You might feel the bite, you might not, but an infected mosquito has injected you with a parasite named Plasmodium falciparum, a single-cell protozoa that quickly takes up residence in your body.
You don't feel a thing as the parasite infects your liver and begins to multiply. But then tens of thousands of parasites spill into your bloodstream and start eating their way through your red blood cells. You feed terrible. You have malaria.
By genetically-modifying these same parasites, researchers in Seattle recently created a vaccine that appears to be safe and effective in generating an immune response to malaria in a small study of human volunteers. The work is part of a global effort to eliminate the suffering caused by malaria through improved testing, treatment, vector eradication, and development of an effective vaccine.
Malaria is a significant threat to people of all ages who live in Asia and Sub-Saharan Africa or individuals bitten by an infected Anopheles mosquito. In one bite, the mosquito injects between eight to ten plasmodia parasites, just one of which can initiate a malaria infection. Even mild cases of malaria can cause flu-like symptoms and fever. Young children and babies can suffer lifelong disabilities from malaria, creating heavy social and economic impacts.
According to the World Health Organization (WHO), there were 212 million new cases of malaria reported and 429,000 deaths in 2015. In the US, approximately 2,000 cases occur each year, mostly to travelers returning from foreign countries.
Although the discovery that parasites cause malaria did not occur until 1880, the disease, so-named for bad air ("mal aria"), has plagued humanity for an estimated 4,000 years.
While we generally consider mosquitoes to be blood-sucking parasites, the Anopheles mosquito is also an insect host and vector that carries a parasite or bacteria. A parasite is an organism that takes its food at the expense of the host on which it feeds. Although you usually don't hear too much about them, there are a wide variety of parasites, including parasites transmitted by pets, like hookworms, Cryptosporidium, a parasite in untreated water, or pubic lice called "crabs" that are usually spread through sexual contact.
In research from the private, non-profit Center for Infectious Disease Research and the Fred Hutchinson Cancer Research Center in Seattle, scientists deleted three genes that allow P. falciparum to infect the liver and cause the symptoms of malaria.
There are many avenues scientists take to create vaccines. A live attenuated vaccination is made from a microbe that has been weakened enough that it cannot cause disease—but it can provoke your immune system to respond and create immunity to an infection. In this study, researchers created a genetically attenuated parasite by "knocking out" three genes, which they named GAP3KO.
Currently, there are malaria vaccinations in development in other labs. One vaccine contains fragments of the Plasmodia parasite and confers only partial immunity. Another vaccine uses whole, live attenuated parasites but carries a strong risk of full infection. In this study, the vaccine made from genetically modified parasites creates an immune response in human volunteers and did not lead to development of malaria, or significant symptoms or side effects.
The study, which was published in the journal Science Translational Medicine, involved ten human volunteers. All were between the ages of 18 and 50, healthy, with no previous exposure to malaria. Scientists infected Anopheles mosquitoes with the genetically modified parasite and placed about 200 in an enclosed chamber. The mosquitoes were allowed to feed on the forearm of each volunteer for ten minutes.
While the study was conducted for 28 days, volunteers were followed for six months. No significant adverse effects were reported, with the most discomfort caused by the significant number of mosquito bites suffered during exposure.
Subsequent analysis showed all volunteers developed antibodies against malaria. To further test the effectiveness of the gene-knockout, researchers combined plasma and serum from five volunteers to create a rodent model vaccine. Using mice engineered for susceptibility, researchers injected five mice for each subject. One day later, the mice were infected by 50 bites from infected mosquitoes. The immunization protected the mice against malaria infection.
"This report is a major advance in malaria vaccine development by providing the first evidence that genetically attenuated Plasmodium falciparum parasites are safe and immunogenic in humans," said Robert Seder of the National Institutes of Health (NIH), who was not involved with the research, in a press release. "Future studies demonstrating protective efficacy will be the next critical milestone for continued development of this promising vaccine approach."
GMOs sometimes get a bad rap from different quarters. In this case, a genetically-modified organism may save lives and ease the burden of malaria.