A new study published in the Nature Communications has revealed that the data indicate that possession of antibody responses to a group of Pfalciparum proteins increases the likelihood of antibody-mediated transmission inhibition.

Plasmodium gametocytes develop from their asexual progenitors and are the only malaria parasite life-stage infective to mosquitoes. In preparation for their development in the mosquito, gametocytes cease to express many proteins involved in the parasites cycle of asexual replication and upregulate others that are involved in sexual development.

Some of these have essential roles in mosquito-stage development, which culminates in the insect becoming infectious to humans. In surveys where mosquitoes were fed directly on the skin or on a blood sample, it was noted that some gametocytaemic individuals including those with high gametocyte densities were not infectious.

Infection with Plasmodium can elicit antibodies that inhibit parasite survival in the mosquito when they are ingested in an infectious blood meal. In the present study, researchers 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.

The research team 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.

The analysis demonstrates that host antibody responses to gametocyte proteins are associated with reduced malaria transmission efficiency from humans to mosquitoes. Whilst further studies are needed to assess the generalizability of this signature of TRA across endemic settings, the strong association of the SMFA-based signature of TRA with reduced transmission potential during natural infections is very promising. Future studies should aim to assess the kinetics of antibody responses to these antigens and their association with TRA using longitudinal cohorts, with well-defined clinical, parasitological and infectivity data.