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Journal of Virology, December 2005, p. 15356-15367, Vol. 79, No. 24
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.24.15356-15367.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

A Combination DNA and Attenuated Simian Immunodeficiency Virus Vaccine Strategy Provides Enhanced Protection from Simian/Human Immunodeficiency Virus-Induced Disease{dagger}

Rama Rao Amara,1,4 Kalpana Patel,1 Genevieve Niedziela,1 Pragati Nigam,4 Sunita Sharma,4 Silvija I. Staprans,4,5 David C. Montefiori,8 Lakshmi Chenareddi,1 James G. Herndon,2 Harriet L. Robinson,1,4,6 Harold M. McClure,3,7 and Francis J. Novembre1,4,6*

Divisions of Microbiology and Immunology,1 Neuroscience,2 Pathology, Yerkes National Primate Research Center,3 Departments of Medicine,5 Microbiology,6 Pathology,7 Vaccine Research Center, Emory University School of Medicine, Atlanta, Georgia 30329,4 Department of Surgery, Laboratory for AIDS Vaccine Research and Development, Duke University Medical Center, Durham, North Carolina8

Received 22 April 2005/ Accepted 15 September 2005

Among the most effective vaccine candidates tested in the simian immunodeficiency virus (SIV)/macaque system, live attenuated viruses have been shown to provide the best protection from challenge. To investigate if preimmunization would increase the level of protection afforded by live attenuated SIVmac239{Delta}nef ({Delta}nef), macaques were given two priming immunizations of DNA encoding SIV Gag and Pol proteins, with control macaques receiving vector DNA immunizations. In macaques receiving the SIV DNA inoculation, SIV-specific cellular but not humoral responses were readily detectable 2 weeks after the second DNA inoculation. Following boosting with live attenuated virus, control of {Delta}nef replication was superior in SIV-DNA-primed macaques versus vector-DNA-primed macaques and was correlated with higher levels of CD8+/gamma-interferon-positive and/or interleukin-2-positive cells. Challenge with an intravenous inoculation of simian/human immunodeficiency virus (SHIV) strain SHIV89.6p resulted in infection of all animals. However, macaques receiving SIV DNA as the priming immunizations had statistically lower viral loads than control animals and did not develop signs of disease, whereas three of seven macaques receiving vector DNA showed severe CD4+ T-cell decline, with development of AIDS in one of these animals. No correlation of immune responses to protection from disease could be derived from our analyses. These results demonstrate that addition of a DNA prime to a live attenuated virus provided better protection from disease following challenge than live attenuated virus alone.

* Corresponding author. Mailing address: Yerkes National Primate Research Center, Emory University, 954 N. Gatewood Rd., Atlanta, GA 30329. Phone: (404) 727-7216. Fax: (404) 727-1488. E-mail: fnovembr{at}rmy.emory.edu.

{dagger} Dedicated to the memory of Harold M. McClure, 2 October 1937 to 23 October 2004.

Journal of Virology, December 2005, p. 15356-15367, Vol. 79, No. 24
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.24.15356-15367.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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