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Correspondence Author: Dr. Rama Rao Amara Phone: (404) 727-8765; Fax: (404) 727-7768; 954 Gatewood Rd, Atlanta, GA 30329, USA ramara@emory.edu

Current address for H.L.R.: Geovax Inc., Atlanta GA, 30306 USA

S.K., P.N., and V.V. contributed equally to this work

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Research Funding:

This work was supported by the National Institutes of Health/National Institute of Allergy and Infectious Diseases grants R01 AI057029 and R01 AI071852 to RRA; Yerkes National Primate Research Center base grant, P51 RR00165; Emory CFAR grant P30 AI050409; and R24 RR16038 to David I. Watkins.

Preexisting Vaccinia Virus Immunity Decreases SIV-Specific Cellular Immunity but does not diminish Humoral Immunity and Efficacy of a DNA/MVA Vaccine

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Journal Title:

Journal of Immunology

Volume:

Volume 185, Number 12

Publisher:

, Pages 7262-7273

Type of Work:

Article | Post-print: After Peer Review

Abstract:

The influence of preexisting immunity to viral vectors is a major issue for the development of viral vectored vaccines. Here, we investigate the effect of preexisting vaccinia virus immunity on the immunogenicity and efficacy of a DNA/MVA SIV vaccine in rhesus macaques using a pathogenic intrarectal SIV251 challenge. Preexisting immunity decreased SIV-specific CD8 and CD4 T cell responses, but preserved the SIV-specific humoral immunity. In addition, preexisting immunity did not diminish the control of a SIV challenge mediated by the DNA/MVA vaccine. The peak and set point viremia was 150- and 17-fold lower, respectively in preimmune animals compared to control animals. The peak and set point viremia correlated directly with colorectal virus at 2 weeks post challenge suggesting that early control of virus replication at the site of viral challenge was critical for viral control. Factors that correlated with early colorectal viral control included (i) the presence of anti-SIV IgA in rectal secretions, (ii) high avidity binding antibody for the native form of Env and (iii) low magnitude of vaccine-elicited SIV-specific CD4 T cells displaying the CCR5 viral co-receptor. The frequency of SIV-specific CD8 T cells in blood and colorectal tissue at 2 weeks post challenge did not correlate with early colorectal viral control. These results suggest that preexisting vaccinia virus immunity may not limit the potential of recombinant MVA vaccines to elicit humoral immunity and highlight the importance of immunodeficiency virus vaccines achieving early control at the mucosal sites of challenge.

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The Journal of Immunology. All rights reserved.

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