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Clinical and Vaccine Immunology, January 2006, p. 26-32, Vol. 13, No. 1
1071-412X/06/$08.00+0     doi:10.1128/CVI.13.1.26-32.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Cellular Immune Responses in Asymptomatic Human Immunodeficiency Virus Type 1 (HIV-1) Infection and Effects of Vaccination with Recombinant Envelope Glycoprotein of HIV-1

Geoffrey J. Gorse,1,2* Ramona E. Simionescu,2,{dagger} and Gira B. Patel2

Veterans Affairs Medical Center,1 Saint Louis University, St. Louis, Missouri2

Received 27 June 2005/ Returned for modification 31 August 2005/ Accepted 18 October 2005

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-{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 intracellularIFN-{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.

* Corresponding author. Mailing address: Division of Infectious Diseases and Immunology, Saint Louis University Health Sciences Center, School of Medicine, 3635 Vista Ave. (FDT-8N), St. Louis, MO 63110. Phone: (314) 577-8648. Fax: (314) 771-3816. E-mail: gorsegj{at}slu.edu.

{dagger} Present address: Infectious Diseases, P.C., 2325 Dougherty Ferry Road, #206, St. Louis, MO 63122.

Clinical and Vaccine Immunology, January 2006, p. 26-32, Vol. 13, No. 1
1071-412X/06/$08.00+0     doi:10.1128/CVI.13.1.26-32.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.





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