Shattock, A. J. et al. Contribution of vaccination to improved survival and health: modelling 50 years of the Expanded Programme on Immunization. Lancet 403, 2307–2316 (2024).

Article  PubMed  PubMed Central  Google Scholar 

Pollard, A. J. & Bijker, E. M. A guide to vaccinology: from basic principles to new developments. Nat. Rev. Immunol. 21, 83–100 (2021).

Article  CAS  PubMed  Google Scholar 

Freyn, A. W. et al. A multi-targeting, nucleoside-modified mRNA influenza virus vaccine provides broad protection in mice. Mol. Ther. 28, 1569–1584 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

John, S. et al. Multi-antigenic human cytomegalovirus mRNA vaccines that elicit potent humoral and cell-mediated immunity. Vaccine 36, 1689–1699 (2018).

Article  CAS  PubMed  Google Scholar 

McMahon, M. et al. Assessment of a quadrivalent nucleoside-modified mRNA vaccine that protects against group 2 influenza viruses. Proc. Natl Acad. Sci. USA 119, e2206333119 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Pardi, N. et al. Development of a pentavalent broadly protective nucleoside-modified mRNA vaccine against influenza B viruses. Nat. Commun. 13, 4677 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sajid, A. et al. mRNA vaccination induces tick resistance and prevents transmission of the Lyme disease agent. Sci. Transl. Med. 13, eabj9827 (2021).

Article  CAS  PubMed  Google Scholar 

Arevalo, C. P. et al. A multivalent nucleoside-modified mRNA vaccine against all known influenza virus subtypes. Science 378, 899–904 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Tseng, H. F. et al. mRNA-1273 bivalent (original and Omicron) COVID-19 vaccine effectiveness against COVID-19 outcomes in the United States. Nat. Commun. 14, 5851 (2023).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Harris, E. Combined COVID-19, flu vaccine candidate headed to phase 3 trials. JAMA 330, 2044 (2023).

PubMed  Google Scholar 

Ye, Q. et al. Rational development of a combined mRNA vaccine against COVID-19 and influenza. NPJ Vaccines 7, 84 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Daniel, S., Kis, Z., Kontoravdi, C. & Shah, N. Quality by design for enabling RNA platform production processes. Trends Biotechnol. 40, 1213–1228 (2022).

Article  CAS  PubMed  Google Scholar 

Warne, N. et al. Delivering 3 billion doses of Comirnaty in 2021. Nat. Biotechnol. 41, 183–188 (2023).

CAS  PubMed  Google Scholar 

Alameh, M. G., Weissman, D. & Pardi, N. Messenger RNA-based vaccines against infectious diseases. Curr. Top. Microbiol. Immunol. 440, 111–145 (2022).

PubMed  Google Scholar 

Blakney, A. K., Ip, S. & Geall, A. J. An update on self-amplifying mRNA vaccine development. Vaccines 9, 97 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lutz, J. et al. Unmodified mRNA in LNPs constitutes a competitive technology for prophylactic vaccines. NPJ Vaccines 2, 29 (2017).

Article  PubMed  PubMed Central  Google Scholar 

Petsch, B. et al. Protective efficacy of in vitro synthesized, specific mRNA vaccines against influenza A virus infection. Nat. Biotechnol. 30, 1210–1216 (2012). The first published paper demonstrating that a directly injected, non-replicating mRNA vaccine can induce protective immune responses against a viral pathogen.

Article  CAS  PubMed  Google Scholar 

Rauch, S. et al. mRNA-based SARS-CoV-2 vaccine candidate CVnCoV induces high levels of virus-neutralising antibodies and mediates protection in rodents. NPJ Vaccines 6, 57 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kremsner, P. G. et al. Efficacy and safety of the CVnCoV SARS-CoV-2 mRNA vaccine candidate in ten countries in Europe and Latin America (HERALD): a randomised, observer-blinded, placebo-controlled, phase 2b/3 trial. Lancet Infect. Dis. 22, 329–340 (2022).

Article  CAS  PubMed  Google Scholar 

Baden, L. R. et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N. Engl. J. Med. 384, 403–416 (2021). Along with Polack et al. (2020), the first report about the results of a large phase III clinical trial with an mRNA vaccine.

Article  CAS  PubMed  Google Scholar 

Polack, F. P. et al. Safety and efficacy of the BNT162b2 mRNA covid-19 vaccine. N. Engl. J. Med. 383, 2603–2615 (2020). Along with Baden et al. (2021), the first report about the results of a large phase III clinical trial with an mRNA vaccine.

Article  CAS  PubMed  Google Scholar 

Kariko, K., Buckstein, M., Ni, H. & Weissman, D. Suppression of RNA recognition by Toll-like receptors: the impact of nucleoside modification and the evolutionary origin of RNA. Immunity 23, 165–175 (2005). The first report showing that nucleoside modification of IVT mRNA decreases its inflammatory capacity.

Article  CAS  PubMed  Google Scholar 

Kariko, K. et al. Incorporation of pseudouridine into mRNA yields superior nonimmunogenic vector with increased translational capacity and biological stability. Mol. Ther. 16, 1833–1840 (2008). The first report demonstrating that the introduction of modified nucleosides to the IVT mRNA increases its translatability.

Article  CAS  PubMed  Google Scholar 

Chaudhary, N., Weissman, D. & Whitehead, K. A. mRNA vaccines for infectious diseases: principles, delivery and clinical translation. Nat. Rev. Drug Discov. 20, 817–838 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Metkar, M., Pepin, C. S. & Moore, M. J. Tailor made: the art of therapeutic mRNA design. Nat. Rev. Drug Discov. 23, 67–83 (2024).

Article  CAS  PubMed  Google Scholar 

Pardi, N., Hogan, M. J., Porter, F. W. & Weissman, D. mRNA vaccines — a new era in vaccinology. Nat. Rev. Drug Discov. 17, 261–279 (2018).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Verbeke, R., Hogan, M. J., Lore, K. & Pardi, N. Innate immune mechanisms of mRNA vaccines. Immunity 55, 1993–2005 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Henderson, J. M. et al. Cap 1 messenger RNA synthesis with co-transcriptional CleanCap(R) analog by in vitro transcription. Curr. Protoc. 1, e39 (2021).

Article  CAS  PubMed  Google Scholar 

Pardi, N., Muramatsu, H., Weissman, D. & Kariko, K. In vitro transcription of long RNA containing modified nucleosides. Methods Mol. Biol. 969, 29–42 (2013).

Article  CAS  PubMed  Google Scholar 

Abbas, Y. M. et al. Structure of human IFIT1 with capped RNA reveals adaptable mRNA binding and mechanisms for sensing N1 and N2 ribose 2′-O methylations. Proc. Natl Acad. Sci. USA 114, E2106–E2115 (2017).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Castillo-Hair, S. M. & Seelig, G. Machine learning for designing next-generation mRNA therapeutics. Acc. Chem. Res. 55, 24–34 (2022).

Article  CAS