Delayed-type hypersensitivity responses to HIV Gag p24 relate to clinical outcome after peptide-based therapeutic immunization for chronic HIV infection

• Published in: APMIS : acta pathologica, microbiologica et immunologica Scandinavica Vol. 120; no. 3; pp. 204 - 209
• Main Authors: KRAN, ANNE-MARTE B., SOMMERFELT, MAJA A., BAKSAAS, INGEBJØRG, SØRENSEN, BIRGER, KVALE, DAG
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.03.2012; Blackwell; Wiley Subscription Services, Inc
• Subjects: AIDS Vaccines - administration & dosage; AIDS Vaccines - immunology; antiretroviral therapy; Antiviral agents; Applied microbiology; Biological and medical sciences; CD4-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - immunology; Chronic infection; Clinical trials; Cohort Studies; Data processing; delayed-type hypersensitivity reaction; Dendritic cells; Follow-Up Studies; Fundamental and applied biological sciences. Psychology; Gag protein; gamma -Interferon; HIV; HIV Core Protein p24 - immunology; HIV Infections - immunology; HIV Infections - therapy; HIV-1 - immunology; Human immunodeficiency virus; Human viral diseases; Humans; Hypersensitivity (delayed); Hypersensitivity, Delayed - immunology; Immune response; Immunity, Cellular - immunology; Immunization; Immunization - methods; Infectious diseases; Interferon-gamma - blood; Interferon-gamma - immunology; Interleukin 10; Interleukin-10 - blood; Interleukin-10 - immunology; Kaplan-Meier Estimate; Lymphocytes T; Medical sciences; Microbiology; Miscellaneous; Peptides; Prospective Studies; RNA, Viral - blood; Skin tests; T-cell responses; therapeutic immunization; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Virology; Allergy; Immunopathology; Immunization; Prognosis; Peptides; T-cell responses; Retroviridae; AIDS; Delayed hypersensitivity; Cellular immunity; Vaccine; Immune deficiency; Lentivirus; therapeutic immunization; Infection; Virus; Chronic; delayed-type hypersensitivity reaction; Immunology; HIV; Viral disease; Human immunodeficiency virus
• ISSN: 0903-4641; 1600-0463
• DOI: 10.1111/j.1600-0463.2011.02843.x

Kran A‐MB, Sommerfelt MA, Baksaas I, Sørensen B, Kvale D. Delayed‐type hypersensitivity responses to HIV Gag p24 relate to clinical outcome after peptide‐based therapeutic immunization for chronic HIV infection. APMIS 2012; 120: 204–9. Therapeutic immunization in chronic HIV infection aims to induce durable, HIV‐specific immune responses capable of controlling disease progression, but immunological correlates of clinical efficacy are poorly defined. We have previously immunized 38 patients with a mixture of four short Gag p24‐like conserved peptides (Vacc‐4x) targeting skin dendritic cells. Antiretroviral treatment (ART) was initially stopped after completed immunizations and resumed post‐protocol during regular clinical follow‐up according to current guidelines. Four years after enrolment, Vacc‐4x‐specific cellular responses were evaluated in vivo by delayed‐type hypersensitivity (DTH) skin test, and in vitro by a T‐cell proliferation assay. Kaplan–Meier product‐limit estimates were used to analyse time until ART was resumed. Peptide‐specific cellular immune responses induced by Vacc‐4x had persisted 4 years after the last immunization in terms of unchanged DTH independent of ART and detectable proliferative T‐cell responses which correlated to the native peptides (R = 0.73, p = 0.01). Circulating bifunctional (IFN‐γ and IL‐10) Vacc‐4x‐specific T‐cell clones were detected in 43% of patients. Subjects with the strongest post‐immunization DTH responses appeared to start ART later compared with DTH low responders (p = 0.07). These data suggest that DTH responses should be further evaluated as a new and convenient tool for predicting clinical efficacy in trials testing therapeutic immunizations.