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Journal of Virology, January 2007, p. 292-300, Vol. 81, No. 1
0022-538X/07/$08.00+0     doi:10.1128/JVI.01727-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Comparative Efficacy of Subtype AE Simian-Human Immunodeficiency Virus Priming and Boosting Vaccines in Pigtail Macaques

Robert De Rose,^1, C. Jane Batten,^1, Miranda Z. Smith,¹ Caroline S. Fernandez,¹ Viv Peut,¹ Scott Thomson,² Ian A. Ramshaw,² Barbara E. H. Coupar,³ David B. Boyle,³ Vanessa Venturi,⁴ Miles P. Davenport,⁴ and Stephen J. Kent^1*

Department of Microbiology and Immunology, University of Melbourne, Victoria 3010, Australia,¹ John Curtin School of Medical Research, Australian National University, Canberra ACT 2601, Australia,² CSIRO Livestock Industries, Geelong Victoria 3220, Australia,³ Centre for Vascular Research, University of NSW, Kensington NSW 2052, Australia⁴

Received 9 August 2006/ Accepted 9 October 2006

Vaccination against AIDS is hampered by great diversity between human immunodeficiency virus (HIV) strains. Heterologous B-subtype-based simian-human immunodeficiency virus (SHIV) DNA prime and poxvirus boost vaccine regimens can induce partial, T-cell-mediated, protective immunity in macaques. We analyzed a set of DNA, recombinant fowlpox viruses (FPV), and vaccinia viruses (VV) expressing subtype AE HIV type 1 (HIV-1) Tat, Rev, and Env proteins and SIV Gag/Pol in 30 pigtail macaques. SIV Gag-specific CD4 and CD8 T-cell responses were induced by sequential DNA/FPV vaccination, although lower FPV doses, VV/FPV vaccination, and DNA vaccines alone were not as consistently immunogenic. The SHIV AE DNA prime, FPV boost regimens were significantly less immunogenic than comparable B-subtype SHIV vaccination. Peak viral load was modestly (0.4 log₁₀ copies/ml) lower among the AE subtype SHIV-immunized animals compared to controls following the virulent B subtype SHIV challenge. Protection from persistent high levels of viremia and CD4 T-cell depletion was less in AE subtype compared to B subtype SHIV-vaccinated macaques. Gag was highly immunodominant over the other AE subtype SHIV vaccine proteins after vaccination, and this immunodominance was exacerbated after challenge. Interestingly, the lower level of priming of immune responses did not blunt postchallenge Gag-specific recall responses, despite more modest protection. These studies suggest priming of T-cell immunity to prevent AIDS in humans is possible, but differences in the immunogenicity of various subtype vaccines and broad cross-subtype protection are substantial hurdles.

Published ahead of print on 18 October 2006.

R.D. and C.J.B. contributed equally to the work.

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