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Vaccines and Antiviral Agents

Adenovirus-Based Vaccines: Comparison of Vectors from Three Species of Adenoviridae

H. Chen, Z. Q. Xiang, Y. Li, R. K. Kurupati, B. Jia, A. Bian, D. M. Zhou, N. Hutnick, S. Yuan, C. Gray, J. Serwanga, B. Auma, P. Kaleebu, X. Zhou, M. R. Betts, H. C. J. Ertl
H. Chen
1The Wistar Institute, Philadelphia, Pennsylvania
5Department of Immunology, Tong Ji University, Shanghai, China
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Z. Q. Xiang
1The Wistar Institute, Philadelphia, Pennsylvania
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Y. Li
1The Wistar Institute, Philadelphia, Pennsylvania
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R. K. Kurupati
1The Wistar Institute, Philadelphia, Pennsylvania
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B. Jia
1The Wistar Institute, Philadelphia, Pennsylvania
6Department of Infectious Diseases, First Affiliated Hospital of Chongqing Medical University, Chongqing, China
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A. Bian
1The Wistar Institute, Philadelphia, Pennsylvania
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D. M. Zhou
1The Wistar Institute, Philadelphia, Pennsylvania
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N. Hutnick
2Department of Microbiology, University of Pennsylvania, Philadelphia, Pennsylvania
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S. Yuan
2Department of Microbiology, University of Pennsylvania, Philadelphia, Pennsylvania
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C. Gray
2Department of Microbiology, University of Pennsylvania, Philadelphia, Pennsylvania
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J. Serwanga
3AIDS Research Unit, National Institute for Communicable Diseases, Johannesburg, South Africa
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B. Auma
4MRC/UVRI Uganda Research Unit on AIDS, Entebbe, Uganda
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P. Kaleebu
4MRC/UVRI Uganda Research Unit on AIDS, Entebbe, Uganda
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X. Zhou
1The Wistar Institute, Philadelphia, Pennsylvania
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M. R. Betts
2Department of Microbiology, University of Pennsylvania, Philadelphia, Pennsylvania
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H. C. J. Ertl
1The Wistar Institute, Philadelphia, Pennsylvania
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  • For correspondence: ertl@wistar.upenn.edu
DOI: 10.1128/JVI.00450-10
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ABSTRACT

In order to better understand the broad applicability of adenovirus (Ad) as a vector for human vaccine studies, we compared four adenovirus (Ad) vectors from families C (Ad human serotype 5 [HAdV-5; here referred to as AdHu5]), D (HAdV-26; here referred to as AdHu26), and E (simian serotypes SAdV-23 and SAdV-24; here referred to as chimpanzee serotypes 6 and 7 [AdC6 and AdC7, respectively]) of the Adenoviridae. Seroprevalence rates and titers of neutralizing antibodies to the two human-origin Ads were found to be higher than those reported previously, especially in countries of sub-Saharan Africa. Conversely, prevalence rates and titers to AdC6 and AdC7 were markedly lower. Healthy human adults from the United States had readily detectable circulating T cells recognizing Ad viruses, the levels of which in some individuals were unexpectedly high in response to AdHu26. The magnitude of T-cell responses to AdHu5 correlated with those to AdHu26, suggesting T-cell recognition of conserved epitopes. In mice, all of the different Ad vectors induced CD8+ T-cell responses that were comparable in their magnitudes and cytokine production profiles. Prime-boost regimens comparing different combinations of Ad vectors failed to indicate that the sequential use of Ad vectors from distinct families resulted in higher immune responses than the use of serologically distinct Ad vectors from the same family. Moreover, the transgene product-specific antibody responses induced by the AdHu26 and AdC vectors were markedly lower than those induced by the AdHu5 vector. AdHu26 vectors and, to a lesser extent, AdC vectors induced more potent Ad-neutralizing antibody responses. These results suggest that the potential of AdHu26 as a vaccine vector may suffer from limitations similar to those found for vectors based on other prevalent human Ads.

  • Copyright © 2010 American Society for Microbiology
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Adenovirus-Based Vaccines: Comparison of Vectors from Three Species of Adenoviridae
H. Chen, Z. Q. Xiang, Y. Li, R. K. Kurupati, B. Jia, A. Bian, D. M. Zhou, N. Hutnick, S. Yuan, C. Gray, J. Serwanga, B. Auma, P. Kaleebu, X. Zhou, M. R. Betts, H. C. J. Ertl
Journal of Virology Sep 2010, 84 (20) 10522-10532; DOI: 10.1128/JVI.00450-10

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Adenovirus-Based Vaccines: Comparison of Vectors from Three Species of Adenoviridae
H. Chen, Z. Q. Xiang, Y. Li, R. K. Kurupati, B. Jia, A. Bian, D. M. Zhou, N. Hutnick, S. Yuan, C. Gray, J. Serwanga, B. Auma, P. Kaleebu, X. Zhou, M. R. Betts, H. C. J. Ertl
Journal of Virology Sep 2010, 84 (20) 10522-10532; DOI: 10.1128/JVI.00450-10
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KEYWORDS

Adenoviridae
Genetic Vectors
Viral Vaccines

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