Cytokine responses to human immunodeficiency virus type 1 (HIV-1) induced by immunization with live recombinant canarypox virus vaccine expressing HIV-1 genes boosted by HIV-1(SF-2) recombinant GP120.

Vaccine-induced T-cell memory for human immunodeficiency virus type 1 (HIV-1) was assessed by measuring HIV-1 antigen-stimulated cytokine secretion in 72 HIV-1-uninfected subjects, of whom 52 received live recombinant canarypox virus vaccine expressing HIV-1 env, gag, and protease gene products (vCP205) with or without HIV-1(SF-2) recombinant gp120 (SF-2 rgp120) subunit vaccine, and 20 the control. The vCP205 vaccine induced secretion of the Th1 cytokine, interferon-gamma, by peripheral blood mononuclear cells (PBMC) after in vitro stimulation with HIV-1 p24 and envelope glycoprotein. Immunization schedules with both vCP205 and SF-2 rgp120 subunit vaccines induced secretion of Th1 and Th2 cytokines by PBMC to HIV-1 envelope glycoprotein. Hence, vCP205 and SF-2 rgp120 subunit vaccines given together and in a prime-boost sequence appeared to induce a broader cytokine response pattern than vCP205 vaccine given alone.

Vaccine-induced cytotoxic T lymphocytes against human immunodeficiency virus type 1 using two complementary in vitro stimulation strategies.

CD8+ cytotoxic T lymphocytes (CTL) against human immunodeficiency virus type 1 (HIV-1) induced by candidate HIV-1 vaccines may be a mechanism of immune protection against HIV-1 infection. We measured in vitro inducible CD8+ and CD4+ CTL using two in vitro effector cell stimulation strategies. Peripheral blood mononuclear cells (PBMC) for CTL assay were obtained after the third and/or fourth immunization timepoints from 23 healthy, uninfected adult volunteers, of whom 19 received a canarypox virus vaccine expressing HIV-1 env, gag, pol, nef and protease gene products (vCP300) with or without injections of HIV-1(SF-2) rgp120 subunit vaccine and four subjects received only control injections. CD8+ CTL activity was detected employing the two in vitro stimulation strategies against one or more HIV-1 antigens in 15 (79%) of 19 HIV-1 vaccine recipients on at least one occasion and repeatedly against the same antigen in 8 (42%). Canarypox virus-based HIV-1 vaccines represent a step forward in HIV-1 vaccine development.

MN and IIIB recombinant glycoprotein 120 vaccine-induced binding antibodies to native envelope glycoprotein of human immunodeficiency virus type 1 primary isolates. National Institute of Allergy and Infectious Disease Aids Vaccine Evaluation Group.

The ability of antibody induced by MN and IIIB recombinant gp120 (rgp120) human immunodeficiency virus type 1 (HIV-1) vaccines to bind to oligomeric native HIV-1 envelope glycoproteins of primary isolates of HIV-1 was measured by flow cytometric indirect immunofluorescence assay (FIFA) in 25 uninfected, healthy adults. After three immunizations, MN rgp120 HIV-1 vaccine given alone and coadministered with IIIB rgp120 HIV-1 vaccine elicited antibody that bound to cells infected with each of a panel of six subtype B strains of HIV-1. Lower levels of vaccine-induced binding antibody were detected against envelope subtype A, D, and (EA) strains of HIV-1 than against subtype B strains. Priming immunization with IIIB rgp120 HIV-1 vaccine alone induced low levels of antibody capable of binding to envelope glycoprotein of primary isolate strains of HIV-1, and booster immunizations with MN rgp120 HIV-1 vaccine resulted in much higher antibody levels. We conclude that MN rgp120 HIV-1 vaccine was an effective inducer of antibody to native envelope glycoproteins of antigenically diverse primary isolates of HIV-1.

HIV-1MN recombinant glycoprotein 160 vaccine-induced cellular and humoral immunity boosted by HIV-1MN recombinant glycoprotein 120 vaccine. National Institute of Allergy and Infectious Diseases AIDS Vaccine Evaluation Group.

We evaluated prime-boost immunization with two recombinant envelope glycoprotein subunit vaccines (HIV-1MN recombinant gp160 vaccine in alum adjuvant [MN rgp160] and HIV-1MN recombinant gp120 vaccine in alum adjuvant [MN rgp120]) for safety and immunogenicity in healthy, HIV-1-uninfected adults. The rationale was to combine the helper T cell memory and binding antibody responses typically induced by rgp160 vaccines with the superior neutralizing antibody responses induced by rgp120 vaccines. In a double-blinded, controlled trial, volunteers were randomly assigned to receive MN rgp160 or adjuvant placebo, and a subset later received MN rgp120. The two vaccines were safe, but reactions to MN rgp160 and its adjuvant placebo exceeded those to MN rgp120. MN rgp160 induced IgG binding antibodies, including all IgG subclasses, to MN rgp160 in all vaccine recipients. HIV-1MN-neutralizing and anti-V3 MN peptide-binding antibodies were observed in a majority of volunteers after the fourth MN rgp160 immunization, but at lower levels compared with immunization with MN rgp120 in historical controls. HIV-1-binding, neutralizing, and fusion inhibition antibodies were boosted to the highest levels among MN rgp160 recipients after MN rgp120 booster injections. MN rgp120 boosting appeared to alter the distribution of MN rgp160 vaccine-induced, anti-MN rgp160 IgG subclass antibodies. MN rgp160 induced helper T cell memory, measured by lymphocyte proliferation, Thl and Th2 cytokine production, and skin testing. Strategies including both subunit vaccines may help maximize antibody and helper T cell memory responses to HIV-1 envelope glycoprotein.

Recombinant gp160 vaccination schedule and MHC HLA type as factors influencing cellular responses to HIV-1 envelope glycoprotein. NIAID AIDS Vaccine Clinical Trials Network.

This study assessed (1) T-cell responses following vaccination of HIV-1 negative volunteers with HIV-1LAI recombinant gp160 (rgp160) vaccine, and (2) effects of vaccine injection schedule and MHC HLA type on those responses. In one trial, volunteers received rgp160 in two accelerated schedules (Groups 1 and 2). In the other trial, volunteers received rgp160 vaccine at 0, 1, 6, and 12 months and some received vaccine at 18 months (Groups 3 and 4). Peripheral blood mononuclear cells (PBMC) from vaccinees in Groups 3 and 4 were stimulated by more peptides representing envelope glycoprotein T-cell epitopes than Groups 1 and 2 (p = 0.01). Transient anti-envelope glycoprotein CTL activity was more frequently detectable in Groups 1 and 2 (p = 0.03). MHC HLA-Cw7, DR1 and DQw1 alleles appeared to be associated with PBMC responses to envelope glycoprotein.