A Herpes Simplex Virus Type-1-Derived Influenza Vaccine Induces Balanced Adaptive Immune Responses and Protects Mice From Lethal Influenza Virus Challenge

J Med Virol. 2024 Nov;96(11):e70067. doi: 10.1002/jmv.70067.

Abstract

Influenza virus is a major respiratory viral pathogen responsible for the deaths of hundreds of thousands worldwide each year. Current vaccines provide protection primarily by inducing strain-specific antibody responses with the requirement of a match between vaccine strains and circulating strains. It has been suggested that anti-influenza T-cell responses, in addition to antibody responses may provide the broadest protection against different flu strains. Therefore, to address this urgent need, it is desirable to develop a vaccine candidate with an ability to induce balanced adaptive immunity including cell mediated immune responses. Here, we explored the potential of VC2, a well-characterized Herpes Simplex Virus type 1 vaccine vector, as a live attenuated influenza vaccine candidate. We generated a recombinant VC2 virus expressing the influenza A hemagglutinin protein. We show that this virus is capable of generating potent and specific anti-influenza humoral and cell-mediated immune responses. We further show that a single vaccination with the VC2-derived influenza vaccine protects mice from lethal challenge with influenza virus. Our data support the continued development of VC2-derived influenza vaccines for protection of human populations from both seasonal and pandemic strains of influenza. Finally, our results support the potential of VC2-derived vaccines as a platform for the rapid development of vaccines against emerging and established pathogens, particularly respiratory pathogens.

Keywords: cell‐mediated immunity; disease control; immune responses; influenza virus; vaccines/vaccine strains; virus classification.

MeSH terms

  • Adaptive Immunity*
  • Animals
  • Antibodies, Viral* / blood
  • Antibodies, Viral* / immunology
  • Disease Models, Animal
  • Female
  • Genetic Vectors / immunology
  • Hemagglutinin Glycoproteins, Influenza Virus / genetics
  • Hemagglutinin Glycoproteins, Influenza Virus / immunology
  • Herpesvirus 1, Human* / genetics
  • Herpesvirus 1, Human* / immunology
  • Humans
  • Immunity, Cellular
  • Influenza Vaccines* / administration & dosage
  • Influenza Vaccines* / immunology
  • Mice
  • Mice, Inbred BALB C*
  • Orthomyxoviridae Infections* / immunology
  • Orthomyxoviridae Infections* / prevention & control
  • Survival Analysis
  • Vaccines, Attenuated* / administration & dosage
  • Vaccines, Attenuated* / immunology
  • Vaccines, Synthetic / administration & dosage
  • Vaccines, Synthetic / genetics
  • Vaccines, Synthetic / immunology

Substances

  • Influenza Vaccines
  • Antibodies, Viral
  • Vaccines, Attenuated
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Vaccines, Synthetic