12 November 2002 16:30 GMT

by Edward Susman

[caption and credit]

Denver - Preliminary results from phase I clinical trials of two vaccines designed to combat Plasmodium vivax infection are promising, researchers reported today at the annual meeting of the American Society of Tropical Medicine and Hygiene here.

Although P. vivax causes a clinically less severe malaria then does P. falciparum, it is the most geographically distributed of the malaria parasites, and affects as many as 100 million people around the world.

One vaccine, targeted at the circumsporozoite protein (CSP), aims to prevent P. vivax infection, while the second vaccine candidate prevents transmission of the parasite to others.

The CSP vaccine consists of a synthetic peptide that is mixed with the adjuvant montanide ISA-720, according to Socrates Herrera, a researcher at the Instituto de Immunologia, Universidad del Valle, in Cali, Colombia - an area that has endemic P. Vivax malaria.

The naked peptide produced a small antibody response in animal models, but that response was increased when the peptide was co-administered with montanide, Herrera said.

Montanide stimulates the body's immune response to the peptide and also keeps the peptide in the cell tissues longer, extending that response, explained John Adams, associate professor of biological science at the University of Notre Dame in Indiana.

In the current trial, 60 subjects are receiving the CSP vaccine in three doses. The first patients received 10 micrograms of the vaccine at baseline, at two months and at eight months. Other groups of patients received either a 30-microgram, or a 100-microgram dose of the vaccine on the same schedule. There are no adverse reactions to date, Herrera said.

The second vaccine follows an 'altruistic' vaccine approach," said Barbara Sina, a project manager with the Fogarty International Center of the US National Institutes of Health. It will not help the person who is already infected, but is designed to prevent disease transmission.

Phase I trial for the vaccine began enrolling subjects in September of this year, said Takafumi Tsuboi, associate professor of parasitology at the Ehime University School of Medicine in Japan.

The vaccine candidate interferes with molecular signaling through a surface protein during the reproduction stage of the parasite's life cycle. When mosquitoes feed on the blood of the serum of animals or humans who have been inoculated with the Pvs25 vaccine, the parasites are unable to form oocysts.

Pre-clinical studies showed nearly a 100% ability to prevent the formation of oocysts, Tsuboi said. Even when the vaccine is diluted eight-fold, he added, the transmission of oocysts formed in the mosquitoes is reduced by more than 70%.

Still, said the NIH's Sina, the general feeling is that the transmission-blocking vaccine will not be administered alone, but with other vaccines.

Picture caption and credit:
Plasmodium vivax trophozoite in blood smear, CDC.

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