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Journal of Virology, March 2008, p. 2975-2988, Vol. 82, No. 6
0022-538X/08/$08.00+0     doi:10.1128/JVI.02216-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Differential CD4+ versus CD8+ T-Cell Responses Elicited by Different Poxvirus-Based Human Immunodeficiency Virus Type 1 Vaccine Candidates Provide Comparable Efficacies in Primates{triangledown} ,{dagger}

Petra Mooij,1* Sunita S. Balla-Jhagjhoorsingh,1,{ddagger} Gerrit Koopman,1 Niels Beenhakker,1 Patricia van Haaften,1,§ Ilona Baak,1,¶ Ivonne G. Nieuwenhuis,1 Ivanela Kondova,1 Ralf Wagner,2 Hans Wolf,2 Carmen E. Gómez,3 José L. Nájera,3 Victoria Jiménez,3 Mariano Esteban,3 and Jonathan L. Heeney1,4

Department of Virology, Biomedical Primate Research Center, 2288 GJ Rijswijk, The Netherlands,1 Institut für Medizinische Mikrobiologie und Hygiene der Universität Regensburg 39053, Germany,2 Department of Cell and Molecular Biology, Centro Nacional de Biotecnologia, CSIC, Madrid 28049, Spain,3 the University of Cambridge, Department of Veterinary Medicine, Cambridge CB3 0ES, United Kingdom4

Received 11 October 2007/ Accepted 13 December 2007

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.

* Corresponding author. Mailing address: Department of Virology, Biomedical Primate Research Centre (BPRC), P.O. Box 3306, 2280 GH Rijswijk, The Netherlands. Phone: 31 152842615. Fax: 31 152842601. E-mail: mooij{at}bprc.nl

{triangledown} Published ahead of print on 9 January 2008.

{dagger} Supplemental material for this article may be found at http://jvi.asm.org/.

{ddagger} Present address: Institute of Tropical Medicine, B2000 Antwerp, Belgium.

§ Present address: LUMC, 2300 RC Leiden, The Netherlands.

Present address: NFI, 2497 BG The Hague, The Netherlands.

Journal of Virology, March 2008, p. 2975-2988, Vol. 82, No. 6
0022-538X/08/$08.00+0     doi:10.1128/JVI.02216-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Mooij, P., Balla-Jhagjhoorsingh, S. S., Beenhakker, N., van Haaften, P., Baak, I., Nieuwenhuis, I. G., Heidari, S., Wolf, H., Frachette, M.-J., Bieler, K., Sheppard, N., Harari, A., Bart, P.-A., Liljestrom, P., Wagner, R., Pantaleo, G., Heeney, J. L. (2009). Comparison of Human and Rhesus Macaque T-Cell Responses Elicited by Boosting with NYVAC Encoding Human Immunodeficiency Virus Type 1 Clade C Immunogens. J. Virol. 83: 5881-5889 [Abstract] [Full Text]  
  • Burgers, W. A., Chege, G. K., Muller, T. L., van Harmelen, J. H., Khoury, G., Shephard, E. G., Gray, C. M., Williamson, C., Williamson, A.-L. (2009). Broad, high-magnitude and multifunctional CD4+ and CD8+ T-cell responses elicited by a DNA and modified vaccinia Ankara vaccine containing human immunodeficiency virus type 1 subtype C genes in baboons. J. Gen. Virol. 90: 468-480 [Abstract] [Full Text]  


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