Infection with Plasmodium can elicit antibodies that inhibit parasite survival in the mosquito, when they are ingested in an infectious blood meal. Here, we determine the transmission-reducing activity (TRA) of naturally acquired antibodies from 648 malaria-exposed individuals using lab-based mosquito-feeding assays. Transmission inhibition is significantly associated with antibody responses to Pfs48/45, Pfs230, and to 43 novel gametocyte proteins assessed by protein microarray. In field-based mosquito-feeding assays the likelihood and rate of mosquito infection are significantly lower for individuals reactive to Pfs48/45, Pfs230 or to combinations of the novel TRA-associated proteins. We also show that naturally acquired purified antibodies against key transmission-blocking epitopes of Pfs48/45 and Pfs230 are mechanistically involved in TRA, whereas sera depleted of these antibodies retain high-level, complement-independent TRA. Our analysis demonstrates that host antibody responses to gametocyte proteins are associated with reduced malaria transmission efficiency from humans to mosquitoes.

Protein microarray serological dataBackground corrected and normalised microarray median florescence intensity data, for all individuals in the study (n=648). Data from IVTT protein targets are presented along with control targets in tab 1 and 2 (n=762). Data from the gametocyte IVTT protein targets only are presented in tab 3 (n=528).Data file.xlsxMetadata for the protein micro-array serological analysisMetadata for the protein microarray serological analysis. Full description of the variables provided is in tab 2 (key).Sample file.xlsx