Abstract
We discuss here some of the key immunological elements that are at the crossroads and need to be combined to develop a potent therapeutic HIV-1 vaccine. Therapeutic vaccines have been commonly used to enhance and/or recall pre-existing HIV-1-specific cell-mediated immune responses aiming to suppress virus replication. The current success of immune checkpoint blockers in cancer therapy renders them very attractive to use in HIV-1 infected individuals with the objective to preserve the function of HIV-1-specific T cells from exhaustion and presumably target the persistent cellular reservoir. The major latest advances in our understanding of the mechanisms responsible for virus reactivation during therapy-suppressed individuals provide the scientific basis for future combinatorial therapeutic vaccine development.
Highlights
After almost forty years of HIV-1 infection, we have not been able to achieve a cure, and none of the vaccines have proven to be effective
Some novel immuno-cytokines with improved half-life and physicochemical properties, such as IL-15 superagonists, have proven their potency. This will hopefully guide new avenues for developing combinatorial therapeutic vaccines with the objective to preserve the function of HIV-specific T cells from exhaustion and reduce the HIV-1 reservoir
We have reported that CD4+ Tregs express a reduced expression of IL-7Ra chain [5] but an increased expression of IL-2Ra chain [6], and this is very interesting because these two important molecules can be simultaneously targeted to potentiate effector T cells in therapeutic HIV-1 vaccination
Summary
After almost forty years of HIV-1 infection, we have not been able to achieve a cure, and none of the vaccines have proven to be effective (reviewed in [1]). The field has established solid platforms for basic immunology, pathophysiology, and development of new immunomodulatory agents that have proven their efficacy in animal models and in vitro experiments. A new vaccine concept with the idea of mobilizing the immune system is the way to go, in order to reverse the persistent inflammation and rescue anti-HIV-1 T-cell responses that enable the clearance of the reservoir. Some immunological interventions using novel immune-cytokines, immune checkpoint blockers, and/or latency reversing agents are warranted. Some novel immuno-cytokines with improved half-life and physicochemical properties, such as IL-15 superagonists, have proven their potency. This will hopefully guide new avenues for developing combinatorial therapeutic vaccines with the objective to preserve the function of HIV-specific T cells from exhaustion and reduce the HIV-1 reservoir.
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