Can an immune-regulatory vaccine prevent HIV infection?

Abstract

Developing vaccines to prevent the establishment of HIV infection has been fraught with difficulties. It might therefore be important to consider other new strategies. Since several studies suggest that anti-inflammatory stimuli can protect from HIV infection and because HIV replicates preferably in activated T cells, we suggest here that the reduction of immune activation through a HIV-specific regulatory T-cell vaccine might thwart early viral replication. Thus, because immune activation is a good predictor of disease progression and the immune activation set point has been shown to be an early event during HIV infection, vaccinating to achieve control of early virus-specific immune activation might be advantageous.

Figure 1. The two faces of CD4 T-cell activation in HIV infection

While antiviral immunity by CD4 T cells could help to eradicate the virus by providing T-cell help and through direct effects (A), the activated CD4 T cells are more susceptible to becoming infected and thus, providing an optimal environment for HIV replication (B). TCR: T-cell receptor.

Figure 2. Possible way to induce a tolerogenic or regulatory antiviral response

The goal would be to induce a distinct HIV-specific cell type with regulatory properties. DNA vaccination and peptide vaccination that induce a regulatory response but also cell-transfer studies with regulatory DCs and type 1 regulatory T-helper cells have been proven successful in animal models for autoimmune diseases or graft-versus-host diseases. Naive DCs are thought to develop into rDCs upon contact with the regulatory vaccine. In the lymphatic tissue, these rDCs present the antigen in a tolergonic fashion to CD4 and CD8 T cells. Those T cells then acquire a regulatory phenotype. In HIV infection, such cells might be able to prevent activation of HIV target cells, for example, in an IL-10-dependent fashion, which could prevent the establishment of productive infection. DC: Dendritic cell; IDO: Indoleamine 2,3-dioxygenase; PEG: Polyethylene glycol; rDC: Regulatory dendritic cell. Data from [–54,61].