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Review
. 2015 Aug:35:1-8.
doi: 10.1016/j.coi.2015.05.001. Epub 2015 May 18.

HIV therapeutic vaccines: moving towards a functional cure

Geetha H Mylvaganam  1 , Guido Silvestri  2 , Rama Rao Amara  3
Affiliations
Review

HIV therapeutic vaccines: moving towards a functional cure

Geetha H Mylvaganam et al. Curr Opin Immunol. 2015 Aug.

Abstract

Anti-viral T-cell and B-cell responses play a crucial role in suppressing HIV and SIV replication during chronic infection. However, these infections are rarely controlled by the host immune response, and most infected individuals need lifelong antiretroviral therapy (ART). Recent advances in our understanding of how anti-HIV immune responses are elicited and regulated prompted a surge of interest in harnessing these responses to reduce the HIV 'residual disease' that is present in ART-treated HIV-infected individuals. Novel approaches that are currently explored include both conventional therapeutic vaccines (i.e., active immunization strategies using HIV-derived immunogens) as well as the use of checkpoint blockers such as anti-PD-1 antibodies. These approaches appear promising as key components of complex therapeutic strategies aimed at curing HIV infection.

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Figures

Figure 1
Figure 1
Potential mechanisms of viral control by therapeutic vaccines. ART therapy has allowed for profound control of viral replication in HIV infected individuals, but is able to only partially restore immune function. Multiple arms of the immune response are compromised during chronic HIV infection and remain less functional under highly suppressive ART including; impaired innate responses, exhausted anti-viral CD8 T cell responses, and productive infection of CD4 T cells including Tfh cells, restricted mainly to the germinal centers of B cell follicles that are largely devoid of anti-viral CD8 T cells. Therapeutic vaccinations in combination with other immune based therapies have the potential to beneficially modulate multiple immune parameters that are crucial for long term control of viremia in the absence of ART and these include improving the function of professional APCs, expansion of highly functional CD8 T cells with broad specificity and the ability to infiltrate into sites of latent viral replication such as B cell follicles, restoration of mucosal homeostasis to diminish hyperimmune activation, and the induction of functional antibody response. These interventions may lead to a decrease in persistent viral reservoirs that may result in delayed viral resurgence and a significant reduction in viral set-point post ART interruption, facilitating host control of HIV. Keywords: APC, antigen presenting cells; Tfh, T follicular helper cells; Nab, neutralizing antibodies, nNAb, non-neutralizing antibodies.
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