Adenovirus Vector-Induced Immune Responses in Nonhuman Primates: Responses to Prime Boost Regimens

• Published in: The Journal of immunology (1950) Vol. 182; no. 10; pp. 6587 - 6599
• Main Authors: Tatsis, Nia, Lasaro, Marcio O, Lin, Shih-Wen, Xiang, Zhi Q, Zhou, Dongming, DiMenna, Lauren, Li, Hua, Bian, Ang, Abdulla, Sarah, Li, Yan, Giles-Davis, Wynetta, Engram, Jessica, Ratcliffe, Sarah J, Silvestri, Guido, Ertl, Hildegund C, Betts, Michael R
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15.05.2009
• Subjects: Adenoviridae - genetics; Adenoviridae - immunology; AIDS Vaccines - immunology; Animals; Antibodies, Viral - blood; Antibodies, Viral - immunology; Enzyme-Linked Immunosorbent Assay; Genetic Vectors - genetics; Genetic Vectors - immunology; Human Immunodeficiency Virus Proteins - genetics; Human Immunodeficiency Virus Proteins - immunology; Immunization, Secondary - methods; Interferon-gamma - biosynthesis; Interleukin-2 - biosynthesis; Lymphocyte Activation - immunology; Macaca mulatta; Pan troglodytes; Polymerase Chain Reaction; T-Lymphocytes - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.0900317

In the phase IIb STEP trial an HIV-1 vaccine based on adenovirus (Ad) vectors of the human serotype 5 (AdHu5) not only failed to induce protection but also increased susceptibility to HIV-1 infection in individuals with preexisting neutralizing Abs against AdHu5. The mechanisms underlying the increased HIV-1 acquisition rates have not yet been elucidated. Furthermore, it remains unclear if the lack of the vaccine's efficacy reflects a failure of the concept of T cell-mediated protection against HIV-1 or a product failure of the vaccine. Here, we compared two vaccine regimens based on sequential use of AdHu5 vectors or two different chimpanzee-derived Ad vectors in rhesus macaques that were AdHu5 seropositive or seronegative at the onset of vaccination. Our results show that heterologous booster immunizations with the chimpanzee-derived Ad vectors induced higher T and B cell responses than did repeated immunizations with the AdHu5 vector, especially in AdHu5-preexposed macaques.