Development of multivalent mRNA vaccine candidates for seasonal or pandemic influenza
Open accessAbstract
Recent approval of mRNA vaccines for emergency use against COVID-19 is likely to promote rapid development of mRNA-based vaccines targeting a wide range of infectious diseases. Compared to conventional approaches, this vaccine modality promises comparable potency while substantially accelerating the pace of development and deployment of vaccine doses. Already demonstrated successfully for single antigen vaccines such as for COVID-19, this technology could be optimized for complex multi-antigen vaccines. Herein, utilizing multiple influenza antigens, we demonstrated the suitability of the mRNA therapeutic (MRT) platform for such applications. Seasonal influenza vaccines have three or four hemagglutinin (HA) antigens of different viral subtypes. In addition, influenza neuraminidase (NA), a tetrameric membrane protein, is identified as an antigen that has been linked to protective immunity against severe viral disease. We detail the efforts in optimizing formulations of influenza candidates that use unmodified mRNA encoding full-length HA or full-length NA encapsulated in lipid nanoparticles (LNPs). HA and NA mRNA-LNP formulations, either as monovalent or as multivalent vaccines, induced strong functional antibody and cellular responses in non-human primates and such antigen-specific antibody responses were associated with protective efficacy against viral challenge in mice.
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Multivalent influenza and cytomegalovirus mRNA vaccines have shown that integration of multiple antigens can lead to robust nAb responses in pre-clinical models which correlate with protection for multiple vaccines.
“Multivalent influenza21 and cytomegalovirus22 mRNA vaccines have shown that integration of multiple antigens can lead to robust nAb responses in pre-clinical models which correlate with protection for multiple vaccines18,23.”
From Efficacy of an unmodified bivalent mRNA vaccine against SARS-CoV-2 variants in female small animal models (2023) · cites this paper as [21]
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- Authors
- Chivukula, S., Plitnik, T., Tibbitts, T., Karve, S., Dias, A., Zhang, D., Goldman, R., Gopani, H., Khanmohammed, A., Sarode, A., Cooper, D., Yoon, H., Kim, Y., Yan, Y., Mundle, S. T., Groppo, R., Beauvais, A., Zhang, J., Anosova, N. G., Lai, C., Li, L., Ulinski, G., Piepenhagen, P., DiNapoli, J., Kalnin, K. V., Landolfi, V., Swearingen, R., Fu, T.-M., DeRosa, F., & Casimiro, D.
- Affiliations
- Emergent BioSolutions (United States) (US)
- Translate Bio (United States) (US)
- Seqirus (United States) (US)
- The University of Texas Health Science Center at Houston (US)
- Sanofi (France) (FR)
- Corresponding author
- Chivukula, Sudha
- ORCID
- Venue
- npj Vaccines
- Published
- 2021-12-16
- Volume
- 6
- Issue
- 1
- Pages
- 153-153
- ISSN
- 2059-0105 (ISSN-L)
- PMC
- PMC8677760
- OpenAlex
- W4200068373
- Cited by
- 117
- References
- 55
- Citations by year
- 2026: 15 · 2025: 27 · 2024: 33 · 2023: 25 · 2022: 17
- FWCI
- 13.51
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- npj Vaccines (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Sanofi
- Sanofi Pasteur
- 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
- influenza vaccination, seasonal influenza, pandemic influenza, hemagglutinin, neuraminidase, lipid nanoparticles, non-human primates, antibody response, cell-mediated immunity, vaccine protection
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