Abstract
The emergence of multiple novel lineages of H1 and H3 influenza A viruses in swine has confounded control by inactivated vaccines. Because of substantial genetic and geographic heterogeneity among circulating swine influenza viruses, one vaccine strain per subtype cannot be efficacious against all of the current lineages. We have performed vaccination-challenge studies in pigs to examine whether priming and booster vaccinations with antigenically distinct H3N2 swine influenza viruses could broaden antibody responses and protection. We prepared monovalent whole inactivated, adjuvanted vaccines based on a European and a North American H3N2 swine influenza virus, which showed 81.5% aa homology in the HA1 region of the hemagglutinin and 83.4% in the neuraminidase. Our data show that (i) Priming with European and boosting with North American H3N2 swine influenza virus induces antibodies and protection against both vaccine strains, unlike prime-boost vaccination with a single virus or a single administration of bivalent vaccine. (ii) The heterologous prime-boost vaccination enhances hemagglutination inhibiting, virus neutralizing and neuraminidase inhibiting antibody responses against H3N2 viruses that are antigenically distinct from both vaccine strains. Antibody titers to the most divergent viruses were higher than after two administrations of bivalent vaccine. (iii) However, it does not induce antibodies to the conserved hemagglutinin stalk or to other hemagglutinin subtypes. We conclude that heterologous prime-boost vaccination might broaden protection to H3N2 swine influenza viruses and reduce the total amount of vaccine needed. This strategy holds potential for vaccination against influenza viruses from both humans and swine and for a better control of (reverse) zoonotic transmission of influenza viruses.
Highlights
Inactivated influenza vaccines protect by inducing serum antibody against the hemagglutinin (HA) and, to a lesser degree, the neuraminidase (NA) of the vaccine strains
We first examined the evolution of antibody titers against both vaccine strains by hemagglutination inhibition (HI), virus neutralization (VN) and neuraminidase inhibition (NI)
Anti-G08 titers were significantly higher in the heterologous prime-boost group than in the bivalent vaccine (1x) group, but there were no significant differences in anti-PA10 titers, except for HI titers at week 8
Summary
Inactivated influenza vaccines protect by inducing serum antibody against the hemagglutinin (HA) and, to a lesser degree, the neuraminidase (NA) of the vaccine strains. While the HA is highly immunogenic and the target for neutralizing antibodies, it is the most variable protein. For this reason, human influenza vaccine strains are updated every few years.[1] Influenza A viruses of H1N1, H3N2, and H1N2 subtypes are enzootic in swine worldwide[2] and both the viruses and the inactivated vaccines for swine resemble those of humans. There is no formal system to recommend vaccine strains for swine and SIV vaccine strains are only rarely updated.[3] This is in part due to slower antigenic drift of influenza viruses in swine than in humans[4, 5] and to regulatory and economic constraints. The prevailing lineages differ between continents and regions, and SIV vaccines for Europe and North
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