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

doi:10.1016/j.celrep.2023.113450

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

Cell Rep. 2023 Dec 26;42(12):113450. doi: 10.1016/j.celrep.2023.113450. Epub 2023 Nov 28.

Authors

Flavio Matassoli¹, Alberto Cagigi², Chen-Hsiang Shen², Amy R Henry², Timothy S Johnston², Chaim A Schramm², Christopher A Cottrell³, Oleksandr Kalyuzhniy³, Abby Spangler², Leigh Eller⁴, Merlin Robb⁴, Michael Eller⁵, Prossy Naluyima⁶, Peter D Kwong⁷, Daniel C Douek², William R Schief³, Sarah F Andrews⁸, Adrian B McDermott²

Affiliations

¹ Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. Electronic address: flavio.matassoli@nih.gov.
² Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
³ Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA, USA.
⁴ U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA; Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
⁵ U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
⁶ Makerere University Walter Reed Project, Kampala, Uganda.
⁷ Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY, USA.
⁸ Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. Electronic address: sarah.andrews2@nih.gov.

Abstract

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.

Keywords: B cell; CP: Immunology; CP: Microbiology; HIV; vaccine.

MeSH terms

Antibodies, Neutralizing
HIV Antibodies
HIV Envelope Protein gp120
HIV Infections*
HIV-1*
Humans
Precursor Cells, B-Lymphoid

Substances

Antibodies, Neutralizing
HIV Antibodies
HIV Envelope Protein gp120

Grants and funding

ZIA AI005143/ImNIH/Intramural NIH HHS/United States