Partial Protection against Porcine Influenza A Virus by a Hemagglutinin-Expressing Virus Replicon Particle Vaccine in the Absence of Neutralizing Antibodies.

Ricklin, Meret; Vielle, Nathalie Jane; Python, Sylvie; Brechbühl, Daniel; Zumkehr, Beatrice; Posthaus, Horst; Zimmer, Gert; Summerfield, Artur (2016). Partial Protection against Porcine Influenza A Virus by a Hemagglutinin-Expressing Virus Replicon Particle Vaccine in the Absence of Neutralizing Antibodies. Frontiers in immunology, 7(253), p. 253. Frontiers Research Foundation 10.3389/fimmu.2016.00253

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Virology and Immunology
05 Veterinary Medicine > Research Foci > Host-Pathogen Interaction
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Animal Pathology
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP)

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Ricklin, Meret; Vielle, Nathalie Jane; Posthaus, Horst; Zimmer, Gert and Summerfield, Artur

Subjects:

600 Technology > 630 Agriculture
500 Science > 570 Life sciences; biology

ISSN:

1664-3224

Publisher:

Frontiers Research Foundation

Language:

English

Submitter:

Achim Braun Parham

Date Deposited:

23 Mar 2017 13:50

Last Modified:

02 Apr 2017 02:21

Publisher DOI:

10.3389/fimmu.2016.00253

PubMed ID:

27446083

Uncontrolled Keywords:

CD4 T cells; VRP vaccine; hemagglutinin; influenza virus; neutralization; opsonization; pig

BORIS DOI:

10.7892/boris.96163

URI:

https://boris.unibe.ch/id/eprint/96163

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