Research ArticleHIV

Immune and Genetic Correlates of Vaccine Protection Against Mucosal Infection by SIV in Monkeys

Science Translational Medicine  04 May 2011:
Vol. 3, Issue 81, pp. 81ra36
DOI: 10.1126/scitranslmed.3002351

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Unraveling Immune Correlates of Vaccine Protection

Developing an effective vaccine against HIV-1, the virus that causes AIDS, has been a huge challenge that has stymied AIDS researchers for several decades. A key problem for HIV vaccine trials has been the lack of immune correlates that indicate which antibody and T cell responses in the vaccinees correlate directly with a protective effect. The only HIV vaccine trial to date that has shown a protective effect is the RV144 trial carried out in Thailand between 2003 and 2006, with the final results reported in 2009. In this trial of 16,400 Thai volunteers, those vaccinated with a prime-boost HIV vaccine showed a reduction in the rate of infection by HIV-1 of 31% compared to volunteers given a placebo. The protective effect was seen for up to 3 years after the initial vaccination, but the immune correlates of protection by this vaccine are still not known.

In an effort to learn more about possible immune correlates of HIV vaccine protection, Letvin and colleagues used a prime/boost vaccine regimen in monkeys that was similar to that used in the RV144 trial. Monkeys were vaccinated with a plasmid DNA prime/recombinant adenovirus serotype 5 (rAd5) boost vaccine regimen and then were challenged with intrarectal doses of one of two isolates of the simian immunodeficiency virus (SIV) every week for 12 weeks. Although the vaccine had no impact on acquisition of the SIVmac251 isolate (which is tough for the monkey immune system to neutralize), the vaccine provided a 50% reduction in infection with the SIVsmE660 isolate (which more readily undergoes neutralization). The authors then examined a variety of immune responses in the protected vaccinated monkeys including cellular, antibody, and innate immune responses; they also examined whether protective host alleles were present in the protected animals. They found that low levels of neutralizing antibodies and a CD4+ T cell response against the HIV envelope (Env) protein correlated with the protective effect. In addition, monkeys that expressed two TRIM5 alleles that help to restrict SIV replication in host cells were protected by the vaccine, whereas monkeys expressing one TRIM5 allele that is permissive for SIV replication were not. This study begins to unravel the immune and genetic correlates of protection in nonhuman primates and highlights the need to scrutinize these types of correlates in future trials of HIV vaccines in human volunteers.


  • These authors contributed equally to this work.

  • Citation: N. L. Letvin, S. S. Rao, D. C. Montefiori, M. S. Seaman, Y. Sun, S.-Y. Lim, W. W. Yeh, M. Asmal, R. S. Gelman, L. Shen, J. B. Whitney, C. Seoighe, M. Lacerda, S. Keating, P. J. Norris, M. G. Hudgens, P. B. Gilbert, A. P. Buzby, L. V. Mach, J. Zhang, H. Balachandran, G. M. Shaw, S. D. Schmidt, J.-P. Todd, A. Dodson, J. R. Mascola, G. J. Nabel, Immune and Genetic Correlates of Vaccine Protection Against Mucosal Infection by SIV in Monkeys. Sci. Transl. Med. 3, 81ra36 (2011).

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