Adenovirus-specific immunity after immunization with an Ad5 HIV-1 vaccine candidate in humans

• Published in: Nature medicine Vol. 15; no. 8; pp. 873 - 875
• Main Authors: O'Brien, Kara L, Liu, Jinyan, King, Sharon L, Sun, Ying-Hua, Schmitz, Joern E, Lifton, Michelle A, Hutnick, Natalie A, Betts, Michael R, Dubey, Sheri A, Goudsmit, Jaap, Shiver, John W, Robertson, Michael N, Casimiro, Danilo R, Barouch, Dan H
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.08.2009; Nature Publishing Group
• Subjects: Acquired Immunodeficiency Syndrome - immunology; Acquired Immunodeficiency Syndrome - therapy; Adenoviridae - immunology; Adenovirus; Adenoviruses; AIDS vaccines; AIDS Vaccines - immunology; AIDS Vaccines - therapeutic use; Antibodies, Viral - analysis; Antibodies, Viral - blood; Antibody Specificity - immunology; Biomedical and Life Sciences; Biomedicine; brief-communication; Cancer Research; Health aspects; HIV; HIV infection; HIV-1 - immunology; Human immunodeficiency virus; Human immunodeficiency virus 1; Humans; Immune system; Immunization; Infectious Diseases; Interferon-gamma - metabolism; Lymphocytes; Medical research; Metabolic Diseases; Molecular Medicine; Neurosciences; Physiological aspects; Prevention; Risk factors; T cells; T-Cell Antigen Receptor Specificity - immunology; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Vaccines; Vaccines, Synthetic - immunology; Vaccines, Synthetic - therapeutic use; United States
• ISSN: 1078-8956; 1546-170X; 1546-170X
• DOI: 10.1038/nm.1991

The phase 2b trial of Merck's recombinant adenovirus type 5–based HIV-1 vaccine was halted as the vaccine seemed to have increased HIV-1 acquisition in vaccine recipients who had preexisting immunity to the adenovirus vector. One theory to explain these results is that the preexisting antibody response to the vector may have been a surrogate for increased vector-specific CD4 + T cells, which would have been amplified after vaccination and may have served as increased target cells during subsequent HIV-1 exposure. Daniel Barouch and his colleagues and Michael Betts and his colleagues now challenge this view. The immunologic basis for the potential enhanced HIV-1 acquisition in adenovirus serotype 5 (Ad5)-seropositive individuals who received the Merck recombinant Ad5 HIV-1 vaccine in the STEP study remains unclear. Here we show that baseline Ad5-specific neutralizing antibodies are not correlated with Ad5-specific T lymphocyte responses and that Ad5-seropositive subjects do not develop higher vector-specific cellular immune responses as compared with Ad5-seronegative subjects after vaccination. These findings challenge the hypothesis that activated Ad5-specific T lymphocytes were the cause of the potential enhanced HIV-1 susceptibility in the STEP study.