Fresh Hope for Malaria Vaccine from Newly Discovered Parasitic Antigens

Every year more than 28 million Americans travel to the nearly 100 tropical and sub-tropical countries where malaria is endemic. Nearly 250 million infections and 550,000 deaths occur each year due to malaria worldwide. U.S. travelers and immigrants pose a potential risk to blood donated in the U.S. that can cause transfusion-transmitted malaria.

At present, there is no FDA-approved vaccine against malaria or diagnostic test to detect malaria parasites in blood donors, preventing nearly 100,000 potential blood donors from donating blood based on travel or residence history in endemic countries.

So far scientists have found only a few antigens in the malaria causing parasite, Plasmodium falciparum, that can reproducibly generate transmission-blocking immunity that disrupts the lifecycle of the parasite in mosquitoes and only three vaccine candidates have advanced to clinical testing in humans till date.

In an article titled “Plasmodium falciparum Pf77 and male development gene 1 as vaccine antigens that induce potent transmission-reducing antibodies” published in Science Translational Medicine, scientists report the discovery of two proteins in P. falciparum, that induce naturally-occurring human antibodies in areas where malaria is endemic. The finding bodes well for a sorely-needed transmission-blocking vaccine (TBV) for malaria.

“We applied a transcriptomics-based approach to select P. falciparum genes that are abundantly expressed in the gametocyte stage of the parasite,” the authors note.

Abhai Tripathi, PhD, and his colleagues have identified  Pf77 and PfMDV-1—two parasitic antigens that can disrupt P. falciparum’s life cycle in anopheles mosquitoes and may lead to the development of TBVs. The authors also show immunizing mice with either of the two antigens produces antibodies that block the development of malaria parasites in the guts of female mosquitoes.

To evaluate the suitability of Pf77 and PfMDV as transmission-blocking vaccine candidates, the team follow this up by in-depth studies to characterize the genetic diversity and lifecycle stage-specific expression of these antigens, and the natural immune response mounted against them.

The team observe both antigens are expressed at multiple stages of the parasite’s life cycle and don’t vary substantially across 218 isolates of parasites spanning 4 continents. A majority of serum samples from 100 adults in Ghana harbored antibodies against Pf77 and PfMDV-1, the authors show, suggesting these antigens may help stimulate natural malaria responses in humans.

“Our observations suggest that Pf77 and PfMDV-1 have all the classical characteristics necessary to generate highly potent transmission-reducing antibodies, which can be sustained by natural boosting in endemic regions…These antigens warrant further evaluation as candidate transmission blocking vaccine antigens,” the authors conclude.