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Opening Fronts in HIV Vaccine Development: Targeting reservoirs to clear and cure

Nature Medicine volume 20, pages 480–481 (2014)Cite this article

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HIV-1 vaccine development efforts have recently been focused on neutralizing antibodies, with the assumption that it is essential to neutralize free virus particles and prevent the initial infection of host cells. However, once stable reservoirs of infected cells are established, clearing the infection is much more difficult and will probably depend on other immune mechanisms. Recent experimental studies in the simian immunodeficiency virus (SIV) model of HIV-1 infection have provided evidence for immunologic clearance of an established SIV infection by a vaccine-induced T cell response1. The findings showing SIV clearance have important implications for vaccination and also come at a time when there is a resurgence of interest in the possibility of curing HIV-1 infection. Although antiretroviral therapy (ART) can largely or completely arrest viral replication2, the stable latent reservoir of HIV-1 in resting memory CD4+ T cells prevents eradication of the infection with ART alone3, and viremia generally rebounds when treatment is stopped. The renewed optimism about curing HIV-1 infection is due in large part to two remarkable clinical cases in which a cure appears to have been achieved4,5. These recent experimental results and clinical studies shed light on the search for a general cure for HIV-1 infection and support the idea that vaccine-induced T cell responses may actually be more effective than early treatment in preventing the establishment of the latent reservoir.

Picker and his colleagues have previously described a cytomegalovirus (CMV)-based SIV vaccine that induces and maintains high levels of effector memory T cells at diverse tissue sites6. This vaccine confers the ability to control a pathogenic SIV infection upon ∼50% of vaccinated macaques6. The reason that only half of the animals experienced this beneficial effect remains unclear; however, in those animals, the initial burst of viral replication was rapidly suppressed. Thereafter, the animals that controlled infection experienced only occasional 'blips' of detectable viremia, which declined in frequency over time. The efficacy of this vaccine derives in part from its ability to induce effector T cells that recognize multiple diverse epitopes in all the SIV proteins found in the vaccine, sometimes in ways that violate the usual patterns of antigen presentation by major histocompatibility complex molecules7.

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Figure 1: Preventing or eliminating HIV-1 reservoirs to cure infection.

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  1. Robert F. Siliciano is at the Johns Hopkins University School of Medicine and the Howard Hughes Medical Institute, Baltimore, Maryland, USA.,

    Robert F Siliciano

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Correspondence to Robert F Siliciano.

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Siliciano, R. Opening Fronts in HIV Vaccine Development: Targeting reservoirs to clear and cure. Nat Med 20, 480–481 (2014). https://doi.org/10.1038/nm.3550

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