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

Purpose of review 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. Recent findings 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. Summary 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.