Natural malaria infection elicits rare but potent neutralizing antibodies to the blood-stage antigen RH5

被引：7

作者：

Wang, Lawrence T. ^{[1
,2
,3
,4
,5
]}

Cooper, Andrew J. R. ^{[1
]}

Farrell, Brendan ^{[3
,5
]}

Miura, Kazutoyo ^{[6
]}

Diouf, Ababacar ^{[6
]}

Muller-Sienerth, Nicole ^{[7
]}

Crosnier, Cecile ^{[8
]}

Purser, Lauren ^{[1
,16
]}

Kirtley, Payton J. ^{[9
]}

Maciuszek, Maciej ^{[3
]}

Barrett, Jordan R. ^{[3
,5
,17
]}

McHugh, Kirsty ^{[3
,5
]}

Ogwang, Rodney ^{[2
]}

Tucker, Courtney ^{[1
]}

Li, Shanping ^{[10
]}

Doumbo, Safiatou ^{[11
]}

Doumtabe, Didier ^{[11
]}

Pyo, Chul-Woo

Skinner, Jeff ^{[10
]}

Nielsen, Carolyn M. ^{[3
,5
]}

Silk, Sarah E. ^{[3
,5
]}

Kayentao, Kassoum ^{[11
]}

Ongoiba, Aissata ^{[11
]}

Zhao, Ming ^{[13
]}

Nguyen, Doan C. ^{[14
]}

Lee, F. Eun-Hyung ^{[14
]}

Minassian, Angela M. ^{[3
,5
,15
]}

Geraghty, Daniel E. ^{[12
]}

Traore, Boubacar ^{[11
]}

Seder, Robert A. ^{[2
]}

Wilder, Brandon K. ^{[9
]}

Crompton, Peter D. ^{[10
]}

Wright, Gavin J.

Long, Carole A.

Draper, Simon J. ^{[3
,5
,15
]}

Higgins, Matthew K. ^{[3
,5
]}

Tan, Joshua ^{[1
]}

机构：

[1] NIH, NIAID, Lab Immunogenet, Antibody Biol Unit, Rockville, MD 20852 USA

[2] NIH, NIAID, Vaccine Res Ctr, Bethesda, MD 20892 USA

[3] Univ Oxford, Dept Biochem, South Parks Rd, Oxford OX1 3QU, England

[4] Univ Calif San Diego, Sch Med, Med Scientist Training Program, La Jolla, CA 92093 USA

[5] Univ Oxford, Kavli Inst Nanosci Discovery, Dorothy Crowfoot Hodgkin Bldg,South Parks Rd, Oxford OX1 3QU, England

[6] NIH, NIAID, Lab Malaria & Vector Res, Rockville, MD USA

[7] Wellcome Sanger Inst, Cambridge CB10 1SA, England

[8] Univ York, Hull York Med Sch, York Biomed Res Inst, Dept Biol, York YO10 5DD, England

[9] Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Portland, OR 97006 USA

[10] NIH, NIAID, Malaria Infect Biol & Immun Sect, Lab Immunogenet, Rockville, MD 20852 USA

[11] Univ Sci Tech & Technol Bamako, Mali Int Ctr Excellence Res, Point G,BP 1805, Bamako, Mali

[12] Fred Hutchinson Canc Res Ctr, Clin Res Div, Seattle, WA 98109 USA

[13] NIH, NIAID, Prot Chem Sect, Res Technol Branch, Rockville, MD USA

[14] Emory Univ, Div Pulm Allergy Crit Care & Sleep Med, Atlanta, GA 30322 USA

[15] NIHR Oxford Biomed Res Ctr, Oxford OX3 9DU, England

[16] MilliporeSigma, 400 Summit Dr, Burlington, MA 01803 USA

[17] Scripps Res, Dept Integrat Struct & Computat Biol, La Jolla, CA 92037 USA

来源：

CELL | 2024年 / 187卷 / 18期

基金：

美国国家卫生研究院; 英国惠康基金;

关键词：

Highlights; specific B cells; HUMAN MONOCLONAL-ANTIBODIES; VACCINE; INVASION; TARGETS; BASIGIN; GROWTH;

D O I：

10.1016/j.cell.2024.06.037

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Plasmodium falciparum reticulocyte-binding protein homolog 5 (RH5) is the most advanced blood-stage malaria vaccine candidate and is being evaluated for efficacy in endemic regions, emphasizing the need to study the underlying antibody response to RH5 during natural infection, which could augment or counteract responses to vaccination. Here, we found that RH5-reactive B cells were rare, and circulating immunoglobulin G (IgG) responses to RH5 were short-lived in malaria-exposed Malian individuals, despite repeated infections over multiple years. RH5-specific monoclonal antibodies isolated from eight malaria-exposed individuals mostly targeted non-neutralizing epitopes, in contrast to antibodies isolated from five RH5-vaccinated, malaria-naive UK individuals. However, MAD8-151 and MAD8-502, isolated from two malaria-exposed Malian individuals, were among the most potent neutralizers out of 186 antibodies from both cohorts and targeted the same epitopes as the most potent vaccine-induced antibodies. These results suggest that natural malaria infection may boost RH5-vaccine-induced responses and provide a clear strategy for the development of next-generation RH5 vaccines.

引用

页数：30

共 29 条

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