Preclinical and clinical demonstration of immunogenicity by mRNA vaccines against H10N8 and H7N9 influenza viruses
Open accessAbstract
Recently, the World Health Organization confirmed 120 new human cases of avian H7N9 influenza in China resulting in 37 deaths, highlighting the concern for a potential pandemic and the need for an effective, safe, and high-speed vaccine production platform. Production speed and scale of mRNA-based vaccines make them ideally suited to impede potential pandemic threats. Here we show that lipid nanoparticle (LNP)-formulated, modified mRNA vaccines, encoding hemagglutinin (HA) proteins of H10N8 (A/Jiangxi-Donghu/346/2013) or H7N9 (A/Anhui/1/2013), generated rapid and robust immune responses in mice, ferrets, and nonhuman primates, as measured by hemagglutination inhibition (HAI) and microneutralization (MN) assays. A single dose of H7N9 mRNA protected mice from a lethal challenge and reduced lung viral titers in ferrets. Interim results from a first-in-human, escalating-dose, phase 1 H10N8 study show very high seroconversion rates, demonstrating robust prophylactic immunity in humans. Adverse events (AEs) were mild or moderate with only a few severe and no serious events. These data show that LNP-formulated, modified mRNA vaccines can induce protective immunogenicity with acceptable tolerability profiles.
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Induction of protective immune responses against two different influenza strains could be demonstrated after intramuscular administration in non-human primates and humans using LNP-formulated mRNA vaccines based on chemically modified nucleosides.
“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”
From Unmodified mRNA in LNPs constitutes a competitive technology for prophylactic vaccines (2017) · cites this paper as [15]
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredRecent 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, and immunogenicity for influenza HA strains H10N8 and H7N9 after i.m. administration in NHPs and humans.
“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”
From Unmodified mRNA in LNPs constitutes a competitive technology for prophylactic vaccines (2017) · cites this paper as [15]
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredChemically modified nucleosides have been used in recent publications to reach sufficient antigen expression.
“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”
From Unmodified mRNA in LNPs constitutes a competitive technology for prophylactic vaccines (2017) · cites this paper as [15]
The expression pattern was similar to results from other LNP formulations.
“which was similar to the results from other LNP formulations (Bahl et al., 2017; Pardi et al., 2015).”
From A thermostable mRNA vaccine against COVID-19 (2020) · cites this paper as Bahl et al., 2017
Another 20 years later, mRNA vaccines against infectious disease were investigated in phase I proof-of-concept clinical trials.
“Another 20 years later, mRNA vaccines against infectious disease were investigated in phase I, proof-of-concept, clinical trials.23,24”
From COVID-19 mRNA vaccines: Platforms and current developments (2022) · cites this paper as [24]
In two separate phase I trials in 2016, Moderna evaluated two influenza candidates dosed via two intramuscular injections of lipid nanoparticles encapsulating nucleoside-modified mRNA expressing full-length haemagglutinin from H10N8 and H7N9.
“In two separate phase I trials in 2016, Moderna evaluated two influenza candidates. These vaccines were dosed via two intramuscular injections of LNPs encapsulating nucleoside-modified mRNA expressing full-length haemagglutinin from H10N8 and H7N9 (Table 1).”
From mRNA vaccines for infectious diseases: principles, delivery and clinical translation (2021) · cites this paper as [147]
Both Moderna influenza candidates produced excellent seroconversion and seroprotection.
“Both produced excellent seroconversion and seroprotection147.”
From mRNA vaccines for infectious diseases: principles, delivery and clinical translation (2021) · cites this paper as [147]
Both i.m. and i.d. administration of lipid nanoparticle-mRNA vaccines produce robust immune responses at a well-tolerated dose in human trials.
“Indeed, both i.m. and i.d. administration of lipid nanoparticle–mRNA vaccines produce robust immune responses at a well-tolerated dose in human trials156,157.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [156]
Haemagglutinin is an essential surface antigen of influenza viruses.
“Haemagglutinin is an essential surface antigen of influenza viruses156,157.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [156]
A 50-μg dose level resulted in 96.3% (HAI) and 100% (MN) seroconversion for H7N9.
“A 100-μg dose level induced 78.3% (HAI) and 87.0% (MN) seroconversion for H10N8 (refs156,157) and a 50-μg dose level resulted in 96.3% (HAI) and 100% (MN) seroconversion for H7N9 (refs156,157).”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [156]
A 100-μg dose level induced 78.3% (HAI) and 87.0% (MN) seroconversion for H10N8.
“A 100-μg dose level induced 78.3% (HAI) and 87.0% (MN) seroconversion for H10N8 (refs156,157) and a 50-μg dose level resulted in 96.3% (HAI) and 100% (MN) seroconversion for H7N9 (refs156,157).”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [156]
Lipid nanoparticle-mRNA vaccines are being investigated as influenza vaccines, with some formulations in clinical trials.
“Lipid nanoparticle–mRNA vaccines are also being investigated as influenza vaccines29,41,156,157,159,184,189–191, with some formulations in clinical trials (Table 1).”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [156]
The mRNA-1440 and mRNA-1851 vaccines, composed of lipid nanoparticles and mRNA encoding haemagglutinin from H10N8 and H7N9 influenza viruses, respectively, have completed phase I clinical studies.
“The mRNA-1440 and mRNA-1851 vaccines, which are composed of lipid nanoparticles and mRNA encoding haemagglutinin from H10N8 and H7N9 influenza viruses, respectively, have completed phase I clinical studies (NCT03076385 and NCT03345043)156,157.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [156]
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“injection, robust protein expression was readily detected in the muscle tissue at the injection site, and the most predominant expression was seen in the liver (Figures 2A and 2B), which was similar to the results from other LNP formulations (Bahl et al., 2017; Pardi et al., 2015).”
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- Authors
- Bahl, K., Senn, J. J., Yuzhakov, O., Bulychev, A., Brito, L. A., Hassett, K. J., Laska, M. E., Smith, M., Almarsson, Ö., Thompson, J., Ribeiro, A. (., Watson, M., Zaks, T., & Ciaramella, G.
- Affiliations
- Moderna Therapeutics (United States) (US)
- Corresponding author
- Ciaramella, Giuseppe
- Venue
- Molecular Therapy
- Publisher
- Elsevier BV
- Published
- 2017-06
- Volume
- 25
- Issue
- 6
- Pages
- 1316-1327
- ISSN
- 1525-0016 (ISSN-L)
- PMC
- PMC5475249
- OpenAlex
- W2609075891
- Cited by
- 642
- References
- 55
- Citations by year
- 2026: 27 · 2025: 54 · 2024: 75 · 2023: 80 · 2022: 107 · 2021: 113 · 2020: 78 · 2019: 52 · 2018: 36 · 2017: 19 · 2014: 1
- FWCI
- 39.64
- Type
- journal article
- Language
- en
- Update notices
- erratum (2022-08-03)
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Molecular Therapy (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Epidemiology › Influenza Virus Research Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Keywords
- mRNA vaccines, H7N9 avian influenza, lipid nanoparticle formulation, modified mRNA, hemagglutinin, immunogenicity, vaccine safety, hemagglutination inhibition, microneutralization, ferrets, non-human primates, pandemic influenza preparedness, seroconversion
- MeSH terms
- Animals, Antibodies, Viral, Cell Line, Disease Models, Animal, Female, Ferrets, Humans, Immunization, Immunization Schedule, Influenza Vaccines, Macaca fascicularis, Male, Orthomyxoviridae Infections, Protamines, RNA, Messenger, RNA, Viral, Tissue Distribution, Gene Expression, Mice, Influenza A Virus, H7N9 Subtype, Influenza A Virus, H10N8 Subtype
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