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Vaccines and Antiviral Agents

Vaccination with Adenovirus Serotypes 35, 26, and 48 Elicits Higher Levels of Innate Cytokine Responses than Adenovirus Serotype 5 in Rhesus Monkeys

Jeffrey E. Teigler, M. Justin Iampietro, Dan H. Barouch
Jeffrey E. Teigler
aDivision of Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
bRagon Institute of MGH, MIT, and Harvard, Boston, Massachusetts, USA
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M. Justin Iampietro
aDivision of Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
bRagon Institute of MGH, MIT, and Harvard, Boston, Massachusetts, USA
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Dan H. Barouch
aDivision of Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
bRagon Institute of MGH, MIT, and Harvard, Boston, Massachusetts, USA
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DOI: 10.1128/JVI.00740-12
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ABSTRACT

Adenovirus (Ad) vaccine vectors have proven highly immunogenic in multiple experimental models, but the innate immune responses induced by these vectors remain poorly characterized. Here we report innate cytokine responses to 5 different Ad vectors in 26 rhesus monkeys. Vaccination with adenovirus serotype 35 (Ad35), Ad26, and Ad48 induced substantially higher levels of antiviral (gamma interferon [IFN-γ], 10-kDa gamma interferon-induced protein [IP-10]) and proinflammatory (interleukin 1 receptor antagonist [IL-1RA], IL-6) cytokines than vaccination with Ad5 on day 1 following immunization. In vitro studies with capsid chimeric vectors and receptor-blocking monoclonal antibodies suggested that fiber-receptor interactions, as well as other capsid components, were critical for triggering these innate responses. Moreover, multiple cell populations, including dendritic cells, monocytes/macrophages, and T lymphocytes, contributed to these innate cytokine profiles. These data demonstrate that Ad35, Ad26, and Ad48, which utilize CD46 as their primary cellular receptor, induce significantly greater innate cytokine responses than Ad5, which uses the coxsackievirus and adenovirus receptor (CAR). These differences in innate triggering result in markedly different immunologic milieus for the subsequent generation of adaptive immune responses by these vaccine vectors.

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Vaccination with Adenovirus Serotypes 35, 26, and 48 Elicits Higher Levels of Innate Cytokine Responses than Adenovirus Serotype 5 in Rhesus Monkeys
Jeffrey E. Teigler, M. Justin Iampietro, Dan H. Barouch
Journal of Virology Aug 2012, 86 (18) 9590-9598; DOI: 10.1128/JVI.00740-12

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Vaccination with Adenovirus Serotypes 35, 26, and 48 Elicits Higher Levels of Innate Cytokine Responses than Adenovirus Serotype 5 in Rhesus Monkeys
Jeffrey E. Teigler, M. Justin Iampietro, Dan H. Barouch
Journal of Virology Aug 2012, 86 (18) 9590-9598; DOI: 10.1128/JVI.00740-12
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