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Potent vesicular stomatitis virus-based avian influenza vaccines provide long-term sterilizing immunity against heterologous challenge.

ABSTRACT: The emergence in 1997 and continuance today of a highly lethal H5N1 avian influenza virus (AIV) causing human disease has raised concern about an impending pandemic and the need for a vaccine to prepare for such an occurrence. We previously generated an efficacious vesicular stomatitis virus (VSV)-based AIV vaccine expressing H5 hemagglutinin (HA) from the fifth genomic position of VSV (J. A. Schwartz et al., Virology 366:166-173, 2007). Here we have generated and characterized VSV-based vaccines that express the A/Hong Kong/156/1997 (clade 0) H5 HA from the first position of the VSV genome. These vectors induce broadly cross-neutralizing antibodies against homologous and heterologous H5N1 viruses of different clades in mice. The vaccines provide complete protection against morbidity and mortality after heterologous challenge with clade 0 and clade 1 strains in animals even 1 year after vaccination. Postchallenge pulmonary virus loads show that these vectors provide sterilizing immunity. Therefore, VSV-based AIV vaccines are potent, broadly cross-protective pandemic vaccine candidates.

SUBMITTER: Schwartz JA

PROVIDER: S-EPMC2863739 | biostudies-literature | 2010 May

REPOSITORIES: biostudies-literature

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Potent vesicular stomatitis virus-based avian influenza vaccines provide long-term sterilizing immunity against heterologous challenge.

Schwartz Jennifer A JA Buonocore Linda L Suguitan Amorsolo L AL Silaghi Alex A Kobasa Darwyn D Kobinger Gary G Feldmann Heinz H Subbarao Kanta K Rose John K JK

Journal of virology 20100224 9

The emergence in 1997 and continuance today of a highly lethal H5N1 avian influenza virus (AIV) causing human disease has raised concern about an impending pandemic and the need for a vaccine to prepare for such an occurrence. We previously generated an efficacious vesicular stomatitis virus (VSV)-based AIV vaccine expressing H5 hemagglutinin (HA) from the fifth genomic position of VSV (J. A. Schwartz et al., Virology 366:166-173, 2007). Here we have generated and characterized VSV-based vaccine ...[more]

PMID: 20181720

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Project description:BACKGROUND & AIMS:Infection with hepatitis B virus (HBV) can be prevented by vaccination with HB surface (HBs) antigen, which induces HBs-specific antibodies and T cells. However, the duration of vaccine-induced protective immunity is poorly defined for health care workers who were vaccinated as adults. METHODS:We investigated the immune mechanisms (antibody and T-cell responses) of long-term protection by the HBV vaccine in 90 health care workers with or without occupational exposure to HBV, 10-28 years after vaccination. RESULTS:Fifty-nine of 90 health care workers (65%) had levels of antibodies to HBs antigen above the cut-off (>12 mIU/mL) and 30 of 90 (33%) had HBs-specific T cells that produced interferon-gamma. Titers of antibodies to HBs antigen correlated with numbers of HBs-specific interferon-gamma-producing T cells, but not with time after vaccination. Although occupational exposure to HBV after vaccination did not induce antibodies to the HBV core protein (HBcore), the standard biomarker for HBV infection, CD4(+) and CD8(+) T cells against HBcore and polymerase antigens were detected. Similar numbers of HBcore- and polymerase-specific CD4(+) and CD8(+) T cells were detected in health care workers with occupational exposure to HBV and in patients who acquired immunity via HBV infection. Most of the HBcore- and polymerase-specific T cells were CD45RO(+)CCR7(-)CD127(-) effector memory cells in exposed health care workers and in patients with acquired immunity. In contrast, most of the vaccine-induced HBs-specific T cells were CD45RO(-)CCR7(-)CD127(-) terminally differentiated cells. CONCLUSIONS:HBs antigen vaccine-induced immunity protects against future infection but does not provide sterilizing immunity, as evidenced by HBcore- and polymerase-specific CD8(+) T cells in vaccinated health care workers with occupational exposure to HBV. The presence of HBcore- and HBV polymerase-specific T-cell responses is a more sensitive indicator of HBV exposure than detection of HBcore-specific antibodies.

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Potent vesicular stomatitis virus-based avian influenza vaccines provide long-term sterilizing immunity against heterologous challenge.

Publications

Potent vesicular stomatitis virus-based avian influenza vaccines provide long-term sterilizing immunity against heterologous challenge.

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