The role of mosquito saliva in malaria parasite transmission

Malaria is a mosquito-borne disease which in 2021 alone caused 619,000 deaths, mainly by the most virulent species to infect humans – Plasmodium falciparum.

Despite intense efforts, malaria elimination has stalled making it imperative to discover new approaches including intervening at the natural bottleneck in the parasite’s life-cycle, the transmission between humans by Anopheles mosquitoes. Before infecting a person, the parasites are confined to the mosquito’s salivary glands.

During infection parasites mix with mosquito saliva and are inoculated into the host.

Intriguingly, my preliminary data shows that antibodies are elicited in humans against mosquito saliva antigens upon exposure to infected mosquito bites.

Furthermore, recent evidence has shown mosquito saliva proteins can bind malaria parasites and modulate their infectivity.

These tantalizing data combined suggest that mosquito saliva proteins are an untapped resource that can aid malaria elimination. However, these saliva-parasite interactions remain poorly understood, and therefore require attention.

I hypothesize that there are many understudied saliva proteins that are co-delivered with the parasite during transmission and interact with and impact parasite infectivity.

I further hypothesize that parasite uptake and colonization of the mosquito is supported by the mosquito’s own saliva proteins, in particular those that inhibit blood clotting.

I aim to unravel how the parasite takes advantage of mosquito saliva proteins to establish an infection in the human host and achieve transmission to mosquitoes.

To accomplish this, I will: 1) characterize how saliva proteins influence P. falciparum infection; 2) identify P. falciparum interacting partners of saliva proteins; and 3) identify which saliva proteins elicit antibody responses sufficient to interrupt infection.

This work will provide unprecedented insights into host-parasite-vector interactions and their impact on parasite infection, and ultimately help to identify novel targets to interrupt the transmission of this devastating disease.