While the deaths from malaria are devastating, ranging in the hundreds of thousands annually, it is often the morbidity associated with this parasitic infection that can be viewed as even worse—decimating large populations and incapacitating members within endemic areas who are critical to its economic vitality. There are five different species of malaria parasites that infect humans, with Plasmodium falciparum causing the most deaths and Plasmodium vivax being the most widespread globally.
P. vivax has several unique features, but it is the parasite’s ability to form a dormant liver stage as well as its intractability toward laboratory culture that have stymied drug and vaccine development over the years. Now researchers from the Walter Reed Army Institute of Research (WRAIR) have recently published their results of testing a P. vivax malaria vaccine candidate in a human challenge model.
WRAIR investigators immunized 30 volunteers with three doses of the vaccine candidate. Immunized volunteers took part in WRAIR's well-established controlled human malaria infection (CHMI) model where they were bitten by malaria-infected mosquitoes. The efficacy of the vaccine candidate was then determined on the basis of whether or not volunteers developed malaria by looking at blood smears or if it took longer for malaria parasites to appear in the blood.
“This represents the first vaccine study to test the effectiveness of a P. vivax vaccine candidate in humans using controlled human malaria infection,” explained lead study author Lt. Col. Jason W. Bennett, research scientist at WRAIR.
The findings from this study were published recently in PLOS Neglected Tropical Diseases in an article entitled “Phase 1/2α Trial of Plasmodium vivax Malaria Vaccine Candidate VMP001/AS01B in Malaria-Naive Adults: Safety, Immunogenicity, and Efficacy.”
The research team acquired P. vivax-infected mosquitoes from collaborators in Thailand that were transported to WRAIR for the malaria challenge. The vaccine candidate was well tolerated in all volunteers and generated robust immune responses. Unfortunately, the vaccine candidate did not prevent malaria infection in volunteers; however, it did significantly delay the parasitemia in 59% of vaccinated subjects.
“Findings from the analysis of the immune response of vaccinated subjects have given us clues to improve vaccine candidates, and studies are now underway at WRAIR to develop next-generation vivax vaccines,” remarked Lt. Col. Robert Paris, M.D., director of the U.S. Military Malaria Research Program at WRAIR. “Vaccines and antimalarial drugs are both critical needs for the DoD to protect service members from malaria.”
Interestingly, the clinical data from this study is the first to show that differences in a person's genetics can result in primaquine treatment failure. Regrettably, despite this newly identified limitation, primaquine remains the only FDA-approved drug to treat the dormant liver stages of vivax malaria.
The WRAIR team is still optimistic that the results they have obtained from the current study will provide them with a road map toward an improved vaccine. Moreover, the investigators are dedicated and hopeful that their continued efforts will be fruitful in developing therapeutic products to eradicate and curb the transmission of various infectious diseases.