Malaria Vaccination-is it Possible ?

Human malaria is, among animal and human parasite protozoan diseases, the one for which,The most intense effort of research has been accumulated in the last decades in view of the development of vaccines. Scientific literature on this topic accounts for thousands of references every year, particularly concerning falciparum malaria. This is comprehensible because of the importance of malaria as a leading cause of morbidity and mortality in the tropical areas of the world, with an estimated 300±500 million cases each year and more than 1 million deaths, mainly among children below five years of age in Africa. A naturally acquired immunity against malaria is observed in endemic areas where people are exposedto frequent infections. This immunity develops slowly and is characterized, in a first step,by the acquisition of clinical resistance to symptoms, clinical immunity, and later by the ability to control parasitemia at a low level, antiparasite immunity, usually fully expressed only in adults. Classical experiments of British immunologists working in Africa showed in the 60s that the natural immunity was antibody-dependent, directed against the asexual blood stages of the parasite.More recently, sero-epidemiological surveys in endemic areas have shown the existence of anti-sporozoite specific antibodies as well as antibodies and CTL cells directed against antigens of the hepatic stage. Finally, naturally and artificially raised antibodies against the gametocytes and latter forms of the sexual stage have been described as able to block the development of the parasite in the mosquito. These observations indicate that immunity in malaria is stage specific and this was indeed proved in laboratory experiments with rodent and primate models. Thus, efforts in the construction of vaccines have been directed towards different target alternatives. The starting point was the impossibility of raising vaccines from parasite materials since no culture systems are available for pre-erythrocytic stages of the parasites while culture of blood stages (P. falciparum) require growth in human red cells. These constraints made malaria vaccines one of the first domains of medical sciences in which nascent genetic engineering technology was actively introduced with the aim of preparing sub-unit vaccines. In principle the ideal target would be the pre-erythrocyte stages antigens (sporozoites and hepatic forms) since an effective vaccine against these stages would block transmission. However, an inconvenience of such a vaccine is that it would need to induce sterile immunity, because a surviving sporozoite or hepatic schizont would be sufficient to produce erythrocyte invasion and multiplication of the parasite in the blood. Sterile immunity against blood stage, however,is not naturally observed in humans of endemic areas and is usually not experimentally obtained in animal models. In contrast, non sterilizing, partially active vaccines against asexual blood stages would be favorable to avoid the development of high parasitemia and presumably reduce severe malaria outcome responsible for mortality.However, it would poorly interfere at the level of sources of infection in an endemic area and, therefore, in the level of transmission. Anti sexual stage vaccines transmission blocking vaccines would abolish or reduce transmission but would not protect the vaccinated individual from infection (altruistic vaccine). In conclusion, these considerations point to the interest in developping multigene, multi-stage vaccination approach like the CDC/NIIMALVAC-1, for which preliminary assays are now in course.