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Malaria vaccine strategies get boost

December 18, 2006 By Heidi Ledford This article courtesy of Nature News.

Money and research results both on the up.

Christmas came early last week to researchers who aim to conquer malaria the mosquito-borne disease that kills over a million people every year. In a first-ever summit on the disease at the White House, US President Bush announced an expansion of his Malaria Initiative, which has dedicated an extra US$1.2 billion to cut malaria-related deaths by 50% in targeted African countries within five years. The number of targeted countries has now expanded to fifteen from last year's seven.

And the Bill & Melinda Gates Foundation a charity set up by Microsoft founder Bill Gates and his wife Melinda announced an additional $83.5 million contribution in grants towards science aimed at conquering the disease. Including these grants, the Gates Foundation has thus far committed more than $750 million to fighting malaria.

Much of the Gates Foundation money will go toward developing vaccines. Despite more than twenty years of research in this area, no vaccines have yet made it through the final stage of drug testing and onto the market. But some 20 trials are in progress and the effort continues. The World Health Organization announced earlier this month that they intend to devise a vaccine that can protect 80% of the inoculated by 2025.

To meet those goals, some researchers are exploring fringe ways to keep the disease in check including using whole malaria parasites to prompt the human immune system, or trying to vaccinate mosquitoes instead of people against the disease-causing agent.

Leading candidate

Designing a vaccine against malaria has been difficult. Vaccines work by exposing the immune system to a disabled pathogen or a component of that pathogen, in hopes of prompting the immune system to recognize it. But the parasites that cause malaria of which Plasmodium falciparum is the deadliest have four stages to their lifecycle. A vaccine against one stage may not be effective against another.

Candidate vaccines have generally done a poor job of provoking an immune response, adds Louis Miller of the Malaria Vaccine Development Branch at the National Institutes of Health in Rockville, Maryland. Exactly why this is remains a mystery.

The most promising vaccine currently in trials is called RTS,S, which has been in development for about twenty years and is designed to cue the immune system to recognize a protein found on the parasite when it is initially injected into the bloodstream by a carrier mosquito.

RTS,S, which is being developed by GlaxoSmithKline Biologicals based in Belgium, has already been tested in humans and was able to reduce the rate of severe malaria by 58% in children six months after inoculation. The vaccine is expected to enter the final stages of clinical trials in mid-2008. Right now it's the lead candidate vaccine," says John McNeil, scientific director of the Seattle-based PATH Malaria Vaccine Initiative. "But we're always looking for improvements."

The whole story

An alternative technique is being developed by Sanaria, a company based in Rockville, Maryland. They aim to produce weakened forms of the whole parasite that are suitable for use as a vaccine.

Use of an entire pathogen to train the immune system is nothing new when it comes to viral or bacterial infections. But the malaria parasite's complex lifecycle makes it difficult to reproduce in the lab, and so difficult to manufacture enough for a vaccine. Stephen Hoffman, Chief Executive Officer of Sanaria, says that over the past three years, the company has been working to boost their production of the parasite at the sporozoite stage the stage at which it is first injected into the human bloodstream by mosquitoes. They can now do this efficiently enough to start trials in humans, they say. Hoffman hopes to begin clinical trials in 2008.

"It's the old, tried and true method of making a vaccine," says Hoffmann. "The problem has been that everyone thought it was not possible to produce a malaria vaccine based on that method."

The Malaria Vaccine Initiative announced last week that they would be partnering with Sanaria and bringing $29.3 million from the Gates Foundation along with them.

Pass it on

Meanwhile, back at the National Institutes of Health, Miller and his colleagues have been working on a different approach to vaccination using human blood as a way to vaccinate mosquitoes. Mosquitoes that drink the blood of inoculated patients would pick up the immune system proteins designed to target and destroy the malaria parasite, hopefully killing off the disease before it is passed on to people.

Miller has been focusing on a protein that is present on the surface of cells in the parasite during the stage at which it penetrates the mosquito's stomach. Coupling proteins together, Millers' group has found, makes a promising boost in immune response when tested in mice.1

Miller acknowledges that this method stands a poor chance of eradicating the disease in Africa, where the prevalance of disease is very high. But the approach may be very useful in Asia or Latin America, where the parasite is less common.

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  1. Kubler-Kielb A., et al. Proc Natl Acad Sci, doi:10.1073/pnas.0609885104 (2006).


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