Exposure to the saliva of biting insects could later protect people against infection by insect-borne parasites. If the components of saliva that confer protection can be isolated, they could be used to boost the strength of future vaccines against malaria and other deadly diseases.

The phenomenon has previously been documented in leishmaniasis – a skin disease spread by sandflies that currently afflicts many soldiers returning from Iraq. Now a study in mice has shown mosquito saliva can protect against malaria.

People who live in regions where insect-borne parasitic diseases are widespread, such as Africa and the Middle East, often show greater resistance to infection than people from other parts of the world. It had been assumed that the protection comes from repeated exposure to the parasite over a person’s lifetime, but now it seems that repeated exposure to uninfected saliva could also play a part in generating immunity.

“In some areas people can get up to a thousand mosquito bites a day,” says Mary Ann McDowell, an immunoparasitologist at the University of Notre Dame in Indiana. “That’s a lot of mosquito spit.”


After animal studies showed that prior exposure to sandfly saliva conferred protection against leishmaniasis, McDowell decided to test for the same effect in malaria. Working with researchers at the National Institute of Allergy and Infectious Diseases (NIAID) in Bethesda, Maryland, her team exposed mice to mosquitoes carrying the malaria parasite, some of which had previously been bitten by uninfected mosquitoes.

Mice that were pre-exposed to plain saliva in this way had lower amounts of parasite in their liver and blood. The saliva stimulated their immune systems to produce infection-fighting chemicals called cytokines, which are generally associated with immune cells called T-helper 1 (TH1) cells (Infection and Immunity, DOI: 10.1128/IAI.01928-06). More research is needed before components of insect saliva find their way into a malaria vaccine for humans, says McDowell. Her team is now searching for the specific salivary protein responsible for shifting the immune system to a TH1 response. They then will test whether the same protein exerts a similar protective effect in people.

Mice that were pre-exposed to mosquito saliva had lower amounts of the malaria parasite in their liver and blood

Progress is already being made on vaccines for leishmaniasis. The proteins in sandfly spit that stimulate the TH1 response have already been identified, says Jesus Valenzuela, a biochemist at NIAID who studies leishmaniasis. The proteins are currently being tested for their protective abilities in dogs and monkeys. “We’re trying to mimic what’s happening in nature, to stimulate the same kind of immunity,” says Valenzuela.

Several studies have shown a correlation in humans between exposure to sandfly saliva and resistance to leishmaniasis. Valenzuela has shown that children in Brazil who are naturally resistant to leishmaniasis had a strong immune response to sandfly saliva, while those who contracted the disease showed no such response, indicating they had had no previous exposure to saliva. McDowell’s preliminary results from soldiers returning from Iraq show that those who reported being bitten by flies but did not have leishmaniasis produced more protective TH1 cytokines than those with the leishmaniasis parasite.

Similar studies will be necessary to determine if mosquito saliva has a similar potential, says Peter Billingsley of Sanaria in Rockville, Maryland, a company currently testing a malaria vaccine that uses an irradiated form of the parasite. “It would be really great if it did,” he says.