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

• Published in: Cell reports (Cambridge) 2023-12, Vol.42 (12), p.113450-113450, Article 113450
• Main Authors: Matassoli, Flavio, Cagigi, Alberto, Shen, Chen-Hsiang, Henry, Amy R., Johnston, Timothy S., Schramm, Chaim A., Cottrell, Christopher A., Kalyuzhniy, Oleksandr, Spangler, Abby, Ndung'u, Thumbi, Dong, Krista, Eller, Leigh, Robb, Merlin, Eller, Michael, Naluyima, Prossy, Kwong, Peter D., Douek, Daniel C., Schief, William R., Andrews, Sarah F., McDermott, Adrian B.
• Format: Article
• Language: English
• Subjects: Antibodies, Neutralizing; B cell; CP: Immunology; CP: Microbiology; HIV; HIV Antibodies; HIV Envelope Protein gp120; HIV Infections; HIV-1; Humans; Precursor Cells, B-Lymphoid; vaccine
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2023.113450

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. [Display omitted] •Sub-Saharan African cohorts have high frequencies of eOD-GT8-specific naive B cells•eOD-GT8-specific naive B cells in this cohort express VRC01-class antibody precursor genes•IOMA, VRC23, and VRC16 HIV CD4bs-specific antibody signatures are also detected Germline-targeting HIV vaccine strategies depend on the frequency of vaccine-specific naive B cell precursors. Matassoli et al. show that the frequency and immunoglobulin signature of B cells binding the immunogen eOD-GT8 in sub-Saharan African cohorts are higher or equivalent to those of a U.S. cohort, suggesting that it could prove effective in Africa.