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Clinical and Diagnostic Laboratory Immunology, March 2004, p. 351-357, Vol. 11, No. 2
1071-412X/04/$08.00+0     DOI: 10.1128/CDLI.11.2.351-357.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Prevalence of Neutralizing Antibodies to Adenoviral Serotypes 5 and 35 in the Adult Populations of The Gambia, South Africa, and the United States

Edward Nwanegbo,1 Eftyhia Vardas,2 Wentao Gao,1 Hilton Whittle,3 Huijie Sun,1 David Rowe,4 Paul D. Robbins,5 and Andrea Gambotto1,5,6*

Departments of Molecular Genetics and Biochemistry,5 Surgery,1 Infectious Disease, University of Pittsburgh School of Medicine,6 Departments of Infectious Disease and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania,4 HIV/AIDS Vaccine Division, Chris Hani Baragwanath Hospital, University of the Witwatersrand, Soweto, South Africa,2 Department of Virology, Medical Research Council, Banjul, The Gambia3

Received 7 October 2003/ Returned for modification 21 November 2003/ Accepted 4 December 2003

One of the major limitations of the use of adenoviruses as gene therapy vectors is the existence of preformed immunity in various populations. Recent studies have linked failure of adenoviral gene therapy trials to the presence of antiadenoviral neutralizing antibodies (NAb). Understanding the distribution and specificity of such antibodies will assist in the design of successful recombinant adenoviral gene therapies and vaccines. To assess the prevalence of NAb to adenovirus serotypes 5 and 35 (Ad5 and Ad35), we analyzed serum samples from adult immunocompetent individuals living in The Gambia, South Africa, and the United States by using a neutralization assay. Serum samples were incubated with A549 lung carcinoma cells and adenoviruses encoding enhanced green or yellow fluorescent proteins; results were analyzed by fluorescence microscopy and flow cytometry. Using this technique, we found a high prevalence of NAb against Ad5 in Gambian, South African, and U.S. subjects at both low and high titers. Conversely, all subjects displayed a low prevalence of NAb to Ad35; when present, anti-Ad35 NAb were seen at low titers. Because of the ability of adenoviruses to elicit systemic and mucosal immune responses, Ad35 with its low NAb prevalence appears to be an attractive candidate vector for gene therapy applications.

* Corresponding author. Mailing address: Department of Molecular Genetics and Biochemistry and Department of Surgery, University of Pittsburgh School of Medicine, Center for Biotechnology and Bioengineering, 300 Technology Dr., Suite 211, Pittsburgh, PA 15219. Phone: (412) 383-7684. Fax: (412) 383-9760. E-mail: agamb{at}imap.pitt.edu.

Clinical and Diagnostic Laboratory Immunology, March 2004, p. 351-357, Vol. 11, No. 2
1071-412X/04/$08.00+0     DOI: 10.1128/CDLI.11.2.351-357.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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