A shot in the arm for treatment options

2 Feb 2010

A ‘whole parasite’ strategy could lead to a vaccine for one of the world’s deadliest diseases

Fig. 1: Photograph of a female Anopheles mosquito, which is a vector of malaria, feeding on a human host.

Fig. 1: Photograph of a female Anopheles mosquito, which is a vector of malaria, feeding on a human host.

Photo: James Gathany

A novel method of immunization provides fast and effective protection against malaria, according to a double-blind, placebo-controlled study published in the New England Journal of Medicine by an international team of researchers that included Laurent Rénia of the A*STAR Singapore Immunology Network.

Malaria is a mosquito-borne infectious disease caused by parasites of the Plasmodium genus. Endemic in many parts of the developing world, malaria causes up to 500 million infections and more than one million deaths annually. Malaria parasites have a complex life cycle with numerous stages, each with a different genetic profile. Immunity is therefore difficult to acquire and, despite decades of research, an effective vaccine has yet to be developed.

In rodents, inoculation with intact sporozoites—the infective form carried by mosquitoes—during treatment with the anti-malarial drug chloroquine has been shown to kill the parasite in certain stages of its life cycle, and to produce effective protection against malaria.

In their immunization study, Rénia, in collaboration with researchers from the Netherlands and France, investigated whether this approach would also induce protection against the disease to humans.

They recruited 15 healthy volunteers and randomly assigned ten to the vaccine group and the remainder to the control group. Both groups received a standard regimen of chloroquine. During this immunization phase, the researchers exposed the vaccine group to mosquitoes infected with Plasmodium falciparum, and the control group to uninfected mosquitoes (Fig. 1). Both groups were exposed once a month for three months.

Four weeks after the chloroquine treatment, Rénia and co-workers again exposed, or ‘challenged’, both groups to infected mosquitoes, and monitored them for symptoms and signs of malaria. They also took blood samples to test for presence of the parasite and to analyze the immune response.

Following the second exposure to infected mosquitoes, the researchers detected P. falciparum in all five controls but none in the vaccine group. Those who received the experimental vaccine developed an antibody response to both the liver-infecting sporozoites and the blood-stage parasite. Three also developed antibodies against a third stage of the life cycle.

The researchers believe that their method is effective because it presents the immune system with a bigger variety of antigens from different stages of the parasitic life cycle, and they will further investigate the ‘whole-parasite’ immunization strategy.

“This study exemplifies the commitment of the Singapore Immunology Network to build strong platforms in human immunology and infectious diseases for better translation of results into medical applications,” says Rénia.

The A*STAR-affiliated authors in this highlight are from the Singapore Immunology Network.

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Roestenberg, M., McCall, M., Hopman, J., Wiersma, J., Luty, A. J. F., van Gemert, G. J., van de Vegte-Bolmer, M., van Schaijk, B., Teelen, K., Arens, T., et al. Protection against a malaria challenge by sporozoite inoculation. The New England Journal of Medicine 361, 468–477 (2009). | article

This article was made for A*STAR Research by Nature Research Custom Media, part of Springer Nature