ABSTRACT
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/μl
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-γ) 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 intracellularIFN-γ-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-γ-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.
Replacement of the V3 Domain in the Surface Subunit of the Feline Immunodeficiency Virus Envelope Glycoprotein with the Equivalent Region of a T Cell-Tropic Human Immunodeficiency Virus Type 1 Results in a Chimeric Surface Protein That Efficiently Binds to CXCR4