Low frequency of amino acid alterations following therapeutic immunization with HIV-1 Gag p24-like peptides

• Published in: AIDS (London) Vol. 24; no. 17; pp. 2609 - 2618
• Main Authors: KRAN, Anne-Marte B, JONASSEN, Tom Øystein, SOMMERFELT, Maja A, LØVGARDEN, Gunilla, SØRENSEN, Birger, KVALE, Dag
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 13.11.2010
• Subjects: AIDS Vaccines - administration & dosage; AIDS/HIV; Biological and medical sciences; CD4-Positive T-Lymphocytes - immunology; Female; HIV Core Protein p24 - immunology; HIV Infections - drug therapy; HIV Infections - immunology; HIV-1 - immunology; Human immunodeficiency virus 1; Human viral diseases; Humans; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunopathology; Infectious diseases; Male; Medical sciences; Peptides; Prospective Studies; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Viremia - immunology; HIV-1; Immunopathology; Peptides; HIV-1 virus; Retroviridae; amino acid substitutions; AIDS; Cellular immunity; immune escape; Immune deficiency; Lentivirus; Low frequency; therapeutic immunizations; Infection; Virus; Treatment; Immunological investigation; Viral disease; Aminoacid; Immunotherapy; gag protein p24; Human immunodeficiency virus
• ISSN: 0269-9370; 1473-5571
• DOI: 10.1097/QAD.0b013e32833e502b

In chronic HIV-1 infection, the efficacy of a cellular immune response may decline if the virus evolves into variants not recognized by host immune response. The aim of this study was to explore HIV-1 immune escape mutations imposed by therapeutic immunization by investigating sequence variations that might contribute to relapse of viremia in an immunized, HIV-1-infected cohort. We have previously immunized HIV-1-infected individuals on antiretroviral therapy (ART) with a mixture of four short peptides (Vacc-4x) corresponding to p24. Long postimmunization periods without ART allowed longitudinal sequence studies of regions corresponding to Vacc-4x. Regions of gag p24 including the locations of the Vacc-4x peptides, were sequenced before start of ART, and after postimmunization ART stop (n = 27). Rates and locations of amino acid substitutions were then related to peptide-specific T-cell responses and known epitopes presented by Vacc-4x. The overall rate of amino acid substitutions was low during 35 months (median) of postimmunization viremia, with similar rates of substitution within the regions corresponding to Vacc-4x peptides and other p24 regions despite durable Vacc-4x-specific T-cell responses. Postimmunization amino acid substitutions within Vacc-4x regions were detected in only six patients, and only two of them had measurable T-cell responses against the relevant peptide. The results suggested low prevalence of evolutionary selection of p24 despite new and long-lasting Vacc-4x-specific T-cell responses. The conserved Vacc-4x sequences might therefore be particularly suited for therapeutic immunization. Generally, studies of longitudinal sequence variations after immunization might be valuable when assessing immune escape in HIV vaccine trials.