No infectious disease kills more people in the world than malaria. As a consequence, there has been a great deal of interest in making a malaria vaccine. It hasn’t been easy. The most advanced candidate vaccine to protect against malaria is the so-called RTS,S/AS01 vaccine, which contains the circumsporozoite of the malaria parasite (expressed by the parasite during the early sporozoite stage) and an adjuvant that includes monophosphoryl lipid A (a detoxified lipid A moiety that is also used in the human papillomavirus vaccine, Cervarix®) and saponin. This vaccine has been shown to be only about 50-60 percent effective at preventing clinical disease, and protection appears to wane over time.
A recent study published in the New England Journal of Medicine reveals another potential problem regarding this vaccine (Neafsey DE, Juraska M. Bedford T, et al. Genetic Diversity and Protective Efficacy of the RTS,S/AS01 Malaria Vaccine. N Engl J Med. 2015 Nov 19;373(21):2025-37). It has been known that the immunologic sites (epitopes) recognized by T and B cells can differ among different malaria strains (called polymorphisms). What wasn’t clear was whether those polymorphisms made a difference in vaccine efficacy. Neafsey and coworkers showed that the RTS,S/AS01 vaccine was more effective at protecting against clinical malaria when the vaccine strain matched the circulating strain than when it didn’t. The differences weren’t large, about 10-15 percent less efficacy, but they were reproducible.
In an accompanying editorial, Christopher Plowe argued that a drop in efficacy of 10-15 percent wouldn’t be as bad if the vaccine were 90 percent effective against matched strains (Plowe CV. Vaccine-Resistant Malaria. N Engl J Med. 2015 Nov 19;373(21):2082-3). But the RTS,S/AS01 vaccine is only about 60 percent effective against matched strains, so a 10-15 percent drop is more significant, especially given that immunity can wane over time. The news isn’t all bad, argues Plove. Efficacy can arguably be improved by including a broader range of circumsporozoite proteins that account for different polymorphisms.