Malaria has been a scourge for humanity through centuries and is still one of the most fatal infectious diseases on earth. Although the causal organism for malaria, Plasmodium spp, was discovered in 19^th century, we are yet to develop a vaccine against malaria. This could be attributed to the difficulty in manipulation of Plasmodium but also lack of funding for infectious disease not prevalent in industrialized nations of Europe or United States.

            Plasmodium has a huge arsenal of strategies up its sleeve or pseudopodium for its survival, proliferation and transmission. This protozoan can be transmitted in the sporozoite stage from mosquito to human blood where it goes through a short hepatic (liver) and a much longer erythrocytic (blood) phase. It also produces a smaller number of male and female gametocytes in the blood which are taken up by mosquitoes. Gametes fuse to form zygotes and then differentiate into sporozoites in the mosquito gut which can be transmitted again through a mosquito bite (Figure 1). The blood phase causes most of the symptoms and morbidity associated with malaria  (cerebral malaria in case of P. faciparum due aggregation and rosetting of infected cells in the brain vasculature).  Plasmodium protects itself form host immune response by avoiding/restricting passage through the peripheral blood and  lymph nodes as well as by antigen (e.g. PfEMP1) switching on the surface of infected cells. Over the last few decades, attempts have been made to design vaccines against antigens from all or one stage in Plasmodium life cycle but of no avail.

            A recent study by Algae researchers at South Western Medical Center, Texas may just bring the elusive malaria vaccine one step closer. A gamete specific protein called HAP2 was found to essential for fertilization in green alga Chlamydomonas. HAP2 homologs were found in the genomes of many plants and protozoa including Plasmodium and Leishmania. The resulting collaboration with malaria researchers at the Imperial College, London and UC, Irvine led to the study published in Genes & Dev. It shows that HAP2 is also essential for zygote formation in Plasmodium and lack of HAP2 leads to block on malaria transmission through mosquitoes in a mouse model of malaria. Gametocyes lacking HAP2 fail to form zygotes and sporozoites in the mosquito gut and these mosquitoes failed to transmit malaria.

            HAP2 appears to be a good “transmission blocking vaccine” candidate. A person exposed to such a vaccine would have anti-HAP2 antibody but he would get malaria when bitten by a mosquito carrying Plasmodium sporozoites. When bitten again, the mosquito would take both plasmodium gametocytes as well as anti-HAP2 antibody in its blood meal. The gametes would fail to fertilize in the mosquito gut in presence of HAP2 antibody and this mosquito would fail to transmit malaria in its subsequent blood meals (Figure 2).  We have to wait and see if HAP2 would be used in the fight against malaria and possibly Leishmaniasis.