Antimalarial Vaccines - A multilateral effort known as the Multi-Stage DNA-based Malaria Vaccine Operation (MuStDO) has been launched to develop DNA vaccines against Plasmodium falciparum (21). These vaccines are to be targeted against the pre-erythrocytic and erythrocytic forms of P. falciparum, and are intended to protect travelers and short term residents of high risk areas, as well as reduce morbidity in endemic populations. Vaccines targeted against 5 genes that encode for pre-erythrocytic form antigens (termed MuStDO 5) will neutralize sporozoite and early liver stage parasites, while vaccines targeting 10 additional genes (MuStDO 10) are designed to produce immune responses against merozoites and infected erythrocytes. Other targets for and approaches to the development of a suitable antimalarial vaccine have recently been reviewed (22). Proposed targets include antibodies to antigens expressed in the sporozoite stage (blocking invasion of hepatocytes) and the merozoite stage (blocking invasion of the red blood cell), as well as against toxins produced by Plasmodium that produce clinical disease and severe malaria. One such malarial toxin, a glycophosphatidylinositol-based hexasaccharide, has recently been synthesized using a solid phase method, and is being used for vaccine development (23). Genes for the potential transmission-blocking antigens Pvs25 and Pvs28 from P. vivax have been cloned and expressed in yeast,, and then used to generate antibodies in mice (24). These antibodies completely prevented transmission of P. vivax from infected sera, and have led to clinical trials, as well as extension of the work to the Pfs25 P. falciparum ortholog. Other antimalarial vaccines are currently in phase 1 and 2 clinical trials, including the RTS/S/AS02 antisporozoite antibody, and a series of DNA and recombinant viral vaccine products (25).
Synthetic Analogues Related to Quinine and Chloroauine - The cinchona alkaloid quinine, 2, was the first compound to exhibit significant antimalarial activity. Subsequent studies produced the synthetic analogue chloroquine, 3, which was initially an excellent treatment for malaria. However, the evolution of chloroquine-resistant strains of P. falciparum have rendered this drug virtually useless in certain
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