Comparative efficacy of subtype AE simian-human immunodeficiency virus priming and boosting vaccines in pigtail macaques

被引:46
作者
De Rose, Robert
Batten, C. Jane
Smith, Miranda Z.
Fernandez, Caroline S.
Peut, Viv
Thomson, Scott
Ramshaw, Ian A.
Coupar, Barbara E. H.
Boyle, David B.
Venturi, Vanessa
Davenport, Miles P.
Kent, Stephen J. [1 ]
机构
[1] Univ Melbourne, Dept Microbiol & Immunol, Melbourne, Vic 3010, Australia
[2] Australian Natl Univ, John Curtin Sch Med Res, Canberra, ACT 2601, Australia
[3] CSIRO, Geelong, Vic 3220, Australia
[4] Univ New S Wales, Ctr Vasc Res, Kensington, NSW 2052, Australia
关键词
D O I
10.1128/JVI.01727-06
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Vaccination against AIDS is hampered by great diversity between human immunodeficiency virus (HfV) 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. SIN 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 SHIN vaccination. Peak viral load was modestly (0.4 log(10) 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.
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页码:292 / 300
页数:9
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