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Journal of Virology, February 2005, p. 1701-1712, Vol. 79, No. 3
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.3.1701-1712.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Contribution of Virus-Like Particles to the Immunogenicity of Human Immunodeficiency Virus Type 1 Gag-Derived Vaccines in Mice

S. B. Justin Wong1 and Robert F. Siliciano1,2*

Program in Cellular and Molecular Medicine,1 Graduate Program in Immunology, Department of Medicine and Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland2

Received 2 July 2004/ Accepted 21 September 2004

The human immunodeficiency virus type 1 (HIV-1) Gag protein is a major target antigen for cytotoxic-T-lymphocyte-based vaccine strategies because of its high level of conservation. The murine model has been used extensively to evaluate potential HIV-1 vaccines. However, the biology of HIV-1 Gag is somewhat different in human and murine tissues. The ability of HIV-1 Gag to form virus-like particles (VLPs) in human cells is severely curtailed in murine cells. Hence, it is not known whether immunizing mice with expression vectors encoding HIV-1 Gag provides an accurate assessment of the immunogenicity of these candidate vaccines in primates. In this report, we made use of a chimeric Moloney murine leukemia virus (MMLV)-HIV-1 Gag in which the p17 matrix domain of HIV-1 was replaced with the p15 matrix and p12 domains from MMLV. Murine cells expressing this construct released significant amounts of VLPs. The construct preserved H-2d-restricted antigenic determinants in the remaining portion of HIV-1 Gag, allowing immunogenicity studies to be performed with mice. We demonstrated that immunizing mice with plasmid DNA or adenoviral vectors encoding this chimeric Gag did not significantly increase the HIV-1 Gag-specific cellular or humoral immune response when compared to immunization with a myristoylation-incompetent version of the construct. Thus, the release of VLPs formed in vivo may not play a major role in the immunogenicity of vectors expressing HIV-1 Gag constructs.

* Corresponding author. Mailing address: Department of Medicine, Johns Hopkins University School of Medicine, Broadway Research Building Suite 879, 733 North Broadway, Baltimore, MD 21205. Phone: (410) 955-2958. Fax: (410) 955-0964. E-mail: rsilicia{at}jhmi.edu.

Journal of Virology, February 2005, p. 1701-1712, Vol. 79, No. 3
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.3.1701-1712.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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