Therapeutic HIV-1 vaccine: time for immunomodulation and combinatorial strategies.

Abstract

The purpose is to recall some of the key immunological elements that are at the crossroad and need to be combined for developing a potent therapeutic HIV-1 vaccine. Therapeutic vaccines and cytokines have been commonly used to enhance and/or recall preexisting HIV-1 specific cell-mediated immune responses aiming to suppress virus replication. While the vaccine is important to stimulate HIV-1 specific T-cell responses, the cytokine may support the expansion of the stimulated virus-specific T cells. Moreover, the current success of immune checkpoint blockers in cancer therapy render them very attractive to use in HIV-1 infected individuals, with the objective to preserve the function of HIV-specific T cells from exhaustion and target directly HIV-1 cell reservoir. More recently, the development of passive immunotherapy using broad neutralizing HIV antibodies (bNAbs) and their potential capacity to elicit innate or adaptive HIV-cellular responses, beyond their neutralizing activity, offers a new opportunity to improve the efficiency of therapeutic vaccine. These major advances provide the scientific basis for developing potent combinatorial interventions in HIV-1 infected patients. Major advances in our immunological understanding resulting from basic science and clinical trials studies have paved the way and established a solid platform to jump over the stumbling blocks that prevent the field from developing a therapeutic HIV-1 vaccine. It is time for immuno-modulation and combinatorial strategies towards HIV-1 eradication.