Cell Reports (Dec 2023)

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

  • Flavio Matassoli,
  • Alberto Cagigi,
  • Chen-Hsiang Shen,
  • Amy R. Henry,
  • Timothy S. Johnston,
  • Chaim A. Schramm,
  • Christopher A. Cottrell,
  • Oleksandr Kalyuzhniy,
  • Abby Spangler,
  • Leigh Eller,
  • Merlin Robb,
  • Michael Eller,
  • Prossy Naluyima,
  • Peter D. Kwong,
  • Daniel C. Douek,
  • William R. Schief,
  • Sarah F. Andrews,
  • Adrian B. McDermott

Journal volume & issue
Vol. 42, no. 12
p. 113450

Abstract

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Summary: 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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