Trivalent mRNA vaccine-candidate against seasonal flu with cross-specific humoral immune response

Front Immunol. 2024 Apr 16:15:1381508. doi: 10.3389/fimmu.2024.1381508. eCollection 2024.

Abstract

Seasonal influenza remains a serious global health problem, leading to high mortality rates among the elderly and individuals with comorbidities. Vaccination is generally accepted as the most effective strategy for influenza prevention. While current influenza vaccines are effective, they still have limitations, including narrow specificity for certain serological variants, which may result in a mismatch between vaccine antigens and circulating strains. Additionally, the rapid variability of the virus poses challenges in providing extended protection beyond a single season. Therefore, mRNA technology is particularly promising for influenza prevention, as it enables the rapid development of multivalent vaccines and allows for quick updates of their antigenic composition. mRNA vaccines have already proven successful in preventing COVID-19 by eliciting rapid cellular and humoral immune responses. In this study, we present the development of a trivalent mRNA vaccine candidate, evaluate its immunogenicity using the hemagglutination inhibition assay, ELISA, and assess its efficacy in animals. We demonstrate the higher immunogenicity of the mRNA vaccine candidate compared to the inactivated split influenza vaccine and its enhanced ability to generate a cross-specific humoral immune response. These findings highlight the potential mRNA technology in overcoming current limitations of influenza vaccines and hold promise for ensuring greater efficacy in preventing seasonal influenza outbreaks.

Keywords: efficacy; immune response; immunogenicity; mRNA; seasonal influenza; vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cross Reactions / immunology
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • HEK293 Cells
  • Hemagglutinin Glycoproteins, Influenza Virus / immunology
  • Humans
  • Immunity, Humoral* / immunology
  • Influenza A Virus, H1N1 Subtype* / immunology
  • Influenza Vaccines* / administration & dosage
  • Influenza Vaccines* / chemistry
  • Influenza Vaccines* / immunology
  • Influenza, Human / immunology
  • Influenza, Human / prevention & control
  • Influenza, Human / virology
  • Mice
  • Mice, Inbred BALB C
  • Orthomyxoviridae Infections* / immunology
  • Orthomyxoviridae Infections* / prevention & control
  • Orthomyxoviridae Infections* / virology
  • Seasons
  • Time Factors
  • mRNA Vaccines* / administration & dosage
  • mRNA Vaccines* / chemistry
  • mRNA Vaccines* / genetics
  • mRNA Vaccines* / immunology

Substances

  • Hemagglutinin Glycoproteins, Influenza Virus
  • Influenza Vaccines
  • mRNA Vaccines

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was funded by National Research Centre for Epidemiology and Microbiology named after Honorary Academician N F Gamaleya (from the income-generating activities) and the grant #121102500071-6 provided by the Ministry of Health of the Russian Federation, Russia.