Contribution of virus-like particles to the immunogenicity of human immunodeficiency virus type 1 Gag-derived vaccines in mice.
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.
Wong
S B Justin
SB
Program in Cellular and Moleculat Medicine, Department of Medicine and Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Broadway Research Building Suite 879, 733 North Broadway, Baltimore, MD 21205, USA.
Siliciano
Robert F
RF
D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D000256:Adenoviridae / Q000235:genetics / Q000276:immunology; D000818:Animals; D002460:Cell Line; D005260:Female; D015683:Gene Products, gag / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D005822:Genetic Vectors; D015483:HIV Antibodies / Q000097:blood; D015497:HIV-1 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007114:Immunization; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008979:Moloney murine leukemia virus / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*; D014771:Virion / Q000276:immunology* / Q000378:metabolism
D016915:AIDS Vaccines; D015683:Gene Products, gag; D015483:HIV Antibodies; D011993:Recombinant Fusion Proteins; D019444:Vaccines, DNA