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Journal of Virology, June 2009, p. 5881-5889, Vol. 83, No. 11
0022-538X/09/$08.00+0 doi:10.1128/JVI.02345-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
Comparison of Human and Rhesus Macaque T-Cell Responses Elicited by Boosting with NYVAC Encoding Human Immunodeficiency Virus Type 1 Clade C Immunogens
Petra Mooij,1
Sunita S. Balla-Jhagjhoorsingh,1
Niels Beenhakker,1
Patricia van Haaften,1
Ilona Baak,1
Ivonne G. Nieuwenhuis,1
Shirin Heidari,2
Hans Wolf,3
Marie-Joelle Frachette,4
Kurt Bieler,3
Neil Sheppard,6
Alexandre Harari,5
Pierre-Alexandre Bart,5
Peter Liljeström,2
Ralf Wagner,3
Giuseppe Pantaleo,5 and
Jonathan L. Heeney1,7*
Department of Virology, Biomedical Primate Research Centre (BPRC), Rijswijk, The Netherlands,1 Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, S-171 77 Stockholm, Sweden,2 Department of Molecular Microbiology and Gene Therapy, Institute of Medical Microbiology and Hygiene, University Regensburg, D-93053 Regensburg, Germany,3 Sanofi Pasteur, 69280 Marcy l'Etoile, France,4 Department of Medicine, Division of Immunology and Allergy, Laboratory of AIDS Immunopathogenesis, Centre Hospitalier Universitaire Vaudois, University of Lausanne, 1011 Lausanne, Switzerland,5 Department of Molecular Retrovirology, The Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom,6 Department of Veterinary Medicine, University of Cambridge, Cambridge CB3 OES, United Kingdom7
Received 11 November 2008/ Accepted 17 March 2009
Rhesus macaques (Macaca mulatta) have played a valuable role in the development of human immunodeficiency virus (HIV) vaccine candidates prior to human clinical trials. However, changes and/or improvements in immunogen quality in the good manufacturing practice (GMP) process or changes in adjuvants, schedule, route, dose, or readouts have compromised the direct comparison of T-cell responses between species. Here we report a comparative study in which T-cell responses from humans and macaques to HIV type 1 antigens (Gag, Pol, Nef, and Env) were induced by the same vaccine batches prepared under GMP and administered according to the same schedules in the absence and presence of priming. Priming with DNA (humans and macaques) or alphavirus (macaques) and boosting with NYVAC induced robust and broad antigen-specific responses, with highly similar Env-specific gamma interferon (IFN-
) enzyme-linked immunospot assay responses in rhesus monkeys and human volunteers. Persistent cytokine responses of antigen-specific CD4+ and CD8+ T cells of the central memory as well as the effector memory phenotype, capable of simultaneously eliciting multiple cytokines (IFN-, interleukin 2, and tumor necrosis factor alpha), were induced. Responses were highly similar in humans and primates, confirming earlier data indicating that priming is essential for inducing robust NYVAC-boosted IFN- T-cell responses. While significant similarities were observed in Env-specific responses in both species, differences were also observed with respect to responses to other HIV antigens. Future studies with other vaccines using identical lots, immunization schedules, and readouts will establish a broader data set of species similarities and differences with which increased confidence in predicting human responses may be achieved.
* Corresponding author. Mailing address: University of Cambridge, Madingley Road, Cambridge CB3 OES, United Kingdom. Phone: 44 1223 766250. Fax: 44 1223 337671. E-mail: jlh66{at}cam.ac.uk
Published ahead of print on 25 March 2009.
Journal of Virology, June 2009, p. 5881-5889, Vol. 83, No. 11
0022-538X/09/$08.00+0 doi:10.1128/JVI.02345-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
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