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J. Virol. doi:10.1128/JVI.02216-07
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Differential CD4⁺ versus CD8⁺ T-cell responses elicited by different Poxvirus-based HIV-1 vaccine candidates provide comparable efficacy in primates

Department of Virology, Biomedical Primate Research Center, 2288 GJ Rijswijk, The Netherlands, Institut für Medizinische Mikrobiologie und Hygiene der Universität Regensburg, 39053, Germany, Department of Cell and Molecular Biology, Centro Nacional de Biotecnologia, CSIC, Madrid, 28049, Spain, and the University of Cambridge, Department of Veterinary Medicine, Cambridge, CB3 0ES, UK

^* To whom correspondence should be addressed. Email: mooij{at}bprc.nl.

	Abstract

Poxvirus vectors have proven to be highly effective for boosting immune responses in diverse vaccine settings. Recent reports reveal marked differences in 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-1 model of AIDS in Indian rhesus macaques. Differences in the immune responses in outbred animals were not distinguished by ELISpot, but by multiparameter FACS analysis, revealing a difference in the number of animals responding with both CD4⁺ as well as CD8⁺ T-cell responses to vaccine inserts (MVA), to those which 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 post-challenge, and even accompanied antigenic modulation throughout control of chronic infection. Importantly, strong pre-exposure HIV-1/Simian Immunodeficiency Virus (SIV)-specific CD4⁺ T-cell responses did not prove deleterious with respect to accelerated disease progression. In contrast, in this setting strong vaccine induced polyfunctional CD4⁺ T-cell responses were capable of eliciting similar efficacy as those generating stronger CD8⁺ T-cell responses.