A team of researchers have developed a novel immunization method that may induce fast and effective protection in humans against the life-threatening malaria parasite, Plasmodium falciparum.
The international team of researchers were from Singapore, The Netherlands and France.
"It is not practical to apply the experimental method used in our study as a means of vaccination," said Dr. Laurent Renia, lead researcher at the Singapore Immunology Network (SIgN).
"But, this method of immunization could be applied successfully to similar investigations to find biological markers which would indicate the extent of protection against malaria. It would thus advance the currently limited knowledge of what constitutes protective anti-malaria immunity in humans," added Dr. Renia, who played a pivotal role in the research project by conceptualizing the experimental protocol and designing and conducting the follow-up experiments.
Describing their study in New England Journal of Medicine, the researchers revealed that their experimental approach involved exposing two groups of healthy human subjects to mosquitoes once a month over a three-month period at the Radboud University Nijmegen Medical Centre in The Netherlands.
One group (vaccine group) was exposed to mosquitoes infected with the malaria parasite, P. falciparum, and the second group (control group) to uninfected mosquitoes.
During the period of exposure, the subjects were treated with chloroquine, an anti-malaria drug that prevented P. falciparum from multiplying in the blood.
Eight weeks after the last round of immunization and four weeks after the discontinuation of chloroquine administration, the researchers re-exposed the participants in both groups to infected mosquitoes, and tested for protection against P. falciparum.
The four-week period was considered to be sufficient for chloroquine levels to drop below that which might inhibit parasite multiplication and malaria development.
The scientists found that all individuals in the vaccine group had acquired complete protection against the parasite, while those in the control group who did not receive immunization developed parasitemia (parasites in their blood).
According to the researchers, the unique method of immunization allowed the human immune system to direct its response to eliminating the P. falciparum parasite at the earlier, liver stage of its life cycle.
To induce an immune response, whole and intact malaria parasites were used.
Other methods have used genetically inactivated parasites or parasites that had been weakened by radiation to induce anti-malaria immunity.
The researchers said that their unique immunization method showed a significant improvement over other experimental malaria vaccines that are currently used in clinical trials and that could induce up to only 50 per cent protection in humans.
They added that they also used their novel approach to examine and gain important insight into the protective anti-malaria immune response in humans, which is difficult to acquire, whether through previous exposure or vaccination.
The scientists said that studying the antibodies, biological substances and cells present in the human subjects from the time of pre- to post-immunization helped them identify a specialized group of parasite-specific immune cells that indicated protection against P. falciparum in humans.
The immune cells, known as pluripotent effector memory T cells, which can mediate the removal of pathogens from the body, were found in the blood samples of subjects who had been immunized and re-exposed to P. falciparum. The control group did not have these specialized cells.
These results indicate that these cells could serve as a biological indicator to check for malaria protection in humans during the stages of vaccine development.
"This is an elegant study which uses nature itself to tell us the answer to some basic questions regarding what can induce protective immunity against malaria," said Dr. Raymond Lin, senior consultant and Head of Microbiology at the Department of Laboratory Medicine of Singapore's National University Hospital.
"It shows that exposure to whole unmodified malarial parasites can protect against subsequent infection, while minimizing adverse events through the use of anti-malarial drugs. This provides hope for future vaccines and offers prospects of alternatives to conventional vaccine approaches. Also, the remarkable experiment studies infection in humans, using real parasites and real mosquitoes yet in a controlled and safe clinical trial setting. Future vaccine researchers will doubtless refer to this paper for guidance. Malaria is a major health threat in this region which Singaporeans are vulnerable to, so having world-class malaria expertise here is important to us," he added.
SIgN Scientific Director Paola Castagnoli, Ph.D., said: "Professsor Renia has made some very significant findings that will contribute to a better understanding of the anti-malaria immune response in humans. His links with important international research centers and hospitals also demonstrate how collaborations that cross national borders can lead to fruitful and meaningful research outcomes. Certainly, such partnerships will help SIgN build up a strong platform in basic human immunology research that will better translate results into medical applications, and advance the search for cures to urgent medical problems."