Protective efficacy of in vitro synthesized, specific mRNA vaccines against influenza A virus infection
Abstract
Despite substantial improvements, influenza vaccine production-and availability-remain suboptimal. Influenza vaccines based on mRNA may offer a solution as sequence-matched, clinical-grade material could be produced reliably and rapidly in a scalable process, allowing quick response to the emergence of pandemic strains. Here we show that mRNA vaccines induce balanced, long-lived and protective immunity to influenza A virus infections in even very young and very old mice and that the vaccine remains protective upon thermal stress. This vaccine format elicits B and T cell-dependent protection and targets multiple antigens, including the highly conserved viral nucleoprotein, indicating its usefulness as a cross-protective vaccine. In ferrets and pigs, mRNA vaccines induce immunological correlates of protection and protective effects similar to those of a licensed influenza vaccine in pigs. Thus, mRNA vaccines could address substantial medical need in the area of influenza prophylaxis and the broader realm of anti-infective vaccinology.
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Non-replicating mRNA vaccines using exclusively unmodified nucleosides are immunogenic and capable of inducing protection against lethal rabies and influenza virus infections after intradermal vaccination in mice, rats, ferrets, and pigs.
“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”
From Unmodified mRNA in LNPs constitutes a competitive technology for prophylactic vaccines (2017) · cites this paper as [8]
The prior unmodified mRNA vaccine approach was specifically optimized for intradermal administration and showed lower efficacy when given by the intramuscular route.
“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.”
From Unmodified mRNA in LNPs constitutes a competitive technology for prophylactic vaccines (2017) · cites this paper as [8]
Previously, i.d. administration of protamine-formulated prophylactic mRNA vaccines based on unmodified nucleosides protected mice against influenza or rabies challenge infections and induced strong humoral responses in ferrets and pigs.
“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”
From Unmodified mRNA in LNPs constitutes a competitive technology for prophylactic vaccines (2017) · cites this paper as [8]
Both CVnCoV and CV2CoV are based on RNActive technology and consist of non-chemically modified sequence-engineered mRNA without pseudouridine.
“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 [11]
Several studies have demonstrated the utility of mRNA as the basis of vaccines in cancer immunotherapy as well as to promote prophylactic protection from infectious diseases.
“Several studies have demonstrated the utility of mRNA as the basis of vaccines in cancer immunotherapy as well as to promote prophylactic protection from infectious diseases (Hoerr et al, 2000; Fotin‐Mleczek et al, 2011; Petsch et al, 2012; Kubler et al, 2015; Kranz et al, 2016).”
From mRNA mediates passive vaccination against infectious agents, toxins, and tumors (2017) · cites this paper as Petsch et al, 2012
It has been demonstrated that mRNA active vaccination can use both the intramuscular as well as the intravenous route (Petsch et al, 2012; Kranz et al, 2016).
“It has been demonstrated that mRNA active vaccination can use both the intramuscular as well as the intravenous route (Petsch et al, 2012; Kranz et al, 2016).”
From mRNA mediates passive vaccination against infectious agents, toxins, and tumors (2017) · cites this paper as Petsch et al, 2012
VN titers of ≥0.5 IU/ml are considered protective in humans, dogs and cats.
“considered as protective in humans, dogs and cats [34].”
In the first demonstration of an effective mRNA vaccine against influenza in 2012, three intradermal injections of 80 μg RNActive-mRNA encoding haemagglutinin from the PR8 H1N1 strain induced homologous and heterologous immunity against H1N1 and H5N1 strains, respectively, and protected the mice against a lethal viral dose (10× LD50).
“In the first demonstration of an effective mRNA vaccine against influenza in 2012, three intradermal injections of 80 µg RNActive-mRNA encoding haemagglutinin from the PR8 H1N1 strain induced homologous and heterologous immunity against H1N1 and H5N1 strains, respectively, and protected the mice against a lethal viral dose (10× LD50)141.”
From mRNA vaccines for infectious diseases: principles, delivery and clinical translation (2021) · cites this paper as [141]
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“2 IU/ml), considered as protective in humans, dogs and cats [34].”
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Self-citation
- Authors
- Petsch, B., Schnee, M., Vogel, A. B., Lange, E., Hoffmann, B., Voss, D., Schlake, T., Thess, A., Kallen, K.-J., Stitz, L., & Kramps, T.
- Affiliations
- Friedrich-Loeffler-Institut (DE)
- CureVac (Germany) (DE)
- Corresponding author
- Kallen, Karl-Josef
- Stitz, Lothar
- Venue
- Nature Biotechnology
- Published
- 2012-11-25
- Volume
- 30
- Issue
- 12
- Pages
- 1210-1216
- ISSN
- 0733-222X (ISSN-L)
- 1087-0156
- 1546-1696
- OpenAlex
- W2054298563
- Cited by
- 461
- References
- 47
- Citations by year
- 2026: 13 · 2025: 34 · 2024: 41 · 2023: 45 · 2022: 54 · 2021: 71 · 2020: 40 · 2019: 24 · 2018: 30 · 2017: 26 · 2016: 24 · 2015: 21 · 2014: 16 · 2013: 19 · 2012: 2
- FWCI
- 12.55
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Biotechnology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Epidemiology › Influenza Virus Research Studies
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
- Keywords
- mRNA vaccines, influenza A virus, vaccine production, cross-protective immunity, viral nucleoprotein, immunological correlates of protection, ferrets, pigs, thermal stress (biology), pandemic influenza preparedness, influenza prevention
- MeSH terms
- Aging, Animals, Animals, Newborn, B-Lymphocytes, Biotechnology, Female, Ferrets, Humans, Influenza Vaccines, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Inbred DBA, Molecular Sequence Data, Orthomyxoviridae Infections, Influenza A virus, Rats, Inbred Lew, RNA, Messenger, RNA, Viral, T-Lymphocytes, Vaccines, Synthetic, Sus scrofa, Mice, Rats, Cross Protection
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