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Susceptibility to Simian Immunodeficiency Virus Ex Vivo Predicts Outcome of a Prime-Boost Vaccine After SIVmac239 Challenge

Ochieng, Washingtone PhD*; Sauermann, Ulrike PhD*; Schulte, Reiner PhD*; Suh, You-Suk PhD*†; Kim, Kwang Soon; Sung, Young C PhD; Hunsmann, Gerhard MD*; Stahl-Hennig, Christiane DVM*; Sopper, Sieghart PhD*

JAIDS Journal of Acquired Immune Deficiency Syndromes: October 2009 - Volume 52 - Issue 2 - p 162-169
doi: 10.1097/QAI.0b013e3181b22f4a
Basic Science

Background: Efficacy assessment of AIDS vaccines relies both on preclinically challenging immunized monkeys with simian immunodeficiency virus (SIV) or monitoring infection rates in large human trials. Although conventional parameters of vaccine-induced immune responses do not completely predict outcome, existing methods for testing cellular immunity are sophisticated and difficult to establish in resource-limited settings.

Methods: We have used virus replication kinetics (VVR) on ConA-stimulated peripheral blood mononuclear cells from rhesus monkeys immunized with DNA replication-defective adenovirus vector expressing various SIV genes, as an ex vivo model, to mimic the effects of different immune effector functions on viral infection.

Results: VVR was attenuated by the immunization and correlated 2 weeks after first boost, with the number of interferon gamma-secreting cells and T-cell noncytotoxic antiviral responses. Importantly, VVR on the day of challenge but not interferon gamma responses correlated with viremia and with memory CD4+ T-cell measurements after SIVmac239 challenge. Similarly, T-cell noncytotoxic antiviral responses on the day of challenge correlated directly with memory CD4+ T cell and inversely with plasma viremia after challenge.

Conclusions: VVR thus served as a better predictor of protective capacity of the vaccine regimen in these monkeys. We suggest that VVR be considered in the evaluation of candidate AIDS vaccines in humans.

From the *Department of Virology and Immunology, German Primate Centre, Kellnerweg, Goettingen, Germany; and †Cellular Immunology Laboratory, Division of Molecular and Life Sciences, Pohang University of Science and Technology, Republic of Korea. Dr. Washingtone Ochieng, PhD, is presently with the Division of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.

Received for publication March 18, 2009; accepted June 8,2009.

Supported by grants from the POSTECH Biotech Centre, the KOSEF (Korea government; M10534050001-06N3405-00110), the Genexine Co Ltd, Dr. Sung's Laboratory and the German Primate Centre. Personnel support to W. Ochieng′ was provided by the German Academic Exchange Services (DAAD).

Presented in parts at the International Meeting of The Institute of Human Virology, November 17-21, 2006, Baltimore, MD, in Retrovirology. 2006;3(Suppl 1):46; at the XVI International AIDS Conference, August 13-18, 2006, Toronto, Canada. Abstract WEAA0204; and at the Cold Spring Habor meeting on retroviruses, May 22-27, 2007, New York, NY.

The authors of the study declare no conflict of interest.

Correspondence to: Dr. Sieghart Sopper, PhD, Department of Infection Biology, German Primate Centre, Kellnerweg 4, 37077, Goettingen, Germany (e-mail: sopper@dpz.eu).

© 2009 Lippincott Williams & Wilkins, Inc.