Memory and CAR-NK cell-based novel approaches for HIV vaccination and eradication.

ABSTRACT

Human immunodeficiency virus (HIV) is one of the critical infectious agents with thousands of newly infected people worldwide. High mutational capability and rapid diversification, inhibition of humoral and cellular immune responses, and thus inability for recognition of an immunogenic region in the viral envelope by the immune system are major challenges. Natural killer (NK) cells are multifunctional, playing a key role in the identification and elimination of HIV-infected cells. These cells identify and eliminate virus-infected cells in a multilateral manner, such as ligand stress, antibody-dependent cell cytotoxicity (ADCC), T follicular helper (Tfh), and the activation of most of the stimulatory receptors. Moreover, these cells release cytokines leading to the activation of cytotoxic lymphocytes (CTLs) and dendritic cells (DCs), contributing to efficient viral elimination. Some subsets of NK cells exhibit putatively enhanced effector functions against viruses following vaccination easily expanded and identified by NK cell lines culture. Furthermore, NK cells promote the elimination of HIV-infected cells which reduce the expression of major histocompatibility complex (MHC) molecules. Memory NK cells have higher functionality and renewable potential. A pioneering strategy to establish an efficacious HIV vaccine would include stimulation of the accumulation and long-term maintenance of these HIV-reactive NK cells. CAR-NK (chimeric antigen receptor-natural killer) cells-based antiviral therapies have emerged as novel approaches with the ability of antigen recognition and more advantages than CAR-T (chimeric antigen receptor-T) cells. Recent development of induced pluripotent stem cell (iPSC)-derived NK cells with enhanced activity and efficiency conferred a promising insight into CAR-NK cell-based therapies. Therefore, memory and CAR-NK cells-based approaches can emerge as novel strategies providing implications for HIV vaccine design and therapy.