A human monoclonal antibody blocks malaria transmission and defines a highly conserved neutralizing epitope on gametes.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 33741942.
- Also identified by DOI 10.1038/s41467-021-21955-1 and PMC identifier 7979743.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Malaria elimination requires tools that interrupt parasite transmission. Here, we characterize B cell receptor responses among Malian adults vaccinated against the first domain of the cysteine-rich 230 kDa gamete surface protein Pfs230, a key protein in sexual stage development of P. falciparum parasites. Among nine Pfs230 human monoclonal antibodies (mAbs) that we generated, one potently blocks transmission to mosquitoes in a complement-dependent manner and reacts to the gamete surface; the other eight show only low or no blocking activity. The structure of the transmission-blocking mAb in complex with vaccine antigen reveals a large discontinuous conformational epitope, specific to domain 1 of Pfs230 and comprising six structural elements in the protein. The epitope is conserved, suggesting the transmission-blocking mAb is broadly functional. This study provides a rational basis to improve malaria vaccines and develop therapeutic antibodies for malaria elimination.
Medical subject headings
- Antibodies, Monoclonal
- Antibodies, Protozoan
- Epitopes
- Germ Cells
- Malaria, Falciparum
- Plasmodium falciparum