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Sci Rep. 2017 Nov 27;7(1):16379. doi: 10.1038/s41598-017-16419-w.
Virus replicon particle vaccines expressing nucleoprotein of influenza A virus mediate enhanced inflammatory responses in pigs.
Ricklin ME1, Python S1, Vielle NJ1, Brechb?hl D1, Zumkehr B1, Posthaus H2,3, Zimmer G1, Ruggli N1, Summerfield A4,5.
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Abstract
Studies in the mouse model indicate that the nucleoprotein of influenza A virus represents an interesting vaccine antigen being well conserved across subtypes of influenza virus but still able to induce protective immune responses. Here we show that immunizations of pigs with vesicular stomatitis virus- and classical swine fever virus-derived replicon (VRP) particles expressing the nucleoprotein (NP) of H1N1 A/swine/Belzig/2/01 induced potent antibody and T-cell responses against influenza A virus. In contrast to a conventional whole inactivated virus vaccine, the VRP vaccines induced both NP-specific CD4 and CD8 T cells responses, including interferon-γ and tumor-necrosis-factor dual-secreting cell. Although T-cells and antibody responses were cross-reactive with the heterologous H1N2 A/swine/Bakum/R757/2010 challenge virus, they did not provide protection against infection. Surprisingly, vaccinated pigs showed enhanced virus shedding, lung inflammation and increased levels of systemic and lung interferon-α as well as elevated lung interleukin-6. In conclusion, our study shows that NP, although efficacious in the mouse model, appears not to be a promising stand-alone vaccine antigen for pigs.
PMID: 29180817 DOI: 10.1038/s41598-017-16419-w
Free PMC Article
Virus replicon particle vaccines expressing nucleoprotein of influenza A virus mediate enhanced inflammatory responses in pigs.
Ricklin ME1, Python S1, Vielle NJ1, Brechb?hl D1, Zumkehr B1, Posthaus H2,3, Zimmer G1, Ruggli N1, Summerfield A4,5.
Author information
Abstract
Studies in the mouse model indicate that the nucleoprotein of influenza A virus represents an interesting vaccine antigen being well conserved across subtypes of influenza virus but still able to induce protective immune responses. Here we show that immunizations of pigs with vesicular stomatitis virus- and classical swine fever virus-derived replicon (VRP) particles expressing the nucleoprotein (NP) of H1N1 A/swine/Belzig/2/01 induced potent antibody and T-cell responses against influenza A virus. In contrast to a conventional whole inactivated virus vaccine, the VRP vaccines induced both NP-specific CD4 and CD8 T cells responses, including interferon-γ and tumor-necrosis-factor dual-secreting cell. Although T-cells and antibody responses were cross-reactive with the heterologous H1N2 A/swine/Bakum/R757/2010 challenge virus, they did not provide protection against infection. Surprisingly, vaccinated pigs showed enhanced virus shedding, lung inflammation and increased levels of systemic and lung interferon-α as well as elevated lung interleukin-6. In conclusion, our study shows that NP, although efficacious in the mouse model, appears not to be a promising stand-alone vaccine antigen for pigs.
PMID: 29180817 DOI: 10.1038/s41598-017-16419-w
Free PMC Article