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

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.