Baseline Ad5 serostatus does not predict Ad5 HIV vaccine–induced expansion of adenovirus-specific CD4+ T cells

• Published in: Nature medicine Vol. 15; no. 8; pp. 876 - 878
• Main Authors: Hutnick, Natalie A, Carnathan, Diane G, Dubey, Sheri A, Makedonas, George, Cox, Kara S, Kierstead, Lisa, Ratcliffe, Sarah J, Robertson, Michael N, Casimiro, Danilo R, Ertl, Hildegund C J, Betts, Michael R
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.08.2009; Nature Publishing Group
• Subjects: Acquired Immunodeficiency Syndrome - blood; Acquired Immunodeficiency Syndrome - diagnosis; Acquired Immunodeficiency Syndrome - immunology; Acquired Immunodeficiency Syndrome - therapy; Adenoviridae - immunology; Adenoviruses; AIDS Vaccines - immunology; Antibodies, Viral - blood; Antibody response; Biomedical and Life Sciences; Biomedicine; brief-communication; Cancer Research; CD4 antigen; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes - immunology; Cell Proliferation; Clinical outcomes; Clinical trials; Expression vectors; HIV; HIV-1 - immunology; Human immunodeficiency virus; Humans; Immune system; Infectious Diseases; Lymphocytes; Lymphocytes T; Metabolic Diseases; Molecular Medicine; Neurosciences; Prognosis; T-Cell Antigen Receptor Specificity - immunology; Vaccines; Vaccines, Synthetic - immunology
• ISSN: 1078-8956; 1546-170X; 1546-170X
• DOI: 10.1038/nm.1989

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 mechanisms underlying possible increased HIV-1 acquisition in adenovirus 5 (Ad5)-seropositive subjects vaccinated with Ad5–HIV-1 vectors in the Merck STEP trial remain unclear. We find that Ad5 serostatus does not predict Ad5-specific CD4 + T cell frequency, and we did not observe durable significant differences in Ad5-specific CD4 + T cells between Ad5-seropositive and Ad5-seronegative subjects after vaccination. These findings indicate no causative role for Ad5-specific CD4 + T cells in increasing HIV-1 susceptibility in the STEP trial.