Journal
JOURNAL OF VIROLOGY
Volume 78, Issue 6, Pages 2666-2673Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/JVI.78.6.2666-2673.2004
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Funding
- NIAID NIH HHS [P30 AI028691, K08 AI051223, P30 AI-28691, AI-51223] Funding Source: Medline
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The high prevalence of preexisting immunity to adenovirus serotype 5 (Ad5) in human populations will likely limit the inummogenicity and clinical utility of recombinant Ad5 vector-based vaccines for human immunodeficiency virus type 1 and other pathogens. Ad5-specific neutralizing antibodies (NAbs) are thought to contribute substantially to anti-Ad5 immunity, but the potential importance of Ad5-specific T lymphocytes in this setting has not been fully characterized. Here we assess the relative contributions of Ad5-specific Immoral and cellular immune responses in blunting the immunogenicity of a rAd5-Env vaccine in mice. Adoptive transfer of Ad5-specific NAbs resulted in a dramatic abrogation of Env-specific immune. responses following immunization with rAd5-Env. Interestingly, adoptive transfer of Ad5-specific CD8(+) T lymphocytes also resulted in a significant and durable suppression of rAd5-Env immunogenicity. These data demonstrate that NAbs and CD8(+) T lymphocytes both contribute to immunity to Ad5. Novel adenovirus vectors that are currently being developed to circumvent the problem of preexisting anti-Ad5 immunity should therefore be designed to evade both Immoral and cellular Ad5-specific immune responses.
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