Immune response to HIV-1 gag antigens induced by recombinant adenovirus vectors in mice and rhesus macaque monkeys.
Recombinant adenovirus vectors expressing the entire gag (p55) or CA (p24) region of human immunodeficiency virus type 1 (HIV-1) were constructed by inserting the appropriate HIV DNA sequences into the E3 region of human adenovirus type 5 (Ad5) with and without an exogenous SV40 early promoter. The infectious recombinant adenoviruses Adgag1, AdSVgag1, and AdSVCA1 were shown to express the appropriate HIV-1 antigens in human cells in vitro, as measured by immunoprecipitation and p24 antigen capture assays. Using the p24 antigen capture assay, HIV antigen expressed by AdSVCA1 was detected earlier in infection and in greater amounts than that produced by either Adgag1 or AdSVgag1. In studies concerning the immunogenicity of these vectors, Balb/c (H-2d) mice given a single intraperitoneal injection of 10(7) or 10(8) plaque-forming units of purified vector developed serum antibodies to p24, detected by Western blotting, by 2 weeks postinjection. In the preliminary test of the immunogenicity of the recombinant adenovirus vectors in primates, two of four rhesus macaque monkeys generated antibodies to HIV-1 p24 following two injections of AdSVCA1. As expected, monkeys injected with control adenovirus failed to show any anti-HIV response, and none of the monkeys showed any adverse reactions following infection with either recombinant or control adenoviruses. These results suggest that adenovirus vectors have considerable potential in the study of possible immune therapies for HIV infection.
Prevec
L
L
Department of Pathology, McMaster University, Hamilton, Ontario, Canada.
Christie
B S
BS
Laurie
K E
KE
Bailey
M M
MM
Graham
F L
FL
Rosenthal
K L
KL
D000260:Adenoviruses, Human / Q000235:genetics* / Q000276:immunology; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D004274:DNA, Recombinant; D005260:Female; D015683:Gene Products, gag / Q000235:genetics / Q000276:immunology*; D005822:Genetic Vectors; D015483:HIV Antibodies / Q000096:biosynthesis*; D016655:HIV Core Protein p24; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D007114:Immunization; D007117:Immunization, Secondary; D008253:Macaca mulatta; D051379:Mice; D008807:Mice, Inbred BALB C; D011498:Protein Precursors / Q000235:genetics / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology; D014758:Viral Core Proteins / Q000235:genetics / Q000276:immunology*; D014765:Viral Vaccines / Q000276:immunology*
D000914:Antibodies, Viral; D004274:DNA, Recombinant; D015683:Gene Products, gag; D015483:HIV Antibodies; D016655:HIV Core Protein p24; D011498:Protein Precursors; D014614:Vaccines, Synthetic; D014758:Viral Core Proteins; D014765:Viral Vaccines; C059767:p55 gag precursor protein, Human immunodeficiency virus 1