mRNA vaccines encoding influenza virus hemagglutinin (HA) elicits immunity in mice from influenza A virus challenge

PLoS One. 2024 Apr 18;19(4):e0297833. doi: 10.1371/journal.pone.0297833. eCollection 2024.

Abstract

Influenza viruses cause epidemics and can cause pandemics with substantial morbidity with some mortality every year. Seasonal influenza vaccines have incomplete effectiveness and elicit a narrow antibody response that often does not protect against mutations occurring in influenza viruses. Thus, various vaccine approaches have been investigated to improve safety and efficacy. Here, we evaluate an mRNA influenza vaccine encoding hemagglutinin (HA) proteins in a BALB/c mouse model. The results show that mRNA vaccination elicits neutralizing and serum antibodies to each influenza virus strain contained in the current quadrivalent vaccine that is designed to protect against four different influenza viruses including two influenza A viruses (IAV) and two influenza B (IBV), as well as several antigenically distinct influenza virus strains in both hemagglutination inhibition assay (HAI) and virus neutralization assays. The quadrivalent mRNA vaccines had antibody titers comparable to the antibodies elicited by the monovalent vaccines to each tested virus regardless of dosage following an mRNA booster vaccine. Mice vaccinated with mRNA encoding an H1 HA had decreased weight loss and decreased lung viral titers compared to mice not vaccinated with an mRNA encoding an H1 HA. Overall, this study demonstrates the efficacy of mRNA-based seasonal influenza vaccines are their potential to replace both the currently available split-inactivated, and live-attenuated seasonal influenza vaccines.

MeSH terms

  • Animals
  • Antibodies, Viral
  • Hemagglutinin Glycoproteins, Influenza Virus / genetics
  • Hemagglutinins
  • Humans
  • Influenza A virus*
  • Influenza Vaccines*
  • Influenza, Human* / prevention & control
  • Mice
  • Orthomyxoviridae Infections*
  • RNA, Messenger / genetics
  • mRNA Vaccines

Substances

  • Influenza Vaccines
  • Hemagglutinins
  • mRNA Vaccines
  • Antibodies, Viral
  • Hemagglutinin Glycoproteins, Influenza Virus
  • RNA, Messenger

Grants and funding

Immorna provided support in the form of salaries for author Z. Beau Reneer but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.