Every time a mosquito bites you, she injects a bunch of goodies into your bloodstream. These ingredients help her to slurp up a meal by stopping your blood from clotting and keeping your blood vessels dilated. However, mosquito spit serves a more nefarious purpose as well. Scientists reported today that mosquito saliva causes far-reaching changes in the immune system that last for a least a week in mice after they’ve been bitten. This may explain how saliva from mosquitoes and other pests such as ticks and sand flies primes our bodies to be more vulnerable to diseases like malaria and dengue fever.
It’s concerning that mosquito spit has such a strong effect on the immune system. But there is a way we can fight back. Scientists are developing vaccines that will combat mosquito saliva itself rather than a single virus, bacteria, or parasite.
“You can try to protect against many, many different pathogens in one fell swoop, with one vaccine,” says Rebecca Rico-Hesse, a virologist at Baylor College of Medicine in Houston and coauthor of the new paper. “That way we could actually have some weapons against emerging viruses.”
To make such a weapon possible, we’ll need to learn more about how our immune systems react to mosquito saliva. One strength of the new study is that the mice in question were engrafted with human stem cells, giving them an immune system that more closely resembles our own, says Jessica Manning, an infectious diseases physician at the National Institutes of Health’s Malaria and Vector Research Laboratory in Phnom Penh, Cambodia. This gives us a clue as to what a human response to mosquito saliva might look like without having to dissect people’s bone marrow and spleens.
Previously, Rico-Hesse and her colleagues have seen that this type of mouse develops more severe symptoms of dengue fever after being bitten by mosquitoes than when the researchers injected the virus with a needle. This happens because our bodies have an allergic reaction to mosquito saliva (the reason we get those itchy red bumps).
“The virus present in that mosquito’s saliva, it’s like a Trojan horse,” Manning says. “Your body is distracted by the saliva [and] having an allergic reaction when really it should be having an antiviral reaction and fighting against the virus.” Thus, the immune system does not attack the virus as fiercely as it needs to. On top of this, the saliva attracts immune cells that are susceptible to the germ. “Your body is unwittingly helping the virus establish infection because your immune system is sending in new waves of cells that this virus is able to infect,” Manning says.
This time around, Rico-Hesse and her team exposed mice to mosquito spit without any trace of dengue. They discovered that the immune response to mosquito saliva lasts longer and ropes in more different types of cells than had previously been suspected, including ones from the bone marrow. Seven days after the mice had encountered mosquitoes, the team detected these immune cells traveling to the site of the bite. Since immune cells also migrate back to the marrow, it may become a reservoir for any viruses that happen to be lurking in mosquito saliva, Rico-Hesse speculates.
“We had no idea that saliva was doing all these things to make [the body] a better replication ground for the viruses or parasites,” she says. “Mosquito saliva has evolved to modify our entire immune system and it’s basically setting it up for pathogens to replicate easier and to cause more disease.”
It’s also possible that being constantly bitten by mosquitoes could have negative consequences for our immune systems even when the bugs aren’t carrying any viruses.
“There must be other effects that we haven’t even begun to measure,” says Rico-Hesse, who published the findings in the journal PLOS Neglected Tropical Diseases. “It opens up a whole can of worms in terms of what people are being exposed to when we’re being bitten by mosquitoes.”
Vaccines to stymie spit
So the sooner we can make a vaccine against mosquito spit, the better. As a first step, both Rico-Hesse and Manning are trying to figure out which proteins in mosquito saliva are responsible for helping pathogens infect us more easily. Other scientists are doing the same for sand fly and tick spit.
Their hope is to prevent bug saliva from messing with our immune system so our bodies will attack any germs carried along with it more effectively. “Perhaps your body is going to maintain that fighting stance… as opposed to launching into an allergic response,” Manning says.
Scientists would also add ingredients to the vaccine that would encourage the body to mount an even more intense response to destroy the pathogen. This strategy is used in many of today’s vaccines, including those for tetanus, hepatitis, and human papillomavirus, Manning says.
She and her colleagues have also been working with SEEK, a pharmaceutical company in the United Kingdom, to develop a vaccine against a handful proteins in spit from a mosquito that transmits malaria, Anopheles gambiae. They have begun testing the vaccine in people, and hope that it may be effective against spit from other kinds of mosquitoes as well.
“It would be a feat if there was a universal vaccine—one single vaccine for all mosquito-borne disease,” Manning says. However, creating a vaccine against one type of mosquito saliva is a more realistic goal for the next decade, she says.
Meanwhile, Rico-Hesse is focusing on spit from Aedes aeygpti, the mosquitoes that transmit dengue and a host of other ailments. “If we can get something to work against the Aedes aeygpti salivary proteins, not only could we be impacting the transmission of dengue but Zika, yellow fever, [and] all the other viruses,” she says.
One potential problem with saliva-based vaccines is that they may wear off quickly. There’s some evidence that people may be slightly less likely to get infected with malaria if they are constantly bitten by Anopheles mosquitoes. However, when these people leave town for a few months, the antibodies they have made against the mosquito spit disappear. So the immunity bestowed by a spit vaccine may not last very long on its own. On the other hand, for people who live in areas swarming with these mosquitoes, being bitten all the time may act as a kind of booster shot.
Ideally, we’d receive spit vaccines along with those designed to target particular diseases. But vaccines against mosquito saliva would come especially in handy to fight emerging viruses that we haven’t developed vaccines for yet. Typically, we can’t create new vaccines fast enough to halt an epidemic, Manning says. Scientists developed Zika vaccines at breakneck speed, but they still were not ready by the time the recent epidemic had waned. If we had saliva vaccines on hand, it could potentially help stem future epidemics, Manning says.
Rico-Hesse expects it will take at least 10 years to figure out which mosquito saliva proteins have the biggest impact on our immune system and see if immunizing against them does in fact prevent disease transmission. “We’re just at the beginning of understanding how saliva works in mosquito-borne diseases,” she says.
Still, mosquitoes kill about 1,700 people a day around the world, Manning says. And, as the Centers for Disease Control and Prevention recently reported, the number of cases of mosquito-borne diseases has only been rising in recent years in the United States. “Any dent that we can make in those numbers would be meaningful,” Manning says.