tetano
Editor, Senior Moderator
Front Immunol. 2016 Jun 30;7:253. doi: 10.3389/fimmu.2016.00253. eCollection 2016.
[h=1]Partial Protection against Porcine Influenza A Virus by a Hemagglutinin-Expressing Virus Replicon Particle Vaccine in the Absence of Neutralizing Antibodies.[/h] Ricklin ME[SUP]1[/SUP], Vielle NJ[SUP]1[/SUP], Python S[SUP]1[/SUP], Brechb?hl D[SUP]1[/SUP], Zumkehr B[SUP]1[/SUP], Posthaus H[SUP]2[/SUP], Zimmer G[SUP]1[/SUP], Summerfield A[SUP]3[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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.
[h=4]KEYWORDS:[/h] CD4 T cells; VRP vaccine; hemagglutinin; influenza virus; neutralization; opsonization; pig
PMID: 27446083 PMCID: PMC4928594 DOI: 10.3389/fimmu.2016.00253
[PubMed] Free full text
[h=1]Partial Protection against Porcine Influenza A Virus by a Hemagglutinin-Expressing Virus Replicon Particle Vaccine in the Absence of Neutralizing Antibodies.[/h] Ricklin ME[SUP]1[/SUP], Vielle NJ[SUP]1[/SUP], Python S[SUP]1[/SUP], Brechb?hl D[SUP]1[/SUP], Zumkehr B[SUP]1[/SUP], Posthaus H[SUP]2[/SUP], Zimmer G[SUP]1[/SUP], Summerfield A[SUP]3[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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.
[h=4]KEYWORDS:[/h] CD4 T cells; VRP vaccine; hemagglutinin; influenza virus; neutralization; opsonization; pig
PMID: 27446083 PMCID: PMC4928594 DOI: 10.3389/fimmu.2016.00253
[PubMed] Free full text