mRNA vaccines encoding computationally optimized hemagglutinin elicit protective antibodies against future antigenically drifted H1N1 and H3N2 influenza viruses isolated between 2018-2020

Front Immunol. 2024 Mar 12:15:1334670. doi: 10.3389/fimmu.2024.1334670. eCollection 2024.

Abstract

Background: The implementation of mRNA vaccines against COVID-19 has successfully validated the safety and efficacy of the platform, while at the same time revealing the potential for their applications against other infectious diseases. Traditional seasonal influenza vaccines often induce strain specific antibody responses that offer limited protection against antigenically drifted viruses, leading to reduced vaccine efficacy. Modern advances in viral surveillance and sequencing have led to the development of in-silico methodologies for generating computationally optimized broadly reactive antigens (COBRAs) to improve seasonal influenza vaccines.

Methods: In this study, immunologically naïve mice were intramuscularly vaccinated with mRNA encoding H1 and H3 COBRA hemagglutinins (HA) or wild-type (WT) influenza HAs encapsulated in lipid nanoparticles (LNPs).

Results: Mice vaccinated with H1 and H3 COBRA HA-encoding mRNA vaccines generated robust neutralizing serum antibody responses against more antigenically distinct contemporary and future drifted H1N1 and H3N2 influenza strains than those vaccinated with WT H1 and H3 HA-encoding mRNA vaccines. The H1 and H3 COBRA HA-encoding mRNA vaccines also prevented influenza illness, including severe disease in the mouse model against H1N1 and H3N2 viruses.

Conclusions: This study highlights the potential benefits of combining universal influenza antigen design technology with modern vaccine delivery platforms and exhibits how these vaccines can be advantageous over traditional WT vaccine antigens at eliciting superior protective antibody responses against a broader number of influenza virus isolates.

Keywords: H1N1; H3N2; hemagglutinin; influenza; mRNA; universal; vaccine.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • COVID-19 Vaccines
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Hemagglutinins
  • Humans
  • Influenza A Virus, H1N1 Subtype*
  • Influenza A Virus, H3N2 Subtype
  • Influenza Vaccines*
  • Influenza, Human*
  • Mice
  • Orthomyxoviridae Infections*
  • mRNA Vaccines

Substances

  • Influenza Vaccines
  • Hemagglutinins
  • mRNA Vaccines
  • COVID-19 Vaccines
  • Antibodies, Viral
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Antibodies, Neutralizing

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This project has been funded as part of the Collaborative Influenza Vaccine Innovations Centers (CIVICs) by the National Institute of Allergy and Infectious Diseases, a component of the NIH, Department of Health and Human Services, under contract 75N93019C00052. TR is also supported in part as an Eminent Scholar by the Georgia Research Alliance, GRA-001.