Title:B-Cells and the Use of Non-Human Primates for Evaluation of HIV Vaccine Candidates
Volume: 13
Issue: 6
Author(s): Thorsten Demberg and Marjorie Robert-Guroff
Affiliation:
Keywords:
B cell development, B cell dysfunction, B cell maturation, HIV, non-human primate model, SIV, vaccine
development.
Abstract: The RV144 clinical trial in Thailand associated vaccine-induced antibodies with protective efficacy, leading to
a focus in HIV vaccine research on protective antibody induction. This has necessitated greater understanding of B cell
biology in humans as well as non-human primates (NHP), the principle animal model for pre-clinical HIV/SIV vaccine
research. This review covers development and maturation of NHP B cells within the framework of current knowledge of
human and murine B cells. Identification of many NHP B cell subpopulations is now possible, although consensus is
lacking in some cases, and better distinction of some populations is still needed. Elucidation of mechanisms that control
germinal center maintenance, selection of B cells into the memory cell pool, and differentiation of B cells into long-lived
plasma cells remains critical for improving vaccine design. B cell dysfunction occurs during both HIV and SIV infection.
Whether the processes leading to this impairment are identical in humans and NHP is not known. Uncovering the
mechanisms involved could lead to improved treatment regimens. The SIV/NHP model effectively mimics HIV infection
of people, but key differences between NHP and humans in antibody characteristics such as glycosylation and structure
may lead to unexpected outcomes in pre-clinical studies. Important new areas for investigation include the role of B cell
cytokines in the immune system and the impact of the microbiome on B cell development and maturation. Enhanced
knowledge of B cells in NHP as well as humans should enable improved vaccine design, leading to induction of potent,
long-lasting protective antibodies.