Qualitative T-helper responses to multiple viral antigens correlate with vaccine-induced immunity to simian/human immunodeficiency virus infection

Mooij, Petra and Nieuwenhuis, Ivonne G. and Knoop, Christiaan J. and Doms, Robert W. and Bogers, Willy M. J. M. and Ten Haaft, Peter J. F. and Niphuis, Henk and Koornstra, Wim and Bieler, Kurt and Koestler, Josef and Morein, Bror and Cafaro, Aurelio and Ensoli, Barbara and Wagner, Ralf and Heeney, Jonathan L. (2004) Qualitative T-helper responses to multiple viral antigens correlate with vaccine-induced immunity to simian/human immunodeficiency virus infection. JOURNAL OF VIROLOGY, 78 (7). pp. 3333-3342. ISSN 0022-538X

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Abstract

Evidence is accumulating that CD4(+) T-helper (Th) responses play a critical role in facilitating effector responses which are capable of controlling and even preventing human immunodeficiency virus (HIV) infection. The present work was undertaken to determine whether immunization with multiple antigens influenced individual Th responses and increased protection relative to a single antigen. Rhesus macaques were primed with DNA and boosted (immune-stimulating complex-formulated protein) with a combination of regulatory and structural antigens (Tat-Env-Gag) or with Tat alone. Immunization with combined antigens reduced the magnitude of the responses to Tat compared to the single-antigen immunization. Interestingly, the Th immune responses to the individual antigens were noticeably different. To determine whether the qualitative differences in vaccine-induced Th responses correlated with vaccine efficacy, animals were challenged intravenously with simian/human immunodeficiency virus (strain SHIV89.6p) 2 months following the final immunization. Animals that developed combined Th1- and Th2-like responses to Gag and Th2 dominant Env-specific responses were protected from disease progression. Interestingly, one animal that was completely protected from infection had the strongest IFN-gamma and interleukin-2 (IL-2) responses prior to challenge, in addition to very strong IL-4 responses to Gag and Env. In contrast, animals with only a marked vaccine-induced Tat-specific Th2 response (no IFN-gamma) were not protected from infection or disease. These data support the rationale that effective HIV vaccine-induced immunity requires a combination of potent Th1- and Th2-like responses best directed to multiple antigens.

Item Type: Article
Uncontrolled Keywords: RHESUS-MONKEYS; CORECEPTOR USAGE; NEUTRALIZING ANTIBODIES; LYMPHOCYTE RESPONSES; CYNOMOLGUS MONKEYS; CD8-T-CELL MEMORY; DNA VACCINATION; CD4-T-CELL HELP; 89.6P CHALLENGE; PROTEIN VACCINE;
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene
Depositing User: Dr. Gernot Deinzer
Date Deposited: 26 Jul 2021 06:01
Last Modified: 26 Jul 2021 06:01
URI: https://pred.uni-regensburg.de/id/eprint/37820

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