Immunogenicity of Recombinant Adenovirus Serotype 35 Vaccine in the Presence of Pre-Existing Anti-Ad5 Immunity

Dan H. Barouch, Maria G. Pau, Jerome H H V Custers, Wouter Koudstaal, Stefan Kostense, Menzo J E Havenga, Diana M. Truitt, Shawn M. Sumida, Michael G. Kishko, Janelle C. Arthur, Birgit Korioth-Schmitz, Michael H. Newberg, Darci A. Gorgone, Michelle A. Lifton, Dennis L. Panicali, Gary J. Nabel, Norman L. Letvin, Jaap Goudsmit

Research output: Contribution to journalArticlepeer-review

Abstract

The high prevalence of pre-existing immunity to adenovirus serotype 5 (Ad5) in human populations may substantially limit the immunogenicity and clinical utility of recombinant Ad5 vector-based vaccines for HIV-1 and other pathogens. A potential solution to this problem in to use vaccine vectors derived from adenovirus (Ad) serotypes that are rare in humans, such as Ad35. However, cross-reactive immune responses between heterologous Ad serotypes have been described and could prove a major limitation of this strategy. In particular, the extent of immunologic cross-reactivity between Ad5 and Ad35 has not previously been determined. In this study we investigate the impact of pre-existing anti-Ad5 immunity on the immunogenicity of candidate rAd5 and rAd35 vaccines expressing SIV Gag in mice. Anti-Ad5 immunity at levels typically found in humans dramatically blunted the immunogenicity of rAd5-Gag. In contrast, even high levels of anti-Ad5 immunity did not substantially suppress Gag-specific cellular immune responses elicited by rAd35-Gag. Low levels of cross-reactive Ad5/Ad35-specific CD4+ T lymphocyte responses were observed, but were insufficient to suppress vaccine immunogenicity. These data demonstrate the potential utility of Ad35 as a candidate vaccine vector that is minimally suppressed by anti-Ad5 immunity. Moreover, these studies suggest that using Ad vectors derived from immunologically distinct serotypes may be an effective and general strategy to overcome the suppressive effects of pre-existing anti-Ad immunity.

Original languageEnglish (US)
Pages (from-to)6290-6297
Number of pages8
JournalJournal of Immunology
Volume172
Issue number10
StatePublished - May 15 2004
Externally publishedYes

ASJC Scopus subject areas

  • Immunology

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