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Immunity. 2019 Mar 19;50(3):677-691.e13. doi: 10.1016/j.immuni.2019.02.008. Epub 2019 Mar 12.

Longitudinal Analysis Reveals Early Development of Three MPER-Directed Neutralizing Antibody Lineages from an HIV-1-Infected Individual.

Author information

1
U.S. Military HIV Research Program, WRAIR, Silver Spring, MD, USA; Henry Jackson Foundation, Bethesda, MD, USA.
2
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
3
Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN, USA.
4
Department of Chemical Engineering, University of Texas at Austin, Austin, TX, USA.
5
Duke University School of Medicine and Center for HIV/AIDS Vaccine Immunology - Immunogen Discovery, Durham, NC, USA.
6
Electron Microscopy Laboratory, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA.
7
U.S. Military HIV Research Program, WRAIR, Silver Spring, MD, USA.
8
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA; Columbia University, New York, NY, USA.
9
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA; Columbia University, New York, NY, USA. Electronic address: pdkwong@nih.gov.
10
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. Electronic address: nicole.doriarose@nih.gov.

Abstract

Lineage-based vaccine design is an attractive approach for eliciting broadly neutralizing antibodies (bNAbs) against HIV-1. However, most bNAb lineages studied to date have features indicative of unusual recombination and/or development. From an individual in the prospective RV217 cohort, we identified three lineages of bNAbs targeting the membrane-proximal external region (MPER) of the HIV-1 envelope. Antibodies RV217-VRC42.01, -VRC43.01, and -VRC46.01 used distinct modes of recognition and neutralized 96%, 62%, and 30%, respectively, of a 208-strain virus panel. All three lineages had modest levels of somatic hypermutation and normal antibody-loop lengths and were initiated by the founder virus MPER. The broadest lineage, VRC42, was similar to the known bNAb 4E10. A multimeric immunogen based on the founder MPER activated B cells bearing the unmutated common ancestor of VRC42, with modest maturation of early VRC42 intermediates imparting neutralization breadth. These features suggest that VRC42 may be a promising template for lineage-based vaccine design.

KEYWORDS:

HIV envelope; neutralizing antibody; next-generation sequencing

PMID:
30876875
PMCID:
PMC6555550
[Available on 2020-03-19]
DOI:
10.1016/j.immuni.2019.02.008

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