Group M-based HIV-1 Gag peptides are frequently targeted by T cells in chronically infected US and Zambian patients

• Published in: AIDS (London) Vol. 20; no. 3; pp. 353 - 360
• Main Authors: Bansal, Anju, Gough, Ethan, Ritter, Doug, Wilson, Craig, Mulenga, Joseph, Allen, Susan, Goepfert, Paul A
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 14.02.2006
• Subjects: AIDS Vaccines; Biological and medical sciences; Enzyme-Linked Immunosorbent Assay; Female; Genes, gag - immunology; HIV Infections - immunology; HIV-1 - immunology; Human immunodeficiency virus 1; Human viral diseases; Humans; Immunity, Cellular; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunopathology; Infectious diseases; Male; Medical sciences; T-Lymphocytes - immunology; United States; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Zambia; Zambia; Africa; United States; USA; HIV-1 sequence; Peptides; HIV-1 virus; Prevention; Microbiological investigation; Gag protein; Immunological investigation; T-Lymphocyte; Target cell; Infected cell; Human; Immunopathology; Typing; Retroviridae; AIDS; Vaccine; cross subtype recognition; Immune deficiency; Lentivirus; Infection; Virus; consensus; Immunoprophylaxis; ancestral; Viral disease; Human immunodeficiency virus; Subtype
• ISSN: 0269-9370
• DOI: 10.1097/01.aids.0000206501.16783.67

The enormous sequence diversity of HIV-1 has been a major obstacle in the development of a globally useful vaccine for AIDS. The consensus and ancestral sequence-based immunogens minimize the genetic distance between contemporary isolates and vaccine strains. Hence these sequences may be promising candidates for HIV vaccines or serve as a universal reagent set for evaluating Gag-specific responses. In this study, we measured the T-cell reactivity to consensus (subtype A, B, C and group M), ancestral (group M and subtype B) and HXB2 Gag peptides (15-mers overlapping by 11) in HIV-1-infected subjects from two reference populations. We evaluated the Gag-specific T-cell responses in 43 chronically infected US (subtype B) and 13 Zambian (subtype C) subjects using an interferon-gamma enzyme-linked immunosorbent spot assay. Our findings demonstrate a broad cross-reactivity of nearly 70% among all the seven Gag immunogens evaluated. Consensus M sequences elicited similar levels of responses as did the consensus B, ancestral subtype B and HXB2 peptides in subtype B-infected US patients. In subtype C-infected Zambian subjects, responses of similar breadth and magnitude were elicited by consensus C, consensus M and ancestral M peptides. Our data demonstrate that peptide pools based on consensus or ancestral M-based sequences can be used to evaluate Gag-specific responses elicited by subtype B or subtype C-based immunogens.