Shankar Swaminathan, Ph.D., is currently a postdoctoral fellow at the Hamilton Eye Institute, University of Tennessee Health Science Center in Memphis, TENN. His interest in Malaria therapy stems from his experience in a technical business development role while working for a pharmaceutical company.
Recently, in an unfortunate development, the malaria vaccine stumbled along its “PATH”: The most advanced and first-ever candidate malaria vaccine in a phase 2 clinical trial, RTS,S/AS01E (aka Mosquirix), demonstrated a waning efficacy over time. The results were published in the March 21 New England Journal of Medicine. This study was supported by the Program for Appropriate Technology in Health (PATH) Malaria Vaccine Initiative (MVI) and the Wellcome Trust.
According to the latest World Health Organization (WHO) estimates, there were about 219 million cases of malaria in 2010 and an estimated 660,000 deaths. Africa is the most affected continent with about 90% of all malaria deaths. A number of vaccines have been under development to bridge gaps in the existing arsenal against malaria. A summary of the current vaccine development is available in the WHO “rainbow tables.” RTS,S/AS01E is one of several potential vaccines under development that target the pre-erythrocytic stage of the disease engineered using genes from the outer protein of the Plasmodium falciparum malaria parasite.
Work on the RTS,S vaccine began a quarter of a century ago within the U.S. military, with development since 2001 being carried out by a public-private venture between the PATH MVI (supported by the Bill & Melinda Gates Foundation) and GlaxoSmithKline. In November 2012, results from phase 3 tests on 6,500 infants showed that the RTS,S vaccine only protected about a third of infants, compared with success rates of 47% to 55% in children between the ages of 5 and 17 months. This is also a matter of concern as the youngest age groups are most prone to the disease! The latest setback is reported from a phase 2 follow-up study on 320 Kenyan children, which found that in the first year after vaccination, protection against malaria was 43.6 percent, which dropped to zero by the fourth year. It was also found that the more often a child was exposed to malaria, the less effective the vaccine appeared to be. Interestingly, it was also found that, for every 100 vaccinated children, 65 cases of clinical malaria were averted. It has been noted that the Kenya study was small and used data from just one of many trial sites. The ongoing phase 3 pivotal study, the results of which are expected by the end of 2014, involves 15,460 children and is expected to provide meaningful insight.
While researchers in Africa and elsewhere were grappling to come to terms with these results, path-breaking progress was being made elsewhere. A group of researchers from the United States, Australia, Europe, and Asia reported discovery of a promising new compound ELQ-300. Another group based out of India reported identification of three key parasite antigens that elicited potent inhibition against P. falciparum strains. Recently, researchers from Japan reported development of an efficacious dry powder vaccine, BK-SE36, from a genetically modified protein found inside the parasite. These new chemical entities provide a great deal of promise, as we wait until the end of 2014 for more substantial results from the vaccine trial.