1038/s41541-023-00790-z · Cited by 33
Scaria, P. V., Roth, N., Schwendt, K., Muratova, O. V., Alani, N., Lambert, L., Barnafo, E. K., Rowe, C. G., Zaidi, I., Rausch, K. M., et al. (2024) · npj Vaccines · doi:10.1038/s41541-023-00783-y · Cited by 36
Lipid-Based Delivery Systems in Development of Genetic and Subunit Vaccines
Bolhassani, A. (2022) · Molecular Biotechnology · doi:10.1007/s12033-022-00624-8 · Cited by 36
Hellgren, F., Rosdahl, A., Cerveira, R. A., Lenart, K., Ols, S., Gwon, Y.-D., Kurt, S., Delis, A. M., Joas, G., Evander, M., et al. (2024) · JCI Insight · doi:10.1172/jci.insight.175401 · Cited by 32
mRNA-Based Vaccines and Mode of Action
Gergen, J., & Petsch, B. (2020) · Current topics in microbiology and immunology · doi:10.1007/82_2020_230 · Cited by 36
Valentin, A., Bergamaschi, C., Rosati, M., Angel, M., Burns, R., Agarwal, M., Gergen, J., Petsch, B., Oostvogels, L., Loeliger, E., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.945706 · Cited by 32
Bai, S., Yang, T., Zhu, C., Feng, M., Zhang, L., Zhang, Z., Wang, X., Yu, R., Pan, X., Chen, Z., et al. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1099991 · Cited by 31
“Frontiers in Immunology 11 median VNT of 650 IU/ml after two injections in murine models (16).”
BackgroundInfluentialXu, J., Wang, R., Luo, W., Mao, X., Gao, H. Z., Feng, X., Chen, G., Yang, Z., Deng, W., & Nie, Y. (2023) · Acta Biomaterialia · doi:10.1016/j.actbio.2023.12.009 · Cited by 31
The potential use of therapeutics and prophylactic mRNA vaccines in human papillomavirus (HPV)
Movahed, F., Darzi, S., Mahdavi, P., Mahdi, M. S., Allela, O. Q. B., Sameer, H. N., Adil, M., Zarkhah, H., Yasamineh, S., & Gholizadeh, O. (2024) · Virology Journal · doi:10.1186/s12985-024-02397-9 · Cited by 37
“In a similar vein, NHPs that were administered an i.m. vaccination using an mRNA vaccine formulated by LNPs and encoding the rabies virus glycoprotein (RABV-G) generated antibody titers that were stable for one year and capable of being boosted [128].”
BackgroundRahman, M. M., Zhou, N., & Huang, J. (2021) · Vaccines · doi:10.3390/vaccines9030244 · Cited by 32
“Remarkably, the cellular and humoral immunity in NHPs, mediated by LNP/mRNA vaccines, against influenza H3N2 and rabies viruses were superior over licensed Rabipur and Fluad vaccines, respectively [92].”
BackgroundCOVID‐19: Clinical status of vaccine development to date
Kumar, S., Basu, M., Ghosh, P., Ansari, A., & Ghosh, M. K. (2022) · British Journal of Clinical Pharmacology · doi:10.1111/bcp.15552 · Cited by 32
“amino lipids, phospholipids, cholesterol and polyethylene glycol (PEG).(125,127,128)”
BackgroundInfluentialWan, J., Yang, J., Wang, Z., Shen, R., Zhang, C., Wu, Y., Zhou, M., Chen, H., Fu, Z. F., Sun, H., et al. (2023) · Emerging Microbes & Infections · doi:10.1080/22221751.2023.2270081 · Cited by 29
Reducing cell intrinsic immunity to mRNA vaccine alters adaptive immune responses in mice
Wang, Z., Jacobus, E. J., Stirling, D. C., Krumm, S. A., Flight, K. E., Cunliffe, R. F., Mottl, J., Singh, C., Mosscrop, L. G., Santiago, L. A., et al. (2023) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2023.102045 · Cited by 30
“31 Other studies have shown a rapid and sustained cytokine response to mRNA vaccines in mice, 32 with similar elevations in IL-5, IL-6, and MCP-1.”
BackgroundSharifnia, Z., Bandehpour, M., Hamishehkar, H., Mosaffa, N., Kazemi, B., & Zarghami, N. (2019) · PubMed Central · doi:10.22037/ijpr.2019.1100872 · Cited by 26
Current Status of Messenger RNA Delivery Systems
Stanton, M. G. (2018) · Nucleic Acid Therapeutics · doi:10.1089/nat.2018.0726 · Cited by 26
Safety and efficacy assessment of an mRNA rabies vaccine in dogs, rodents, and cynomolgus macaques
Li, J., Yu, P., Liu, Q., Xu, L., Chen, Y., Li, Y., Zhang, F., Zhu, W., & Peng, Y. (2024) · npj Vaccines · doi:10.1038/s41541-024-00925-w · Cited by 24
In the Era of mRNA Vaccines, Is There Any Hope for HIV Functional Cure?
Esteban, I., Pastor-Quiñones, C., Usero, L., Plana, M., García, F., & Leal, L. (2021) · Viruses · doi:10.3390/v13030501 · Cited by 26
“LNPs are a class of particles with different lipid compositions and ratios as well as different sizes and structures formed by different methods [60,61].”
BackgroundClinical advancements in mRNA vaccines against viral infections
Fatima, M. T., Park, P., & Hong, K. (2024) · Clinical Immunology · doi:10.1016/j.clim.2024.110424 · Cited by 25
Oral mRNA Vaccines Against Infectious Diseases- A Bacterial Perspective [Invited]
Jawalagatti, V., Kirthika, P., & Lee, J. H. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.884862 · Cited by 24
mRNA delivery technologies: Toward clinical translation
Gómez-Aguado, I., Rodríguez-Castejón, J., Beraza-Millor, M., Rodríguez‐Gascón, A., del Pozo‐Rodríguez, A., & Solinís, M. Á. (2022) · International review of cytology · doi:10.1016/bs.ircmb.2022.04.010 · Cited by 23
Nonclinical safety evaluation of a novel ionizable lipid for mRNA delivery
Broudic, K., Amberg, A., Schaefer, M. K., Spirkl, H.-P., Bernard, M., & Désert, P. (2022) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2022.116143 · Cited by 25
Roth, N., Schön, J., Hoffmann, D., Thran, M., Thess, A., Mueller, S. O., Petsch, B., & Rauch, S. (2022) · Vaccines · doi:10.3390/vaccines10081251 · Cited by 22
mRNA-Based Approaches to Treating Liver Diseases
Cacicedo, M. L., Limeres, M. J., & Gehring, S. (2022) · Cells · doi:10.3390/cells11203328 · Cited by 23
Advances in modification and delivery of nucleic acid drugs
Wang, J., Tan, M., Wang, Y., Liu, X., & Lin, A. (2023) · Journal of Zhejiang University (Medical Sciences) · doi:10.3724/zdxbyxb-2023-0130 · Cited by 24
The mRNA vaccine, a swift warhead against a moving infectious disease target
Mir, S., & Mir, M. A. (2024) · Expert Review of Vaccines · doi:10.1080/14760584.2024.2320327 · Cited by 28
“For example, CureVac’s protamine-based rabies vaccine candidate CV7201 triggered severe adverse effects in 78% of participants [78], which prompted the use of LNPs as the preferred delivery vehicles for the next vaccine candidate CV7202 [79].”
Next-Generation mRNA Vaccines in Melanoma: Advances in Delivery and Combination Strategies
Zoroddu, S., & Bagella, L. (2025) · Cells · doi:10.3390/cells14181476 · Cited by 28
“Furthermore, the advent of lipid nanoparticle (LNP) delivery systems has overcome a fundamental obstacle to the application of mRNA vaccines, protecting labile RNA from degradation, facilitating cellular uptake, and ensuring efficient endosomal escape [2,10,11].”
An Insight into Nanomedicinal Approaches to Combat Viral Zoonoses
Minakshi, P., Ghosh, M., Kumar, R., Brar, B., Lambe, U. P., Banerjee, S., Ranjan, K., Kumar, B., Goel, P., Malik, Y. S., et al. (2020) · Current Topics in Medicinal Chemistry · doi:10.2174/1568026620666200325114400 · Cited by 21
Better, Faster, Stronger: mRNA Vaccines Show Promise for Influenza Vaccination in Older Adults
Bartley, J. M., Cadar, A. N., & Martin, D. E. (2021) · Immunological Investigations · doi:10.1080/08820139.2021.1909617 · Cited by 21
Du, X., Yada, E., Terai, Y., Takahashi, T., Nakanishi, H., Tanaka, H., Akita, H., & Itaka, K. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15092291 · Cited by 21
Universal influenza virus vaccines: what needs to happen next?
Trucchi, C., Paganino, C., Amicizia, D., Orsi, A., Tisa, V., Piazza, M. F., Icardi, G., & Ansaldi, F. (2019) · Expert Opinion on Biological Therapy · doi:10.1080/14712598.2019.1604671 · Cited by 21
Kyei-Barffour, I., Akwetey, S. A., Aninagyei, E., Ghartey‐Kwansah, G., & Acheampong, D. O. (2021) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2021.112282 · Cited by 21
“Thus, SARS-CoV-2-mRNA vaccines are translated in the cytoplasm to synthesize SARS-CoV-2-antigens which are processed and presented for humoral and T cell immune response activation [111, 112] (Fig.”
Improving the Repeatability and Efficacy of Intradermal Electroporated Self-Replicating mRNA
Huysmans, H., Temmerman, J. D., Zhong, Z., Cafferty, S. M., Combes, F., Haesebrouck, F., & Sanders, N. N. (2019) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2019.06.011 · Cited by 19
“Therefore, a more reliable way of presenting in vivo bioluminescence data is showing all of the individual data points.(11,14,32) However, when using large group samples, graphs often become cluttered, resulting in loss of clarity.”
BackgroundRoth, N., Schön, J., Hoffmann, D., Thran, M., Thess, A., Mueller, S. O., Petsch, B., & Rauch, S. (2021) · doi:10.1101/2021.05.13.443734 · Cited by 18
Dai, W., Xing, M., Sun, L., Lv, L., Wang, X., Wang, Y., Pang, X., Guo, Y., Ren, J., & Zhou, D. (2024) · Journal of Virology · doi:10.1128/jvi.01699-24 · Cited by 22
IL-7 promotes mRNA vaccine-induced long-term immunity
Wang, L., Wan, J., He, W., Wang, Z., Wu, Q. D., Zhou, M., Fu, Z. F., & Zhao, L. (2024) · Journal of Nanobiotechnology · doi:10.1186/s12951-024-02993-5 · Cited by 18
mRNA Vaccines: Current Applications and Future Directions
Li, J., Liu, Y., Dai, J., Li, Y., Xiong, F., Xia, J., Jin, J., Wu, Y., & Peng, X. (2025) · MedComm · doi:10.1002/mco2.70434 · Cited by 27
mRNABERT: advancing mRNA sequence design with a universal language model and comprehensive dataset
Xiong, Y., Wang, A., Kang, Y., Shen, C., Hsieh, C., & Hou, T. (2025) · Nature Communications · doi:10.1038/s41467-025-65340-8 · Cited by 20
Khare, S., Niharika, N., Singh, A., Hussain, I., Singh, N. B., & Singh, S. C. (2022) · Applied Biochemistry and Biotechnology · doi:10.1007/s12010-022-04181-3 · Cited by 16
“the CVnCoV (CureVac) vaccine candidate comprises an “unmodified” mRNA, in which uridine content is reduced by utilizing sequence engineering, selected UTRs, and for the elimination of fragments of dsRNA a stringent purification protocol is followed [89].”
BackgroundMethodBoretti, A. A. (2024) · Clinical and Experimental Medicine · doi:10.1007/s10238-023-01264-1 · Cited by 25
Unlocking the potential of vaccines built on messenger RNA
Dolgin, E. (2019) · Nature · doi:10.1038/d41586-019-03072-8 · Cited by 17
Potential of mRNA-based vaccines for the control of tick-borne pathogens in one health perspective
Cueto, E. G., de la Fuente, J., & López‐Camacho, C. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1384442 · Cited by 16
Revolutionizing mRNA Vaccines Through Innovative Formulation and Delivery Strategies
Fatima, M., An, T., & Hong, K. (2025) · Biomolecules · doi:10.3390/biom15030359 · Cited by 20
Broudic, K., Laurent, S., Perkov, V., Simon, C., Garinot, M., Truchot, N., Latour, J., & Désert, P. (2023) · Journal of Applied Toxicology · doi:10.1002/jat.4548 · Cited by 15
“…in the same LNP vehicle (Broudic et al., 2022), based on the assumption that the safety profile of LNP/mRNA-based vaccines is mainly driven by the LNP component rather than by the mRNA (Hassett et al., 2019; Lutz et al., 2017; Marlowe et al., 2017; Sabnis et al., 2018; Sedic et al., 2018).”
BackgroundHensley, C., Roier, S., Zhou, P., Schnur, S., Nyblade, C., Parreño, V. G., Frazier, A., Frazier, M., Kiley, K., O’Brien, S., et al. (2024) · Vaccines · doi:10.3390/vaccines12030260 · Cited by 14
“An LNP-formulated mRNA encoding rabies virus glycoprotein (RABV-G) served as an irrelevant mRNA vaccine and, thus, as a negative control in the present study [30,31].”
BackgroundPark, S. A., Hwang, D., Kim, J. H., Lee, S.-Y., Lee, J., Kim, H. S., Kim, K., Lim, B., Lee, J., Jeon, Y. H., et al. (2024) · Biomaterials Science · doi:10.1039/d4bm01070a · Cited by 13
Webster, H. S., Valencia, S. M., Kumar, A., Chan, C. C. W., Dennis, M. L., Roark, H. K., Woods, A., John, S. A., Carfı́, A., & Permar, S. R. (2021) · Vaccine · doi:10.1016/j.vaccine.2021.08.011 · Cited by 12
Message in a bottle: mRNA vaccination for influenza
Shartouny, J. R., & Lowen, A. C. (2022) · Journal of General Virology · doi:10.1099/jgv.0.001765 · Cited by 15
“delivered in lipid nanoparticles, showing sustained humoral responses at levels comparable to a licensed inactivated vaccine [29].”
BackgroundRabies vaccine: Recent update and comprehensive review of in vitro and in vivo studies
Abedi, M., Haftcheshmeh, S. M., Bashar, R., Kesharwani, P., Samadi, M., & Sahebkar, A. (2022) · Process Biochemistry · doi:10.1016/j.procbio.2022.11.011 · Cited by 14
Agent-based model of the impact of higher influenza vaccine efficacy on seasonal influenza burden
Krauland, M. G., Zimmerman, R. K., Williams, K. V., Raviotta, J. M., Harrison, L. H., Williams, J. V., & Roberts, M. S. (2022) · Vaccine X · doi:10.1016/j.jvacx.2022.100249 · Cited by 12
Development of mRNA rabies vaccines
Fang, Z., Yu, P., & Zhu, W. (2024) · Human Vaccines & Immunotherapeutics · doi:10.1080/21645515.2024.2382499 · Cited by 16
Atochina‐Vasserman, E. N., Lindesmith, L. C., Mirabelli, C., Ona, N. A., Reagan, E. K., Brewer-Jensen, P. D., Mercado-López, X., Shahnawaz, H., Meshanni, J. A., Baboo, I., et al. (2024) · npj Vaccines · doi:10.1038/s41541-024-00976-z · Cited by 14
Self-citationFix, A. D., Kirkwood, C. D., Steele, A. D., et al. (2020) · Vaccine · doi:10.1016/j.vaccine.2020.11.034 · Cited by 13
Sharifnia, Z., Bandehpour, M., Kazemi, B., & Zarghami, N. (2018) · Iranian Biomedical Journal · doi:10.29252/ibj.23.1.57 · Cited by 18
Determination of significant immunological timescales from mRNA-LNP-based vaccines in humans
Moyles, I. R., Korosec, C. S., & Heffernan, J. M. (2023) · Journal of Mathematical Biology · doi:10.1007/s00285-023-01919-3 · Cited by 11
“This is supported experimentally where Lutz et al (2017), for example, observed that mice began to produce antigen at the site of injection on the order of hours after the needle, while antibody decay halflife was on the order of many days.”
MethodGlobal emergence of SARS-CoV-2 variants: new foresight needed for improved vaccine efficacy
Yadav, P. D., & Kumar, S. (2021) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(21)00687-3 · Cited by 12
Two quality and stability indicating imaged CIEF methods for mRNA vaccines
Krebs, F., Burger, U., Doerks, S., Krämer, M., & Wätzig, H. (2022) · Electrophoresis · doi:10.1002/elps.202200123 · Cited by 14
“The mRNA-LNP (CureVac AG, Tübingen, Germany) used in this study consists of four lipid components: cholesterol, 1,2-distearoyl-sn-glycero-3-phosphocholine, PEGylated lipids, and a cationic lipid (LNP formulation by Acuitas Therapeutics [Vancouver, BC, Canada] [5]).”
MethodAdvances and Strategies in Enhancing mRNA Cancer Vaccines
Zhang, M., Chen, S., Hu, H.-J., Ong, Y., & Ni, Q. (2025) · Advanced Materials · doi:10.1002/adma.202509880 · Cited by 17
Michels, C. A., Perrier, D., Kunadhasan, J., Clark, E., Gehrett, J., Gehrett, B., Kwiatek, K., Adams, S., Chandler, R. W., Stagno, L., et al. (2023) · International Journal of Vaccine Theory Practice and Research · doi:10.56098/ijvtpr.v3i1.85 · Cited by 11
Sharifnia, Z., Bandehpour, M., Kazemi, B., et al. (2019) · PubMed · doi:10.29252/.23.1.57 · Cited by 11
“mRNA vaccines is promising to prevent and treat a wide range of diseases such as influenza, rabies, or cancers [18,20] .”
BackgroundDewani, M., Mamidwar, A., Rawal, M., Nutan, B., Liu, J., Pisal, N. D., Liu, S., Blank, E., Banerjee, A., Park, D., et al. (2026) · Nature Nanotechnology · doi:10.1038/s41565-025-02101-0 · Cited by 13
Preclinical development of an mRNA-based multiepitope immunotherapeutic for glioblastoma
Lutz, J., Feist, R. K., Sonntag, T., Peguero-Sánchez, E., Wolter, K., Bick, R., Bauer, J., Walz, J. S., & Heidenreich, R. (2025) · Cancer Immunology, Immunotherapy · doi:10.1007/s00262-025-04178-x · Cited by 9
“To develop a broadly applicable off-the-shelf mRNA-based immunotherapeutic for GBM, we designed CVGBM, which is based on CureVac’s platform of chemically unmodified mRNA encapsulated in lipid nanoparticles (LNP) [22].”
Self-citationEngstrand, O., Joas, G., Miranda, M. C., Yan, X., Lenart, K., Cerveira, R. A., Reinhardt, A., & Loré, K. (2025) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2025.102588 · Cited by 10
“Nevertheless, sequence-engineered un-modified mRNA has shown good immunogenicity 6,7 and may be applicable as therapeutics for certain diseases such as for cancer treat-ment.”
La nueva generación de vacunas de ARN mensajero (ARNm) frente a la gripe
Reina, J. (2021) · Enfermedades Infecciosas y Microbiología Clínica · doi:10.1016/j.eimc.2021.07.009 · Cited by 11
Immunogenicity of Low-Dose Prime-Boost Vaccination of mRNA Vaccine CV07050101 in Non-Human Primates
van Doremalen, N., Fischer, R. J., Schulz, J. E., Holbrook, M. G., Smith, B. J., Lovaglio, J., Petsch, B., & Munster, V. J. (2021) · Viruses · doi:10.3390/v13081645 · Cited by 9
“The efficaciousness of this platform has been demonstrated for a rabies vaccine in mice and humans [18,22].”
BackgroundThe new generation of messenger RNA (mRNA) vaccines against influenza
Reina, J. (2022) · Enfermedades infecciosas y microbiologia clinica (English ed ) · doi:10.1016/j.eimce.2022.07.006 · Cited by 10
Thran, M., Poenisch, M., Danz, H., Horscroft, N., Ichtchenko, K., Tzipori, S. R., & Shoemaker, C. B. (2023) · Scientific Reports · doi:10.1038/s41598-023-41092-7 · Cited by 11
“In general, lipid nanoparticle formulation was performed with Acuitas therapeutics LNP technology and has been described previously 61 .”
Gebre, M. S., Rauch, S., Roth, N., Yu, J., Chandrashekar, A., Mercado, N. B., He, X., Liu, J., McMahan, K., Martinot, A., et al. (2021) · doi:10.1101/2021.08.13.456316 · Cited by 8
“3 sequence engineered mRNA, without pseudouridine [6-12].”
Significance of VLPs in Vlp-circRNA vaccines: a vaccine candidate or delivery vehicle?
Gupta, R., Arora, K., Arora, N. M., & Kundu, P. K. (2024) · RNA Biology · doi:10.1080/15476286.2024.2399307 · Cited by 11
Zhang, Y., Li, J., Wang, Z., Kuang, Y., Li, S., & Wang, X. (2025) · Animal Diseases · doi:10.1186/s44149-025-00186-7 · Cited by 9
“…is the iteration of CureVac’s COVID-19 vaccine: CV2CoV, which, on the basis of the unmodified RNActive ® technology of CVnCoV, introduced optimized UTRs (5’HSD17B4, 3’PSMB3, histone stem ‒ loop, and poly(A) tail), significantly improving immunogenicity (Lutz et al. 2017; Aldrich et al. 2021).”
Ru, E. C. L., Böttger, R., Andrews, D. T., Baumhof, P., Rakonjac, J. V., Laufersky, G., & Darby, B. L. (2025) · Nano Letters · doi:10.1021/acs.nanolett.5c01491 · Cited by 8
Self-citationWang, J., Wu, K. W., Liu, Y., Wang, S., Li, Z., Zhang, D., Liu, R., Ren, Y., Shao, S., & Liu, Q. (2025) · npj Vaccines · doi:10.1038/s41541-025-01222-w · Cited by 8
Recent Developments of RNA Vaccines and Therapeutics: Reagents, Formulations, and Characterization
Tomeh, M. A., Smith, R. K., & Watkinson, A. (2025) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.5c00670 · Cited by 8
Musa, H. H., & Musa, T. H. (2022) · Human Vaccines & Immunotherapeutics · doi:10.1080/21645515.2022.2135927 · Cited by 11
Vosoughi, P., Naghib, S. M., Rahmanian, M., & Mozafari, M. R. (2025) · Current Topics in Medicinal Chemistry · doi:10.2174/0115680266325847241121034100 · Cited by 7
Immunology of biodegradable nanoparticles: a brief overview on a wide growing field
Pisani, A., & Bardi, G. (2021) · Exploration of Immunology · doi:10.37349/ei.2021.00006 · Cited by 7
“As well as for liposomes, major interest is reserved to SLNPs to improve the stability of mRNA and siRNA vaccine formulation [87].”
BackgroundRecent and advanced nano-technological strategies for COVID-19 vaccine development
Nwagwu, C. S., Ugwu, C. N., Ogbonna, J. D., Onugwu, A. L., Agbo, C. P., Echezona, A. C., Ezeibe, E. N., Uzondu, S. W., Kenechukwu, F. C., Akpa, P. A., et al. (2022) · Methods in microbiology · doi:10.1016/bs.mim.2022.03.001 · Cited by 7
Research and Patents on Coronavirus and COVID-19: A Review
Aranda, P., Wicklein, B., Ruiz‐García, C., Martín‐Sampedro, R., Darder, M., del Real, G., & Ruiz‐Hitzky, E. (2020) · Recent Patents on Nanotechnology · doi:10.2174/1872210514666201021145735 · Cited by 8
Literature Mining and Mechanistic Graphical Modelling to Improve mRNA Vaccine Platforms
Leonardelli, L., Lofano, G., Selvaggio, G., Parolo, S., Giampiccolo, S., Tomasoni, D., Domenici, E., Priami, C., Song, H., Medini, D., et al. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.738388 · Cited by 9
Modified mRNA-Based Vaccines Against Coronavirus Disease 2019
Wang, A. Y. L. (2022) · Cell Transplantation · doi:10.1177/09636897221090259 · Cited by 7
A mRNA-LNP vaccine against Dengue Virus elicits robust, serotype-specific immunity
Wollner, C. J., Richner, M., Hassert, M. A., Pinto, A. K., Brien, J. D., & Richner, J. M. (2021) · doi:10.1101/2021.01.05.425517 · Cited by 6
“mRNA vaccines have also been shown to provide protective immunity against viral 103 pathogens in non-human primates(25, 26).”
BackgroundAhmadi, S., Amirzadeh, M., Ahmadi, M., & Soleiman-Meigooni, S. (2024) · Journal of Tropical Medicine · doi:10.1155/jotm/6688914 · Cited by 6
Toyonaga, H., Arai, K., Zhang, M., Cheng, L., & Tanaka, H. (2025) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2025.102592 · Cited by 7
Cnossen, V. M., Moreira, P. C. L., Engelhardt, O. G., et al. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1568778 · Cited by 6
Pascolo, S. (2023) · European Journal of Immunology · doi:10.1002/eji.202249941 · Cited by 6
Controlling Protein Expression by Delivery of RNA Therapeutics Using Lipid Nanoparticles
Lin, P. J. C., & Tam, Y. K. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-814470-1.00009-5 · Cited by 6
Self-citationSARS-CoV-2 mRNA vaccine is re-adenylated in vivo , enhancing antigen production and immune responsePreprint
Krawczyk, P. S., Gewartowska, O., Mazur, M., Orzeł, W., Matylla-Kulińska, K., Jeleń, S., Turowski, P., Śpiewla, T., Tarkowski, B., Tudek, A., et al. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.12.01.518149 · Cited by 5
Recent Advances in mRNA Vaccine DevelopmentPreprint
Aga, A. M., Kelel, M., & Gemeda, M. T. (2023) · Preprints.org · doi:10.20944/preprints202308.0245.v1 · Cited by 5
Nanoparticle-Based Vaccines against Zoonotic Viruses: A Review
Zhang, X., & Cui, Z. (2023) · Zoonoses · doi:10.15212/zoonoses-2023-0018 · Cited by 6
“It was found that a new type of mRNA-LNP formulation containing the RABV-G mRNA antigen elicits immune responses in non-human primates comparable to those induced by licensed vaccines [78].”
BackgroundMessenger ribonucleic acid vaccines for severe acute respiratory syndrome coronavirus-2 – a review
Akamine, C. M., & Sahly, H. M. E. (2021) · Translational research · doi:10.1016/j.trsl.2021.12.007 · Cited by 5
“Nonhuman primates who received an LNP-complexed mRNA vaccine against influenza were demonstrated to have equivalent antibodies following 1 dose as compared with an adjuvanted subunit influenza vaccine, higher antibody responses after the second LNPmRNA dose.(29) In rhesus macaques, vaccination with LNP-mRNA compared t…”
BackgroundResultApplication of Nanotechnology in COVID-19 Infection: Findings and Limitations
Shehu, I. A., Musa, M. K., Datta, A., & Verma, A. (2022) · Journal of Nanotheranostics · doi:10.3390/jnt3040014 · Cited by 5
Metadata
- Authors
- Lutz, J., Lazzaro, S., Habbeddine, M., Schmidt, K. E., Baumhof, P., Mui, B. L., Tam, Y. K., Madden, T. D., Hope, M. J., Heidenreich, R., & Fotin-Mleczek, M.
- Affiliations
- CureVac (Germany) (DE)
- Acuitas Therapeutics (Canada) (CA)
- Venue
- npj Vaccines
- Published
- 2017-10-19
- Volume
- 2
- Issue
- 1
- Pages
- 29-29
- ISSN
- 2059-0105 (ISSN-L)
- PMC
- PMC5648897
- OpenAlex
- W2761745911
- Cited by
- 257
- References
- 36
- Citations by year
- 2026: 13 · 2025: 25 · 2024: 39 · 2023: 39 · 2022: 41 · 2021: 51 · 2020: 26 · 2019: 14 · 2018: 9
- FWCI
- 4.77
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- npj Vaccines (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (submittedVersion, cc-by)
- PubMed Central (submittedVersion, cc-by)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Keywords
- mRNA vaccines, lipid nanoparticles, rabies vaccine, influenza vaccination, prophylactic vaccination, non-human primates, intramuscular vaccination, antibody response, T cell response, innate immune activation, draining lymph nodes, cytokines and chemokines, sequential vaccination, vaccine platforms
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-11, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-11 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
