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 journalArticle

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

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Adenoviridae
Immunity
Vaccines
SAIDS Vaccines
Serogroup
Cellular Immunity
HIV-1
T-Lymphocytes

ASJC Scopus subject areas

  • Immunology

Cite this

Barouch, D. H., Pau, M. G., Custers, J. H. H. V., Koudstaal, W., Kostense, S., Havenga, M. J. E., ... Goudsmit, J. (2004). Immunogenicity of Recombinant Adenovirus Serotype 35 Vaccine in the Presence of Pre-Existing Anti-Ad5 Immunity. Journal of Immunology, 172(10), 6290-6297.

Immunogenicity of Recombinant Adenovirus Serotype 35 Vaccine in the Presence of Pre-Existing Anti-Ad5 Immunity. / Barouch, Dan H.; Pau, Maria G.; Custers, Jerome H H V; Koudstaal, Wouter; Kostense, Stefan; Havenga, Menzo J E; Truitt, Diana M.; Sumida, Shawn M.; Kishko, Michael G.; Arthur, Janelle C.; Korioth-Schmitz, Birgit; Newberg, Michael H.; Gorgone, Darci A.; Lifton, Michelle A.; Panicali, Dennis L.; Nabel, Gary J.; Letvin, Norman L.; Goudsmit, Jaap.

In: Journal of Immunology, Vol. 172, No. 10, 15.05.2004, p. 6290-6297.

Research output: Contribution to journalArticle

Barouch, DH, Pau, MG, Custers, JHHV, Koudstaal, W, Kostense, S, Havenga, MJE, Truitt, DM, Sumida, SM, Kishko, MG, Arthur, JC, Korioth-Schmitz, B, Newberg, MH, Gorgone, DA, Lifton, MA, Panicali, DL, Nabel, GJ, Letvin, NL & Goudsmit, J 2004, 'Immunogenicity of Recombinant Adenovirus Serotype 35 Vaccine in the Presence of Pre-Existing Anti-Ad5 Immunity', Journal of Immunology, vol. 172, no. 10, pp. 6290-6297.
Barouch DH, Pau MG, Custers JHHV, Koudstaal W, Kostense S, Havenga MJE et al. Immunogenicity of Recombinant Adenovirus Serotype 35 Vaccine in the Presence of Pre-Existing Anti-Ad5 Immunity. Journal of Immunology. 2004 May 15;172(10):6290-6297.
Barouch, Dan H. ; Pau, Maria G. ; Custers, Jerome H H V ; Koudstaal, Wouter ; Kostense, Stefan ; Havenga, Menzo J E ; Truitt, Diana M. ; Sumida, Shawn M. ; Kishko, Michael G. ; Arthur, Janelle C. ; Korioth-Schmitz, Birgit ; Newberg, Michael H. ; Gorgone, Darci A. ; Lifton, Michelle A. ; Panicali, Dennis L. ; Nabel, Gary J. ; Letvin, Norman L. ; Goudsmit, Jaap. / Immunogenicity of Recombinant Adenovirus Serotype 35 Vaccine in the Presence of Pre-Existing Anti-Ad5 Immunity. In: Journal of Immunology. 2004 ; Vol. 172, No. 10. pp. 6290-6297.
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