Malaria, caused by the protozoan Plasmodium, is responsible for more suffering and death across the world than any other parasite. It is a mosquito-borne infection that kills more than 1 million people annually, most of these children under the age of 5. Even when a person survives malaria, the infection can incapacitate a victim for several weeks. Over three billion people, most living in tropical regions, are exposed to malaria, and 500-600 million clinical infections occur every year.
U.S. military forces are at great risk of developing malaria while deployed in endemic areas. In fact, more person-days were lost among U.S. military personnel due to malaria than to bullets during every military campaign fought in malaria-endemic regions during the 20th century. Malaria also is a major threat to non-military travelers, who face this infection as likely the single greatest health risk associated with travel. To address this threat, researchers within the IDD have been investigating methods to control and conquer malaria for more than two decades. This comprehensive research program is at the forefront of malaria research worldwide.
Malaria is a complex parasite with a composition of proteins 300 times more diverse than the viruses that commonly infect humans. Like viruses, the malaria parasite requires a host to live, but unlike most viruses for which vaccines exist, the parasite chronically infects its human host, avoiding the immune system and living in the blood for many years if not treated.. As a result, the parasite has evolved to co-exist with its human host, making it very difficult to stimulate the immune response effectively with a vaccine. The malaria life cycle is also more complex that the life cycle of most viruses and bacteria; in order to work effectively, it may be necessary for a vaccine to induce an equally complex immune response that attacks the parasite at multiple stages. NMRC researchers realized the need for an innovative approach if we are ever to overcome this health threat. As one important initiative, the Malaria Program played a key role in the Malaria Genome Project, a consortium that determined the entire genetic sequence of the most deadly of the four human malaria parasites, P. falciparum.
The primary objective of the Navy Malaria Program is to develop a vaccine that kills the parasite during its first few days of development in the liver, before it breaks out into the blood. If this approach is successful, it will prevent the clinical manifestation of malaria, which occurs only in conjunction with blood stage infection and not with the liver stage. Such a vaccine would benefit deployed military personnel as well as travelers and other non-immune populations. At the same time, the program is investigating vaccines that would target blood stage infection to limit the severity of symptoms associated with this stage. Both liver and blood stage vaccines, if deployed in endemic areas, could alleviate much of the suffering caused by this parasite in tropical countries.
The program’s strategy is based on the idea that protective immunity will depend on using multiple antigens to induce both cellular and humoral immunity. We are characterizing several promising Plasmodium antigens in a variety of antigen delivery platforms, including plasmid DNA, vaccinia vectors, adenoviral vectors, Venezuelan equine encephalitis replicons, and recombinant proteins. We are testing heterologous prime-boost immunization strategies to find effective combinations of these antigens and vectors. We are using genomic and proteomic strategies to identify novel proteins with potential as vaccine antigens. We are also investigating the protective potential of attenuated malaria parasites.
The Malaria Program’s activities range from discovery research, in which we try to understand the nature of protective immunity, to clinical trials of candidate vaccines, carried out in our clinical trials center on the campus of the National Naval Medical Center. Successful vaccines can be transitioned to testing in field settings, with collaborating institutions in Africa, Asia, and South America. The Malaria Program also benefits from the Navy’s overseas laboratories, which allow study of the epidemiology of parasite in its native habitat, and also help to coordinate field testing of novel vaccines and drugs.