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
Affiliations
Flavio Matassoli
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA; Corresponding author
Alberto Cagigi
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
Chen-Hsiang Shen
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
Amy R. Henry
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
Timothy S. Johnston
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
Chaim A. Schramm
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
Christopher A. Cottrell
Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA, USA
Oleksandr Kalyuzhniy
Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA, USA
Abby Spangler
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
Leigh Eller
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
Merlin Robb
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
Michael Eller
U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA
Prossy Naluyima
Makerere University Walter Reed Project, Kampala, Uganda
Peter D. Kwong
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
Daniel C. Douek
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
William R. Schief
Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA, USA
Sarah F. Andrews
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA; Corresponding author
Adrian B. McDermott
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
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.
