Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

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.

Original publication

DOI

10.1016/j.cell.2024.06.037

Type

Journal article

Journal

Cell

Publication Date

05/09/2024

Volume

187

Pages

4981 - 4995.e14

Keywords

Plasmodium falciparum, RH5, malaria, monoclonal antibodies, natural infection, vaccine design, Humans, Antibodies, Neutralizing, Plasmodium falciparum, Malaria, Falciparum, Malaria Vaccines, Antibodies, Protozoan, Antigens, Protozoan, Immunoglobulin G, Protozoan Proteins, Antibodies, Monoclonal, Adult, B-Lymphocytes, Epitopes, Female, Mali, Carrier Proteins, Male, Adolescent