Protective efficacy of in vitro synthesized, specific mRNA vaccines against influenza A virus infection

Nat Biotechnol. 2012 Dec;30(12):1210-6. doi: 10.1038/nbt.2436. Epub 2012 Nov 25.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / immunology
  • Animals
  • Animals, Newborn
  • B-Lymphocytes / immunology
  • Biotechnology
  • Cross Protection
  • Female
  • Ferrets
  • Humans
  • Influenza A virus / genetics*
  • Influenza A virus / immunology*
  • Influenza Vaccines / genetics*
  • Influenza Vaccines / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Molecular Sequence Data
  • Orthomyxoviridae Infections / immunology
  • Orthomyxoviridae Infections / prevention & control
  • RNA, Messenger / genetics*
  • RNA, Messenger / immunology*
  • RNA, Viral / genetics
  • RNA, Viral / immunology
  • Rats
  • Rats, Inbred Lew
  • Sus scrofa
  • T-Lymphocytes / immunology
  • Vaccines, Synthetic / genetics
  • Vaccines, Synthetic / immunology


  • Influenza Vaccines
  • RNA, Messenger
  • RNA, Viral
  • Vaccines, Synthetic

Associated data

  • GENBANK/ABD95991
  • GENBANK/ABO21709
  • GENBANK/ABO21710
  • GENBANK/ABO21711
  • GENBANK/ACU65077
  • GENBANK/ACV82259
  • GENBANK/CAZ65588
  • GENBANK/CAZ65589