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Journal of Virology, April 2002, p. 3309-3317, Vol. 76, No. 7
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.7.3309-3317.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Induction of Mucosal Protection against Primary, Heterologous Simian Immunodeficiency Virus by a DNA Vaccine

Deborah Heydenburg Fuller,1 Premeela A. Rajakumar,2 Lawrence A. Wilson,3 Anita M. Trichel,2 James T. Fuller,1 Tim Shipley,1 Mary S. Wu,1 Kathleen Weis,1 Charles R. Rinaldo,2 Joel R. Haynes,1 and Michael Murphey-Corb2*

PowderJect Vaccines, Inc., Madison, Wisconsin 53711,1 University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261,2 Tulane Regional Primate Research Center, Covington, Louisiana 704333

Received 7 August 2001/ Accepted 27 September 2001

An effective vaccine against human immunodeficiency virus (HIV) should protect against mucosal transmission of genetically divergent isolates. As a safe alternative to live attenuated vaccines, the immunogenicity and protective efficacy of a DNA vaccine containing simian immunodeficiency virus (SIV) strain 17E-Fr (SIV/17E-Fr) gag-pol-env was analyzed in rhesus macaques. Significant levels of cytotoxic T lymphocytes (CTL), but low to undetectable serum antibody responses, were observed following multiple immunizations. SIV-specific mucosal antibodies and CTL were also detected in rectal washes and gut-associated lymphoid tissues, respectively. Vaccinated and naive control monkeys were challenged intrarectally with SIV strain DeltaB670 (SIV/DeltaB670), a primary isolate whose env is 15% dissimilar to that of the vaccine strain. Four of seven vaccinees were protected from infection as determined by the inability to identify viral RNA or DNA sequences in the peripheral blood and the absence of anamnestic antibody responses postchallenge. This is the first report of mucosal protection against a primary pathogenic, heterologous isolate of SIV by using a commercially viable vaccine approach. These results support further development of a DNA vaccine for protection against HIV.


* Corresponding author. Mailing address: University of Pittsburgh School of Medicine, Department of Molecular Genetics and Biochemistry, Room E1240 Biomedical Science Tower, Pittsburgh, PA 15261. Phone: (412) 648-9462. Fax: (412) 648-1448. E-mail: mcorb{at}pitt.edu.


Journal of Virology, April 2002, p. 3309-3317, Vol. 76, No. 7
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.7.3309-3317.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.




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