Exploring Prime-Boost Vaccination Regimens with Different H1N1 Swine Influenza A Virus Strains and Vaccine Platforms

In a previous vaccination study in pigs, heterologous prime-boost vaccination with whole-inactivated H1N1 virus vaccines (WIV) induced superior antibody responses and protection compared to homologous prime-boost vaccination. However, no pan-H1 antibody response was induced. Therefore, to stimulate both local and systemic immune responses, we first vaccinated pigs intranasally with a pseudorabies vector vaccine expressing the pH1N1 hemagglutinin (prvCA09) followed by a homologous or heterologous WIV booster vaccine. Homologous and heterologous WIV–WIV vaccinated groups and mock-vaccinated or prvCA09 single-vaccinated pigs served as control groups. Five weeks after the second vaccination, pigs were challenged with a homologous pH1N1 or one of two heterologous H1N2 swine influenza A virus strains. A single prvCA09 vaccination resulted in complete protection against homologous challenge, and vector–WIV vaccinated groups were significantly better protected against heterologous challenge compared to the challenge control group or WIV–WIV vaccinated groups. Furthermore, vector–WIV vaccination resulted in broader hemagglutination inhibition antibody responses compared to WIV–WIV vaccination and higher numbers of antibody-secreting cells in peripheral blood, draining lymph nodes and nasal mucosa. However, even though vector–WIV vaccination induced stronger antibody responses and protection, we still failed to induce a pan-H1 antibody response.