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Journal of Virology, October 2004, p. 10249-10257, Vol. 78, No. 19
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.19.10249-10257.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Human Immunodeficiency Virus Type 1 Gag-Specific Mucosal Immunity after Oral Immunization with Papillomavirus Pseudoviruses Encoding Gag

Hongtao Zhang, Raja Fayad, Xilin Wang, Daniel Quinn, and Liang Qiao*

Department of Microbiology and Immunology, Stritch School of Medicine, Loyola University Chicago Medical Center, Maywood, Illinois

Received 6 January 2004/ Accepted 27 May 2004

Mucosal surfaces are the primary portals for human immunodeficiency virus (HIV) transmission. Because systemic immunization, in general, does not induce effective mucosal immune responses, a mucosal HIV vaccine is urgently needed. For this study, we developed papillomavirus pseudoviruses that express HIV-1 Gag. The pseudoviruses are synthetic, nonreplicating viruses, yet they can produce antigens for a long time in the immune system. Here we show that oral immunization of mice by the use of papillomavirus pseudoviruses encoding Gag generated mucosal and systemic Gag-specific cytotoxic T lymphocytes that effectively lysed Gag-expressing target cells. Furthermore, the pseudoviruses generated Gag-specific gamma interferon-producing T cells and serum immunoglobulin G (IgG) and mucosal IgA. In contrast, oral immunization with plasmid DNA encoding HIV-1 Gag did not induce specific immune responses. Importantly, oral immunization with the pseudoviruses induced Gag-specific memory cytotoxic T lymphocytes and protected mice against a rectal mucosal challenge with a recombinant vaccinia virus expressing HIV-1 Gag. Thus, papillomavirus pseudoviruses encoding Gag are a promising mucosal vaccine against AIDS.


* Corresponding author. Mailing address: Department of Microbiology and Immunology, Stritch School of Medicine, Loyola University Chicago Medical Center, 2160 South First Ave., Maywood, IL 60153. Phone: (708) 327-3481. Fax: (708) 216-1196. E-mail: lqiao{at}lumc.edu.


Journal of Virology, October 2004, p. 10249-10257, Vol. 78, No. 19
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.19.10249-10257.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.




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