Cellular immune responses in asymptomatic human immunodeficiency virus type 1 (HIV-1) infection and effects of vaccination with recombinant envelope glycoprotein of HIV-1.
Effects of human immunodeficiency virus type 1 (HIV-1) recombinant envelope glycoprotein vaccines on cell-mediated immune (CMI) responses were assessed in HIV-1-infected patients. Asymptomatic, antiretroviral-treatment-naïve, HIV-1-infected patients with CD4(+) T-cell counts greater than 400/microl received multiple intramuscular injections of HIV-1 IIIB recombinant envelope glycoprotein (rgp160) vaccine or HIV-1 MN recombinant envelope glycoprotein (rgp120) vaccine (eight patients, referred to as the HIV-1 vaccinees) or placebo or hepatitis B vaccine (three patients, referred to as the controls). Lymphocyte proliferation in response to HIV-1 envelope glycoproteins, both homologous and heterologous to the HIV-1 immunogens, was absent prior to study treatment in all patients but increased significantly during the vaccination series and after the final vaccination in HIV-1 vaccinees (P < 0.05) and remained absent in control patients. In flow cytometric analyses of intracellular cytokines, T-cell receptor stimulation with an anti-CD3 antibody induced gamma interferon (IFN-gamma) expression by activated CD4(+) and CD8(+) lymphocytes at greater frequencies than did stimulation with recombinant envelope glycoprotein and p24 of HIV-1 (P < 0.05). Mean frequencies of HIV-1 envelope glycoprotein-stimulated, activated intra-cellular IFN-gamma-producing CD4(+) and CD8(+) lymphocytes and of interleukin-2-producing CD4(+) lymphocytes did not increase after vaccination, but cytokine-producing cells were detectable in some patients. Comparing pre- to post-HIV-1 vaccination time points, changes in frequencies of activated, IFN-gamma-producing CD4(+) cells correlated inversely with changes in lymphocyte proliferation in response to recombinant envelope glycoprotein in HIV-1 vaccinees (P < 0.05). Increased CMI responses to HIV-1 envelope glycoprotein measured by lymphocyte proliferation were associated with HIV-1 recombinant envelope glycoprotein vaccines.
Gorse
Geoffrey J
GJ
Division of Infectious Diseases and Immunology, Saint Louis University Health Sciences Center, School of Medicine, 3635 Vista Ave. (FDT-8N), St. Louis, MO 63110, USA. gorsegj@slu.edu
Simionescu
Ramona E
RE
Patel
Gira B
GB
D016915:AIDS Vaccines / Q000627:therapeutic use*; D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D015699:HIV Envelope Protein gp120 / Q000627:therapeutic use*; D019302:HIV Envelope Protein gp160 / Q000627:therapeutic use*; D015658:HIV Infections / Q000276:immunology / Q000628:therapy*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D016233:Immunotherapy, Active / Q000379:methods; D007371:Interferon-gamma / Q000378:metabolism; D037181:Lectins, C-Type; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D014614:Vaccines, Synthetic / Q000627:therapeutic use*; D000099192:CD69 Antigens
D016915:AIDS Vaccines; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D015699:HIV Envelope Protein gp120; D019302:HIV Envelope Protein gp160; D007371:Interferon-gamma; D037181:Lectins, C-Type; D014614:Vaccines, Synthetic; D000099192:CD69 Antigens; C053473:VaxSyn HIV-1 (gp160) vaccine