December 27, 2013
Boosting An Existing Malaria Vaccine By Mixing It Up
Brett Smith for redOrbit.com - Your Universe Online
According to a study published in the journal PLOS Pathogens on Thursday, a prominent malaria vaccine could be drastically improved by utilizing the right mix of proteins taken from the surface of the virus.
The study researchers focused on the virus’ AMA1 protein, which the human body recognizes and uses to stimulate an immune response. However, the protein exists in multiple strains – causing problems for researchers looking to produce a wide-ranging vaccine.
To reach their breakthrough, the scientists tested different combinations of AMA1 from various strains for their capacity to stimulate different antibodies. The study team discovered that a blend of AMA1 proteins from three different strains produced an antibody reaction that was more wide-ranging than the total brought about by four individual strains.
The researchers also found that a four-strain blend called Quadvax produced antibodies that affected a range of pathogens, including some strains that were not represented in the Quadvax mix. These Quadvax-induced antibodies were found to restrain the development of 26 different strains. The study team suggested that "the combination of four AMA1 variants in Quadvax may be sufficient to overcome global AMA1 diversity.”
In addition to a high amount of variation, AMA1 also confounds malaria researchers by having less variable exposed parts, or epitopes, on its surface. The researchers found that Quadvax-yielded antibodies not only worked against the variable epitopes; they were also effective against the less-variable epitopes of the AMA1 protein. The researchers noted that Quadvax appeared to boost the induction of an antibody response in lab animals to the less-variable parts of the protein. The net result was the production of broadly active antibodies rather than strain-specific antibodies.
"We had set out to study broadening of antibody responses achieved by mixing AMA1 proteins and were surprised and delighted to find not only greater variety of strain-specific antibodies but also increased antibodies against (less-variable) epitopes were induced by the Quadvax,” the study authors wrote. “Perhaps even more exciting, when mixed, combinations of these antibodies were synergistic in their broad inhibition of many parasite strains.”
“(The) epitopes described here can be targets for further improvement of the vaccine,” they added. “Most importantly, our data strongly supports continued efforts to develop a blood stage vaccine against malaria.”
The study team speculated that a vaccine containing a few diverse AMA1 strains could provide universal coverage by sending an immune response towards specific epitopes. They said follow-up studies should focus on human-use formulations of Quadvax for testing in primate models.
In October, drugmaker GlaxoSmithKline (GSK) announced it would be seeking regulatory approval for a different malaria vaccine that recently delivered promising results in a large-scale trial conducted across Africa. The new vaccine – dubbed RTS,S – would be the world’s first malaria vaccine and could significantly boost public health in parts of Africa where malaria runs rampant.
"In Africa we experience nearly 600,000 deaths annually from malaria, mainly children under five years of age," said Halidou Tinto, a principal investigator from one of the trial sites and chair of the committee that oversaw the RTS,S trial. "Many millions of malaria cases fill the wards of our hospitals. Progress is being made with bed nets and other measures, but we need more tools to battle this terrible disease."