'Cocktail' Approach Could Lead to Universal Malaria Vaccine

By mixing a key surface protein from a number of different strains of the malaria parasite, researchers say they have improved the effectiveness of a potential vaccine against the disease spread by mosquitoes.

A vaccine that targeted the AMA1 surface protein was effective in previous human testing, the researchers say, against only one strain of the protozoan Plasmodium falciparum - the malaria parasite - whereas their "cocktail" approach, using the protein from different strains, may lead to universal coverage against the microbe. The study was led by Sheetij Dutta of the Walter Reed Army Institute of Research in Silver Spring, MD. The AMA1 surface protein is needed by the malaria parasite to invade blood cells, and so cause disease; using it in a vaccine primes our immune system against the microbe. Earlier designs of the AMA1-based vaccines were too specific, Dr. Dutta's team says, but using just a few different strains broadens out the protective coverage of a potential immunization. The study found that using: 1. Three different parasite strains was better than using one or two. 2. Four strains gave additive effects that were greater than the sum of the parts.

Broad-spectrum effect. "Quadvax," the mixture of AMA1 proteins derived from four different parasite strains, produced a laboratory assay immune response that involved more antibodies than represented by the sum of response to each individual strain used alone. The antibodies elicited by the vaccine inhibited numerous parasites beyond those represented by the four strains of surface protein used. A total of 26 different parasite strains were inhibited by the Quadvax-induced antibodies, and the scientists suggest that the combination "may be sufficient to overcome global AMA1 diversity." The scientists conclude they "were surprised and delighted to find not only greater variety of strain-specific antibodies, but also increased antibodies against conserved epitopes." Epitopes are the exposed parts of parasite antigens recognized by our immune system, and conserved ones are derived from less variable regions of a parasite genome. Since such epitopes are identical across different strains, the scientists say, the resulting antibodies are broadly active rather than strain-specific.

The researchers add: "Perhaps even more exciting, when mixed, combinations of these antibodies were synergistic in their broad inhibition of many parasite strains." The newly discovered conserved epitopes described by the researchers can be targeted for "further improvement of the vaccine." They also urge that: "Most importantly, our data strongly supports continued efforts to develop a blood stage vaccine against malaria." Research adds to prospects of a malaria vaccine. The struggle to find an effective vaccine against malaria has included late-stage human trials run by pharmaceutical giant GlaxoSmithKline, which in October 2013 reported a protective effect for children for up to 18 months after vaccination.

The drug company's RTS,S vaccine is a step closer to being approved for use in 2014-2015, after reducing cases of clinical malaria in the trial by 46% in young children aged 5-17 months, and by 27% in babies aged 6-12 weeks. Meanwhile, research published in August 2013, which is not at such an advanced stage, has suggested a vaccine that could result in 100% protection. News in November 2013 from the CDC (US Centers for Disease Control and Prevention) revealed that US malaria cases had reached their highest in 40 years. The Plasmodium parasite lives in the gut of the female Anopheles mosquito and passes to humans through her bite.