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February 14, 2005 

Refining the Malaria Vaccine Agenda

Usually when malaria scientists gather to discuss vaccines, their conferences are heavy on vaccinology but light on the foundation of vaccine development: the body's immune response to the parasite. In helping to organize the malaria conference held Feb. 8-11 at the Johns Hopkins Bloomberg School of Public Health, Fidel Zavala, MD, wanted something different.

"This was essentially a meeting to discuss the immunology of malaria," says Zavala, professor, the W. Harry Feinstone Department of Molecular Microbiology and Immunology (MMI), about the workshop, Immunology of Malaria Infections: Implications for the Design and Development of Malaria Vaccines. "While always keeping vaccine development in the back of our minds, this was a chance for us to stop a little bit and think, and make sure we know everything that will be necessary for us to define and develop malaria vaccines."

Malaria researchers listen to the latest in vaccine development.

Malaria researchers listen to the latest in vaccine development.

Eleanor Riley, PhD, agrees about the underpinnings of conference. "The aim of this meeting is not for the participants to do what we all normally do at a meeting, which is to stand up and try to impress one another. Instead, the idea here is to really critically review all the data we have and to figure out what the basic biology is when the [malaria] parasite meets the body's immune system."

Unanswered Questions about the Immunology of Malaria
Riley, professor of Immunology at the London School of Hygiene and Tropical Medicine, goes on to say, "We really don't know, for instance, if we need a vaccine that produces antibodies or if we need a cell-mediated response." A cell-mediated response is one where the body's white blood cells are "trained" to kill a particular pathogen. These white cells, however, can then also do damage to host cells such as red blood cells, liver and brain cells. If this kind of immune response gets out of control, it can cause serious illness, notes Riley. "We're always having to weigh-up how much damage to the host we're prepared to accept."

Zavala can also recite a list of lingering questions that have stumped malaria scientists for decades, among them: How do the body's T-cells actually kill the liver cells that are infected with the parasite? "Understanding this would give a big boost to vaccine development," he notes. "The better we understand the immunology of the parasite, the better vaccine we can develop."

A Different Kind of Conference
The workshop planners took pains to design the conference so that the participants would interact at length. To this end, attendance was limited to about 50 participants and, says Riley, "we insisted on a round table, so everyone was facing each other. People won't talk to each other if they are sitting in long rows with their backs to one another." Among the 50 attendees, 12 scientists were from Europe (England, Denmark, Sweden and France), 7 were from Australia, 3 from Canada, 3 from Africa and 2 from Asia.

After each one-hour presentation by an immunologist, the malaria researchers working in that area then gave 5-minute presentations, using only their unpublished data. Then, at least one hour of every section was reserved just for discussion.

This more informal style has led to some pleasant surprises. "People have pulled out little bits of data that only they know," says Riley. "One-off findings that they'll suddenly drag out of their cupboard, saying, 'Yes! I know that! I know the answer to that question.' "

Douglas J. ("D.J.") Perkins, PhD, appreciated being able to get together with people whose research is coming from a slightly different direction. Perkins, assistant professor of Infectious Diseases and Microbiology, University of Pittsburgh, works in the interior of western Kenya studying the molecular basis of immune dysfunction in individuals co-infected with malaria and HIV. "There's been a big split between the animal models and the human data, and so this meeting has brought these two communities together to discuss whether the basic science results from animal experiments can be used to develop very focused experiments in humans."

John  Sacci, PhD, is also enthusiastic about the workshop's format. "There are always big meetings, of course—but big meetings are . . . big meetings: People deliver lectures, and then there's only time for a few questions." This workshop, says Sacci, assistant professor of Microbiology and Immunology at the University of Maryland School of Medicine, has been just the opposite: a few formal presentations, and then the rest of the time everybody dives into a discussion about the topic. "We must find out if we are going in the wrong direction and, if so, figure out how to change our direction."

The Future of Malaria Immunology
Where do the participants go from here? It's difficult to tell, says Riley, because no one can really control the research agenda. "You can't [have a workshop like this one] very often because you have to leave it to people to re-shift their agendas. We can only shift our own research agendas voluntarily, as a community. And then getting the funding to do it and seeing if your new direction makes a difference—it will take at least three or four years to see if any of the ideas picked up here are going to pay off."

One thing is certain: The participants never lose sight of the gravity of their task. Professor Kevin Marsh, who heads the Wellcome–KEMRI (Kenya Medical Research Institute) Research Programme in Kilifi, Kenya, says, "Although we've eradicated malaria around the fringes—in the U.S. and Europe, for example—its effects in Africa are just as devastating as they've ever been. If anything, it's more so because malaria mortality has doubled in Africa over the last 15 or 20 years, due to the parasite's increasing resistance to the main antimalarial, chloroquine."

Diane Griffin, MD, PhD, professor and chair of MMI, who oversees the Johns Hopkins Malaria Research Institute, said, "The Johns Hopkins Malaria Research Institute was very pleased to host this meeting. This workshop has taken an innovative approach to identifying the issues in malaria immunology that are important for recovery from infection and for protective immunity. The interactive discussions have been very useful and will likely influence future malaria immunology research in important ways." --Rod Graham

"Immunology of Malaria Infections: Implications for the Design and Development of Malaria Vaccines" was supported by the Wellcome Trust, the Malaria Vaccine Initiative (from the Bill & Melinda Gates Foundation) and the Ellison Medical Foundation