title: Differential CD4+ versus CD8+ T-cell responses elicited by different poxvirus-based human immunodeficiency virus type 1 vaccine candidates provide comparable efficacies in primates.
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 1 (HIV-1) model of AIDS in Indian rhesus macaques. Differences in the immune responses in outbred animals were not distinguished by enzyme-linked 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.
authors.affiliation: Department of Virology, Biomedical Primate Research Centre (BPRC), P.O. Box 3306, 2280 GH Rijswijk, The Netherlands. mooij@bprc.nl
authors.forename: Petra
authors.initials: P
authors.lastname: Mooij
authors.forename: Sunita S
authors.initials: SS
authors.lastname: Balla-Jhagjhoorsingh
authors.forename: Gerrit
authors.initials: G
authors.lastname: Koopman
authors.forename: Niels
authors.initials: N
authors.lastname: Beenhakker
authors.forename: Patricia
authors.initials: P
authors.lastname: van Haaften
authors.forename: Ilona
authors.initials: I
authors.lastname: Baak
authors.forename: Ivonne G
authors.initials: IG
authors.lastname: Nieuwenhuis
authors.forename: Ivanela
authors.initials: I
authors.lastname: Kondova
authors.forename: Ralf
authors.initials: R
authors.lastname: Wagner
authors.forename: Hans
authors.initials: H
authors.lastname: Wolf
authors.forename: Carmen E
authors.initials: CE
authors.lastname: Gómez
authors.forename: José L
authors.initials: JL
authors.lastname: Nájera
authors.forename: Victoria
authors.initials: V
authors.lastname: Jiménez
authors.forename: Mariano
authors.initials: M
authors.lastname: Esteban
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Heeney
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D015488:HIV Antigens / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D016130:Immunophenotyping; D008253:Macaca mulatta; D011212:Poxviridae / Q000235:genetics / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D015488:HIV Antigens