The purpose of the present review is to provide an update on the current development in the field of broadly neutralizing antibodies (bNabs) and their potential use in the prevention and therapeutic settings, and an evaluation of the B-cell abnormalities that may impair antibody responses in HIV infection.
Major advances have been achieved in the characterization of bNabs directed against different vulnerable regions of HIV Envelope (Env). Recent observations have clearly demonstrated the ability of bNabs to prevent HIV infection in the nonhuman primate model of HIV infection and to suppress viremia in individuals with chronic HIV infection in the absence of antiretroviral therapy. Furthermore, substantial advances have also been obtained in the development of HIV Env proteins and immunization strategies inducing bNabs in small animal models. Several studies have also shed light on the B-cell abnormalities associated with the viremic phase of HIV infection that cause impaired B-cell maturation and antibody responses. Of note, preliminary observations have provided evidence for a correlation between the expansion of a specific population of B cells, for example, germinal center B cells, the expansion of T follicular helper cells (Tfh), and the generation of neutralizing antibodies.
The recent observations on the antiviral effects of bNabs in vivo indicate that bNabs may play a central role in both the prevention and the therapeutic settings. The identification of the role of germinal center B cells and Tfh cells as critical components of the immune response leading to the generation of neutralizing antibodies, will allow the development of specific immunization strategies for the stimulation of germinal center B cells and Tfh cells. A lot of work still remains to be done for the delineation of B-cell and Tfh cell biology from human lymphoid tissues and in the development of HIV Env proteins and immunization strategies leading to the generation of bNabs.