Differential CD4(+) versus CD8(+) T-cell responses elicited by different poxvirus-based human immunodeficiency virus type I vaccine candidates provide comparable efficacies in primates

Mooij, Petra and Alla-Jhagjhoorsingh, Sunita S. and Koopman, Gerrit and Beenhakker, Niels and van Haaften, Patricia and Baak, Ilona and Nieuwenhuis, Ivonne G. and Kondova, Ivanela and Wagner, Ralf and Wolf, Hans and Gomez, Carmen E. and Najera, Jose L. and Jimenez, Victoria and Esteban, Mariano and Heeney, Jonathan L. (2008) Differential CD4(+) versus CD8(+) T-cell responses elicited by different poxvirus-based human immunodeficiency virus type I vaccine candidates provide comparable efficacies in primates. JOURNAL OF VIROLOGY, 82 (6). pp. 2975-2988. ISSN 0022-538X, 1098-5514

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Abstract

Poxvirus vectors have proven to be highly effective for boosting immune responses in diverse vaccine settings. Recent reports reveal marked differences in the gene expression of human dendritic cells infected with two leading poxvirus-based human immunodeficiency virus (HIV) vaccine candidates, New York vaccinia virus (NYVAC) and modified vaccinia virus Ankara (MVA). To understand how complex genomic changes in these two vaccine vectors translate into antigen-specific systemic immune responses, we undertook a head-to-head vaccine immunogenicity and efficacy study in the pathogenic HIV type I (HIV-1) model of AIDS in Indian rhesus macaques. Differences in the immune responses in outbred animals were not distinguished by enzymelinked immunospot assays, but differences were distinguished by multiparameter fluorescence-activated cell sorter analysis, revealing a difference between the number of animals with both CD4(+) and CD8(+) T-cell responses to vaccine inserts (MVA) and those that elicit a dominant CD4(+) T-cell response (NYVAC). Remarkably, vector-induced differences in CD4(+)/CD8(+) T-cell immune responses persisted for more than a year after challenge and even accompanied antigenic modulation throughout the control of chronic infection. Importantly, strong preexposure HIV-1/simian immunodeficiency virus-specific CD4(+) T-cell responses did not prove deleterious with respect to accelerated disease progression. In contrast, in this setting, animals with strong vaccine-induced polyfunctional CD4(+) T-cell responses showed efficacies similar to those with stronger CD8(+) T-cell responses.

Item Type: Article
Uncontrolled Keywords: SIMIAN IMMUNODEFICIENCY; RHESUS-MONKEYS; DNA PRIME; DENDRITIC CELLS; AIDS VACCINE; LYMPHOCYTE RESPONSES; DISEASE PROGRESSION; PROTECTIVE EFFICACY; MUCOSAL CHALLENGE; IMMUNE-RESPONSES;
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene
Depositing User: Petra Gürster
Date Deposited: 13 Jan 2021 10:53
Last Modified: 13 Jan 2021 10:53
URI: https://pred.uni-regensburg.de/id/eprint/31291

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