High frequency of HIV precursor-target-specific B cells in sub-Saharan populations.

HIV gp120 engineered outer domain germline-targeting version 8 (eOD-GT8) was designed specifically to engage naive B cell precursors of VRC01-class antibodies. However, the frequency and affinity of naive B cell precursors able to recognize eOD-GT8 have been evaluated only in U.S. populations. HIV infection is disproportionally concentrated in sub-Saharan Africa, so we seek to characterize naive B cells able to recognize eOD-GT8 in sub-Saharan cohorts. We demonstrate that people from sub-Saharan Africa have a higher or equivalent frequency of naive B cells able to engage eOD-GT8 compared with people from the U.S. Genetically, the higher frequency of eOD-GT8-positive cells is accompanied by a higher level of naive B cells with gene signatures characteristic of the VRC01 class, as well as other CD4bs-directed antibodies. Our study demonstrates that vaccination with eOD-GT8 in sub-Saharan Africa could be successful at expanding and establishing a pool of CD4bs-directed memory B cells from naive precursors.

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Copyright © 2023. Published by Elsevier Inc.

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Declaration of interests The authors declare no competing interests. This work was supported by a cooperative agreement (W81XWH-18-2-0040) between the Henry M. Jackson Foundation (HJF) for the Advancement of Military Medicine, Inc., and the U.S. Department of Defense (DOD). This research was funded, in part, by the National Institute of Allergy and Infectious Diseases. The views expressed are those of the authors and should not be construed to represent the positions of the U.S. Army, the DOD, or the HJF. The investigators have adhered to the policies for protection of human subjects as prescribed in AR 70-25.