Studies on in vitro expression and in vivo immunogenicity of a recombinant MVA HIV vaccine.
Here we conduct dose-response studies for in vitro expression and in vivo immunogenicity for a recombinant modified vaccinia Ankara (MVA) vaccine that expresses HIV Gag, Pol, and Env proteins. The dose-response studies for in vitro expression used fluorescent-activated cell sorting to score Gag- and Env-expressing cells and showed good increases for antigen expression with increasing MVA dose. In these studies, a 1000-fold increase in the dose of MVA resulted in a 300-fold increase in the frequency of antigen-expressing cells. In contrast, dose-response studies for in vivo immunogenicity showed <10-fold increases in elicited T cells and Ab for 100-1000-fold increases in the dose of inoculated MVA. These studies used intracellular cytokine assays to enumerate responding CD8 and CD4 T cells and an ELISA to score anti-Env Ab. The shallow dose-response curves for immunogenicity were observed post priming as well as post boosting of an MVA or a DNA prime.
Emory Vaccine Center, Emory University School of Medicine and Yerkes National Primate Research Center, 954 Gatewood Road, Box 129, Atlanta, GA, USA.
Jinyan
J
Liu
Linda S
LS
Wyatt
Rama Rao
RR
Amara
Bernard
B
Moss
Harriet L
HL
Robinson
D016915:AIDS Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis; D004306:Dose-Response Relationship, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015870:Gene Expression; D015686:Gene Products, env / Q000235:genetics / Q000276:immunology; D015683:Gene Products, gag / Q000235:genetics / Q000276:immunology; D015684:Gene Products, pol / Q000235:genetics / Q000276:immunology; D015483:HIV Antibodies / Q000097:blood; D006801:Humans; D016131:Lymphocyte Subsets / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014616:Vaccinia virus / Q000235:genetics / Q000254:growth & development* / Q000276:immunology*; D014765:Viral Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
D016915:AIDS Vaccines; D016207:Cytokines; D015686:Gene Products, env; D015683:Gene Products, gag; D015684:Gene Products, pol; D015483:HIV Antibodies; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic; D014765:Viral Vaccines