title: Partial Protection against Porcine Influenza A Virus by a Hemagglutinin-Expressing Virus Replicon Particle Vaccine in the Absence of Neutralizing Antibodies.
abstract: This work was initiated by previous reports demonstrating that mismatched influenza A virus (IAV) vaccines can induce enhanced disease, probably mediated by antibodies. Our aim was, therefore, to investigate if a vaccine inducing opsonizing but not neutralizing antibodies against the hemagglutinin (HA) of a selected heterologous challenge virus would enhance disease or induce protective immune responses in the pig model. To this end, we immunized pigs with either whole inactivated virus (WIV)-vaccine or HA-expressing virus replicon particles (VRP) vaccine based on recombinant vesicular stomatitis virus (VSV). Both types of vaccines induced virus neutralizing and opsonizing antibodies against homologous virus as shown by a highly sensitive plasmacytoid dendritic cell-based opsonization assay. Opsonizing antibodies showed a broader reactivity against heterologous IAV compared with neutralizing antibodies. Pigs immunized with HA-recombinant VRP vaccine were partially protected from infection with a mismatched IAV, which was not neutralized but opsonized by the immune sera. The VRP vaccine reduced lung lesions, lung inflammatory cytokine responses, serum IFN-α responses, and viral loads in the airways. Only the VRP vaccine was able to prime IAV-specific IFNγ/TNFα dual secreting CD4(+) T cells detectable in the peripheral blood. In summary, this work demonstrates that with the virus pair selected, a WIV vaccine inducing opsonizing antibodies against HA which lack neutralizing activity, is neither protective nor does it induce enhanced disease in pigs. In contrast, VRP-expressing HA is efficacious vaccines in swine as they induced both potent antibodies and T-cell immunity resulting in a broader protective value.
authors.affiliation: Institute of Virology and Immunology , Mittelhäusern , Switzerland.
authors.forename: Meret E
authors.initials: ME
authors.lastname: Ricklin
authors.affiliation: Institute of Virology and Immunology , Mittelhäusern , Switzerland.
authors.forename: Nathalie J
authors.initials: NJ
authors.lastname: Vielle
authors.affiliation: Institute of Virology and Immunology , Mittelhäusern , Switzerland.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Python
authors.affiliation: Institute of Virology and Immunology , Mittelhäusern , Switzerland.
authors.forename: Daniel
authors.initials: D
authors.lastname: Brechbühl
authors.affiliation: Institute of Virology and Immunology , Mittelhäusern , Switzerland.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Zumkehr
authors.affiliation: Vetsuisse Faculty, Institute for Animal Pathology, University of Bern , Bern , Switzerland.
authors.forename: Horst
authors.initials: H
authors.lastname: Posthaus
authors.affiliation: Institute of Virology and Immunology , Mittelhäusern , Switzerland.
authors.forename: Gert
authors.initials: G
authors.lastname: Zimmer
authors.affiliation: Institute of Virology and Immunology, Mittelhäusern, Switzerland; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
authors.forename: Artur
authors.initials: A
authors.lastname: Summerfield
keywords: CD4 T cells; VRP vaccine; hemagglutinin; influenza virus; neutralization; opsonization; pig