Navy Medical Researchers Explore Preventative Malaria Vaccines

Capt. Thomas Richie, director of the Navy’s Malaria Program at the Naval Medical Research Center, Silver Spring, MD and the research coordinator of the U.S. Military Malaria Vaccine Program.

By: Capt. Thomas Richie, director of the Navy’s Malaria Program at the Naval Medical Research Center, Silver Spring, MD and the research coordinator of the U.S. Military Malaria Vaccine Program

Protecting our fighting forces against infectious threats such as malaria is why Navy Medicine and our sister services continuously conduct medical research. We want to provide our forward-deployed forces with the best in force health protection.

Military personnel are at risk of developing malaria, a multi-staged parasitic infection, while deployed in endemic areas and we continue our research work to provide the best safeguards for them. Malaria is found in most tropical regions of the world, and also some subtropical areas such as Afghanistan and Korea. The malaria parasite is transmitted by the bite of the female anopheles mosquito. This infectious threat can compromise the integrity of our military missions by sickening our troops, and this can happen within ten or twelve days of arriving in the operating theatre. The worst cases can lead to death.

The importance of malaria to the U.S. military was illustrated by the mission-altering evacuation of 43 Marines from the West African country of Liberia in 2003. Five of these Marines required intensive care before recovering, and in December 2009, a Seabee also deployed to Liberia died of malaria. The U.S. Military Malaria Vaccine Program (USMMVP) is a combined Army-Navy research and development initiative that represents more than 20 years of research with a focus on creating vaccines to prevent malaria.

We are following three different vaccine development approaches, all targeting the early stages of infection. The first target is when the parasite enters the human body from the bite of an infected mosquito and moves through the blood stream to invade the liver (sporozoite stage parasites) and the second target is when the parasite develops for 5 days or longer within the liver cells (liver stage parasites), before breaking out of the liver and moving back into the blood stream in another form. These early stages of infection do not harm the body or cause any symptoms, so if a vaccine targets them effectively, it will completely prevent any manifestations of infection. It is the later stages that grow in the blood that cause the clinical syndrome of malaria, leading to anemia and prostration, and in the severe forms of the disease, to organ failure, coma and death.

The first vaccine approach is to inject small quantities of key parasite proteins derived from sporozoites. These proteins are mixed with an immune-stimulating adjuvant to induce high levels of antibody. The second approach is to inject gene-based vaccines that induce strong cell-mediated immunity, a different arm of the immune system from antibodies that should be able to kill the parasites in the liver. The third approach is to inject live-attenuated parasites, using sporozoites (the parasite stage injected by mosquitoes) that have been weakened by radiation or genetic knock-out. Each approach has shown some degree of protection in human challenge trials. The highest protection, about fifty to ninety percent, has been achieved by immunizing with irradiated sporozoites that are delivered via the bites of mosquitoes, a cumbersome and time consuming vaccination process.

Because there is no established immunological correlate of protection, and no certainty which vaccine approach will yield our target of eighty percent or more protection, the USMMVP also maintains a scientific program focusing on discovering new antigens, identifying the mechanisms of immune-mediated protection, and exploring novel technologies such as bacterial vectors, nanoparticles, and improved compounds to stimulate the immune system.

A warfighter with malaria can be incapacitated for one to three weeks and some malaria infections can rapidly become life threatening if not promptly diagnosed and treated. In addition, warfighters can be exposed to more than one malaria species in today’s complex military operations. Despite having very effective drugs to treat individuals suffering from malaria, I feel the most cost-effective measure to fight this disease is to develop preventive malaria vaccines.

Photos: Naval Medical Research Center

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