Safety and immunogenicity study of Multiclade HIV-1 adenoviral vector vaccine alone or as boost following a multiclade HIV-1 DNA vaccine in Africa

• Published in: PloS one Vol. 5; no. 9; p. e12873
• Main Authors: Jaoko, Walter, Karita, Etienne, Kayitenkore, Kayitesi, Omosa-Manyonyi, Gloria, Allen, Susan, Than, Soe, Adams, Elizabeth M, Graham, Barney S, Koup, Richard A, Bailer, Robert T, Smith, Carol, Dally, Len, Farah, Bashir, Anzala, Omu, Muvunyi, Claude M, Bizimana, Jean, Tarragona-Fiol, Tony, Bergin, Philip J, Hayes, Peter, Ho, Martin, Loughran, Kelley, Komaroff, Wendy, Stevens, Gwynneth, Thomson, Helen, Boaz, Mark J, Cox, Josephine H, Schmidt, Claudia, Gilmour, Jill, Nabel, Gary J, Fast, Patricia, Bwayo, Job
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 21.09.2010; Public Library of Science (PLoS)
• Subjects: Acquired immune deficiency syndrome; Adenoviridae - genetics; Adenoviridae - immunology; Adenoviruses; Adolescent; Adult; Adults; AIDS; AIDS vaccines; AIDS Vaccines - adverse effects; AIDS Vaccines - immunology; Antibodies; Antibodies, Viral - immunology; Antigens; Biological response modifiers; Deoxyribonucleic acid; DNA; DNA vaccines; Dosage; Double-Blind Method; Drug-Related Side Effects and Adverse Reactions; Enzyme-linked immunosorbent assay; Epidemiology; gag Gene Products, Human Immunodeficiency Virus - adverse effects; gag Gene Products, Human Immunodeficiency Virus - genetics; gag Gene Products, Human Immunodeficiency Virus - immunology; Genetic research; Genetic Vectors - adverse effects; Genetic Vectors - genetics; Genetic Vectors - immunology; Health aspects; HIV; HIV antigens; HIV infections; HIV Infections - immunology; HIV Infections - prevention & control; HIV Infections - virology; HIV-1 - classification; HIV-1 - genetics; HIV-1 - immunology; Human immunodeficiency virus; Humans; Immune response; Immune response (humoral); Immune system; Immunity; Immunization, Secondary; Immunogenicity; Immunoglobulins; Immunology; Immunology/Immune Response; Infections; Infectious diseases; Infectious Diseases/HIV Infection and AIDS; Interferon; Laboratories; Lymphocytes; Male; Medical research; Middle Aged; Nef protein; pol Gene Products, Human Immunodeficiency Virus - adverse effects; pol Gene Products, Human Immunodeficiency Virus - genetics; pol Gene Products, Human Immunodeficiency Virus - immunology; Priming; Proteins; Public health; Public Health and Epidemiology/Immunization; Randomization; Safety; Safety and security measures; Vaccines; Vaccines, DNA - adverse effects; Vaccines, DNA - immunology; Young Adult; γ-Interferon; New York; San Francisco California; Kenya; United States > US; Maryland
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0012873

We conducted a double-blind, randomized, placebo-controlled Phase I study of a recombinant replication-defective adenovirus type 5 (rAd5) vector expressing HIV-1 Gag and Pol from subtype B and Env from subtypes A, B and C, given alone or as boost following a DNA plasmid vaccine expressing the same HIV-1 proteins plus Nef, in 114 healthy HIV-uninfected African adults. Volunteers were randomized to 4 groups receiving the rAd5 vaccine intramuscularly at dosage levels of 1×10(10) or 1×10(11) particle units (PU) either alone or as boost following 3 injections of the DNA vaccine given at 4 mg/dose intramuscularly by needle-free injection using Biojector® 2000. Safety and immunogenicity were evaluated for 12 months. Both vaccines were well-tolerated. Overall, 62% and 86% of vaccine recipients in the rAd5 alone and DNA prime - rAd5 boost groups, respectively, responded to the HIV-1 proteins by an interferon-gamma (IFN-γ) ELISPOT. The frequency of immune responses was independent of rAd5 dosage levels. The highest frequency of responses after rAd5 alone was detected at 6 weeks; after DNA prime - rAd5 boost, at 6 months (end of study). At baseline, neutralizing antibodies against Ad5 were present in 81% of volunteers; the distribution was similar across the 4 groups. Pre-existing immunity to Ad5 did not appear to have a significant impact on reactogenicity or immune response rates to HIV antigens by IFN-γ ELISPOT. Binding antibodies against Env were detected in up to 100% recipients of DNA prime - rAd5 boost. One volunteer acquired HIV infection after the study ended, two years after receipt of rAd5 alone. The HIV-1 rAd5 vaccine, either alone or as a boost following HIV-1 DNA vaccine, was well-tolerated and immunogenic in African adults. DNA priming increased the frequency and magnitude of cellular and humoral immune responses, but there was no effect of rAd5 dosage on immunogenicity endpoints. ClinicalTrials.gov NCT00124007.