A United Front
by Sarah Stone Wunder
February 2008
New partnerships aid the global fight against malaria.
Photography by
The fight against malaria received extra support in 2007 with the addition of new initiatives, partnerships and facilities geared toward malaria vaccine development. These new initiatives come at a time when, according to the World Health Organization, malaria claims more than 1 million lives every year, the majority of which are children.
In December, the Infectious Disease Research Institute (IDRI) received a $29.9 million, five-year grant from the Bill & Melinda Gates Foundation. IDRI is a Seattle, Washington, USA-based non-profit scientific research institute. The group will use the funds to provide adjuvants for priority malaria vaccine candidates. Adjuvants are compounds that boost the immune response that is elicited in response to a vaccine candidate.
According to Darrick Carter, director of formulations for the IDRI, the discovery of Toll-like receptors has enabled research aimed at identifying next-generation, specific adjuvants.
“Toll-like receptors detect molecular patterns from pathogens,” Carter says. “They are like a burglar alarm for the immune system. With this system, the immune system can recognize that it was infected by something without identifying the specific threat and turn on a vigorous response. What people have realized is that if you use Toll-like receptors agonists, one can kick this burglar alarm on.”
As a result, Carter says, adjuvants can be combined with a vaccine to help the immune system begin vigorously responding to the vaccine. These receptor agonists are essential for vaccine development, but they can be difficult to acquire, especially for small pharmaceutical companies or non-profits, he says.
According to Carter, adjuvant research is essential because it can bring researchers closer to developing an effective malaria vaccine, as well as further developments for other diseases. The goal is to develop adjuvants that are sufficiently effective to allow for abbreviated dosing schedules—especially for vaccines targeted to children—so that protective immunity can be achieved in a single dose.
“We realize now that one of the reasons that our malaria vaccines developed to date aren’t as potent as they should be is that it’s possible that they may have the right antigens, but not the right adjuvants, so they’re not kicking off the right response,” he says. “And that is a theme that we have seen in malaria, tuberculosis and HIV, in that people might have the right molecules, but the immune system is not responding properly. What we want to do is use the right combination of adjuvants and antigens to direct the immune system to respond in the right way, therapeutically.”
Carter says the Gates Foundation was interested in working with IDRI because of its recent focus on adjuvant development. “The Gates Foundation would like their malaria program vaccines to really start protecting at much higher levels than they are now,” he says. “So they’ve contracted IDRI to do this adjuvant development, and try to secure licenses from for-profits and to put it all together with an antigen for malaria so we can make a much better malaria vaccine.”
To work toward this goal, IDRI is in talks with select pharmaceutical companies to get access to their Toll-like receptor agonist technology, as well as developing its own proprietary technology, Carter says. In addition, the organization is working with the Malaria Vaccine Initiative (MVI) to select antigens.
‘Never Been So Close’
The Path Malaria Vaccine Initiative (MVI), which is a global program at PATH, works to accelerate the development of promising malaria vaccines and to ensure their availability and accessibility in the developing world. Dr. Christian Loucq, director of MVI, says IDRI is one of many groups MVI has found to aid in the development of effective malaria vaccines. One of MVI’s leading partnerships is with GlaxoSmithKline biologicals. The vaccine candidate that is furthest along—and the one that makes Loucq say that the world has never been so close to a malaria vaccine—is RTS,S.
MVI is supporting the clinical development of RTS,S, a proprietary vaccine of GlaxoSmithKline. The RTS,S vaccine candidate is currently in Phase II trials, and is expected to enter Phase III by the end of 2008, Loucq says.
“We are going to embark on a multi-center trial in Africa with 10 centers in seven countries, and we are going to include 16,000 infants and children in the trial,” Loucq says. “So it is a major adventure that we are venturing into. That’s the first malaria vaccine to undergo such a large multi-center trial. If everything goes well, GSK would be able to file [for regulatory approval] as early as 2011.”
In addition to its work with GlaxoSmithKline, MVI has also recently partnered with biotech company Sanaria to open a clinical manufacturing facility to produce a vaccine that uses a weakened form of the malaria parasite, Plasmodium (P.) falciparum.
The manufacturing facility, which officially opened in October, has been constructed to allow scientists to rear live, aseptically produced mosquitoes, feed them blood containing the malaria parasite, irradiate the insects to weaken the parasites, and then harvest the parasites from the mosquito salivary glands. The goal is to use these parasites as the main component of a “whole-parasite” vaccine to be tested in an initial clinical trial in adult U.S. volunteers in 2008.
“This is an important day because it signifies that Sanaria is now equipped to answer two key questions about a whole-organism vaccine,” Loucq said in an October 2007 press release. “Can this vaccine be reproducibly manufactured, and if it can, will the vaccine work in experimental conditions?”
The initiative includes partners in Africa, Asia, Europe, Australia, and North America. The new facility is located in Rockville, Maryland, USA.
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