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Journal of Virology, October 2003, p. 10850-10861, Vol. 77, No. 20
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.20.10850-10861.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Enhancement of gp120-Specific Immune Responses by Genetic Vaccination with the Human Immunodeficiency Virus Type 1 Envelope Gene Fused to the Gene Coding for Soluble CTLA4

Bishnu P. Nayak, Gangadhara Sailaja, and Abdul M. Jabbar^*

Department of Microbiology and Immunology, Emory Vaccine Center, Emory University School of Medicine, Emory University, Atlanta, Georgia 30329

Received 7 February 2003/ Accepted 18 July 2003

DNA vaccines exploit the inherent abilities of professional antigen-presenting cells to prime the immune system and to elicit immunity against diverse pathogens. In this study, we explored the possibility of augmenting human immunodeficiency virus type 1 gp120-specific immune responses by a DNA vaccine coding for a fusion protein, CTLA4:gp120, in mice. In vitro binding studies revealed that secreted CTLA4:gp120 protein induced a mean florescence intensity shift, when incubated with Raji B cells, indicating its binding to B7 proteins on Raji B cells. Importantly, we instituted three different vaccination regimens to test the efficacy of DNA vaccines encoding gp120 and CTLA4:gp120 in the induction of both cellular (CD8⁺) and antibody responses. Each of the vaccination regimens incorporated a single intramuscular (i.m.) injection of the DNA vaccines to prime the immune system, followed by two booster injections. The i.m.-i.m.-i.m. regimen induced only modest levels of gp120-specific CD8⁺ T cells, but the antibody response by CTLA4:gp120 DNA was nearly 16-fold higher than that induced by gp120 DNA. In contrast, using the i.m.-subcutaneous (s.c.)-i.m. regimen, it was found that gp120 and CTLA4:gp120 DNAs were capable of inducing significant levels of gp120-specific CD8⁺ T cells (3.5 and 11%), with antibody titers showing a modest twofold increase for CTLA4:gp120 DNA. In the i.m.-gene gun (g.g.)-g.g. regimen, the mice immunized with gp120 and CTLA4:gp120 harbored gp120-specific CD8⁺ T cells at frequencies of 0.9 and 2.9%, with the latter showing an eightfold increase in antibody titers. Thus, covalent antigen modification and the routes of genetic vaccination have the potential to modulate antigen-specific immune responses in mice.

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* Corresponding author. Mailing address: Department of Microbiology and Immunology, Emory University School of Medicine, Emory Vaccine Center, 954 Gatewood Rd., Atlanta, GA 30329. Phone: (404) 727-8001. Fax: (404) 727-8199. E-mail: jabbar{at}microbio.emory.edu. Present address: Department of Immunology, The Scripps Research Institute, La Jolla, CA 92137.

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Journal of Virology, October 2003, p. 10850-10861, Vol. 77, No. 20
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.20.10850-10861.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

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