Induction of HIV-specific functional immune responses by a multiclade HIV-1 DNA vaccine candidate in healthy Ugandans

• Published in: Vaccine 2007-11, Vol.25 (45), p.7737-7742
• Main Authors: Eller, Michael A, Eller, Leigh Anne, Opollo, Marc S, Ouma, Benson J, Oballah, Peter O, Galley, Lynee, Karnasuta, Chitraporn, Kim, Silvia Ratto, Robb, Merlin L, Michael, Nelson L, Kibuuka, Hannah, Wabwire-Mangen, Fred, Graham, Barney S, Birx, Deborah L, de Souza, Mark S, Cox, Josephine H
• Format: Article
• Language: English
• Subjects: Acquired immune deficiency syndrome; ADCC; Adenovirus; Adenoviruses, Human - genetics; AIDS; AIDS Vaccines - administration & dosage; AIDS Vaccines - immunology; Allergy and Immunology; Antibodies, Viral - blood; Biological and medical sciences; Chromium; CTL; Cytotoxicity; Cytotoxicity Tests, Immunologic; Cytotoxicity, Immunologic; Deoxyribonucleic acid; DNA; DNA vaccine; Double-Blind Method; Fundamental and applied biological sciences. Psychology; HIV; HIV Infections - immunology; HIV-1; HIV-1 - immunology; Human immunodeficiency virus; Human immunodeficiency virus 1; Humans; Immunization; Immunogenicity; LPA; Microbiology; Miscellaneous; Plasmids; Uganda; Vaccines; Vaccines, DNA - administration & dosage; Vaccines, DNA - immunology; Virology
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2007.08.056

Abstract A phase I randomized, double blind, placebo-controlled trial to assess the immunogenicity of a multiclade HIV-1 DNA plasmid vaccine was conducted in 31 HIV-1-negative Ugandans. Following immunization with DNA at 0, 1, and 2 months, the frequency of HIV-specific immune responses was assessed up to 10 months using a standard chromium release assay (CRA), lymphoproliferative assay (LPA), and antibody dependent cell-mediated cytotoxicity assay (ADCC). Seven of 15 (47%) vaccinees demonstrated CTL activity using the CRA to HIV-1 Env B with responses observed 1 month following the second vaccination and as late as 7 months following complete immunization. Additionally, lymphoproliferative reponses were observed in 14/15 vaccinees against p24. No CTL or LPA responses were observed at baseline or in the placebo group. ADCC activity was minimally induced by DNA vaccination. This study demonstrates that immunization with DNA alone induces CTL and lymphoproliferative responses in a population that will participate in a phase IIb study evaluating HIV-1 DNA priming followed by boosting with a replication-defective recombinant adenovirus vector.