Synthesis, biological and immunological properties of cyclic peptides from Plasmodium falciparum Merozoite Surface Protein-1

Ring raises hopes for a malaria vaccine.

The malaria parasite (Plasmodium falciparum): vaccine designers have copied its key. Credit: © Aventis Pasteur

A molecular loop is looking like a promising candidate for the much-needed malaria vaccine. Developed by scientists in Colombia and Switzerland, the protein-like molecule primes a monkey's immune system, at least, to defend itself against the malaria parasite Plasmodium falciparum¹.

Malaria kills 2 million-3 million people a year, mostly children in developing countries. Drug resistance in P. falciparum is so widespread that malaria is now harder to control than it was 20 years ago. A vaccine would be the most cost-effective and convenient approach. As yet, none exists.

Manuel Patarroyo of the Fundacion Instituto de Immunologia de Colombia in Bogota and co-workers have devised a small molecule that resembles the protein MSP-1. P. falciparum uses MSP-1 to latch onto human red blood cells - once attached, it invades the cell, multiplies, and later bursts out ready to infect other cells.

Other vaccines in development²are also seeking to copy crucial parts of MSP-1. But a good mimic is more than just a copy of part of the protein's chain-like chemical structure. The chain also has to fold up in the right way.

Patarroyo and colleagues encourage this folding by linking the ends of their peptide chain into a loop, making it less floppy and less apt to adopt the wrong shape.

This cyclic structure has another advantage. Enzymes in the blood that dismantle and recycle proteins quickly break down small peptides. Lacking loose ends, the cyclic peptide is more resistant to these, and so lasts longer.

The researchers tested their molecule in monkeys. It elicited antibodies that spotted and stuck to real MSP-1 proteins from P. falciparum, marking them for destruction. This suggests that the cyclic peptide might confer protection against the parasite.

Only one potential malarial vaccine, called Spf66, has reached the field trial stage in humans. But the results from Africa and Southeast Asia were disappointing, and the vaccine field is still wide open.

It is still very early days for the new candidate. The real test is how it performs in humans, and such trials are a long way off. Finding a way to administer the ring-shaped mimic will also be crucial to success, but it has some design features that could be useful in the continuing search for malaria preventatives.