Natural Malaria Infection Elicits Rare But Potent Neutralizing Antibodies To The Bloodstage Antigen Rh5 Lawrence T Wang by Lawrence T. Wang, Andrew J.r. Cooper, instant download after payment.

SUMMARYPlasmodium 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 studythe 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 immunoglobulinG (IgG) responses to RH5 were short-lived in malaria-exposed Malian individuals, despite repeated infectionsover multiple years. RH5-specific monoclonal antibodies isolated from eight malaria-exposed individualsmostly 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 Malianindividuals, were among the most potent neutralizers out of 186 antibodies from both cohorts and targetedthe same epitopes as the most potent vaccine-induced antibodies. These results suggest that natural malariainfection may boost RH5-vaccine-induced responses and provide a clear strategy for the development ofnext-generation RH5 vaccines.