Journal Article

A Phase 1/2 Study of a Multiclade HIV-1 DNA Plasmid Prime and Recombinant Adenovirus Serotype 5 Boost Vaccine in HIV-Uninfected East Africans (RV 172)

Sawe, Fred, Dally, Len, Birx, Deborah L., Schunk, Mirjam S., Shaffer, Douglas, Michael, Nelson L., Eller, Michael A., Robb, Merlin L., de Souza, Mark S., Kibuuka, Hannah, Schindler, Karin B., Millard, Monica, Hoelscher, Michael, Maboko, Leonard, Graham, Barney, Bailer, Robert, Kibaya, Rukia, Schuetz, Alexandra, Cox, Josephine H., Eller, Leigh Anne, Kroll, Jason, Marovich, Mary, Kimutai, Robert, Kroidl, Arne

2010

Overview

Background. Human immunodeficiency virus (HIV) vaccine development remains a global priority. We describe the safety and immunogenicity of a multiclade DNA vaccine prime with a replication-defective recombinant adenovirus serotype 5 (rAd5) boost. Methods. The vaccine is a 6-plasmid mixture encoding HIV envelope (env) subtypes A, B, and C and subtype B gag, pol, and nef, and an rAd5 expressing identical genes, with the exception of nef. Three hundred and twentyfour participants were randomized to receive placebo (n = 138), a single dose of rAd5 at 1010 (n = 24) or 1011 particle units (n = 24), or DNA at 0, 1, and 2 months, followed by rAd5 at either 1010 (n = 114) or 1011 particle units (n = 24) boosting at 6 months. Participants were followed up for 24 weeks after the final vaccination. Results. The vaccine was safe and well tolerated. HIV-specific T cell responses were detected in 63% of vaccinees. Titers of preexisting Ad5 neutralizing antibody did not affect the frequency and magnitude of T cell responses in prime-boost recipients but did affect the response rates in participants that received rAd5 alone (P = .037). Conclusion. The DNA/rAd5 vaccination regimen was safe and induced HIV type 1 multi-clade T cell responses, which were not significantly affected by titers of preexisting rAd5 neutralizing antibody. Trial Registration. ClinicalTrials.gov identifier: NCT00123968.

• Publisher: The University of Chicago Press,University of Chicago Press,Oxford University Press
• Subject: Adenoviridae - genetics / Adenoviridae - immunology / Adenovirus / Adenoviruses / Adolescent / Adult / Africa, Eastern / AIDS vaccines / AIDS Vaccines - administration & dosage / AIDS Vaccines - adverse effects / AIDS Vaccines - genetics / AIDS Vaccines - immunology / Antibodies, Neutralizing - blood / Antibodies, Neutralizing - immunology / Antibodies, Viral - blood / Antibodies, Viral - immunology / Antigens / Antigens, Viral - immunology / Applied microbiology / Biological and medical sciences / CD4-Positive T-Lymphocytes - immunology / CD8-Positive T-Lymphocytes - immunology / Cells, Cultured / DNA, Viral - genetics / DNA, Viral - immunology / Double-Blind Method / Enzyme-Linked Immunosorbent Assay / Female / Fundamental and applied biological sciences. Psychology / Genetic vectors / HIV / HIV 1 / HIV Infections - immunology / HIV Infections - prevention & control / HIV-1 - genetics / HIV-1 - immunology / HIV/AIDS / Human immunodeficiency virus 1 / Human Immunodeficiency Virus Proteins - genetics / Human Immunodeficiency Virus Proteins - immunology / Humans / Infectious diseases / Interferon-gamma - metabolism / Leukocytes, Mononuclear - immunology / Male / Medical sciences / Microbiology / Middle Aged / Miscellaneous / Placebos / Plasmids / Plasmids - genetics / Plasmids - immunology / Vaccination / Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects) / Vaccines, DNA - administration & dosage / Vaccines, DNA - adverse effects / Vaccines, DNA - genetics / Vaccines, DNA - immunology / Virology / Volunteerism / Young Adult