It is vital that momentum is maintained to ensure the introduction of a highly effective vaccine. many antigens which vary through the entire different levels of its lifestyle routine, and against which sequential consecutive immune system responses are needed. Furthermore, many parasitic protein display high polymorphism, and an individual parasitic clone may possess up to 50 different copies from the gene coding for an important Trofosfamide proteins, expressing a different edition of such proteins in each successive influx of parasitaemia. This specific antigenic variability shows up crucial for the parasite’s success, and clearly is certainly a disadvantage not merely for the contaminated individual also for the researchers aiming to style a vaccine. Trofosfamide Our understanding of the acquired immunity developed against the condition is incomplete and limited. Up to now, no surrogate of immunity continues to be found and there is absolutely no certainty about which particular antigens play an integral role in the introduction of immunity. Furthermore, no appropriate pet model is available and the only way of testing the efficacy of a vaccine depends on logistically complex clinical trials being carried out in malaria endemic areas. The high calculated mean cost of developing a malaria candidate vaccine (around $500 million) and the length of the process before it can be marketed (up to 10C12?years),6 has discouraged pharmaceutical companies from investing in vaccines destined for a market eager for solutions but too poor in resources to pay for them. Is a malaria vaccine feasible? There are four lines of argument supporting the idea that malaria vaccines are feasible. The first argument is based on the naturally acquired immunity that individuals living permanently in endemic areas develop. Partial immunity against the most severe forms of disease7 (death and severe disease) is progressively acquired, followed by immunity against clinical episodes and finally suppression of the parasitaemia to low or undetectable levels.8 Such protection requires a continued booster effect which, however, does not confer sterilising9 immunity, as individuals may become infected although they do not develop clinical symptoms. If such a model could be reproduced by a vaccine, we would be able to confer solid protection against the disease. The second model implies evidence of potential passive immunity against malaria. The administration of purified immunoglobulins from immune malaria patients has been shown to protect patients exposed to the infection.10,11 Moreover, in endemic areas, newborn infants seem to be protected against clinical forms of the disease, a possible consequence of the passive transfer of maternal antimalarial antibodies during pregnancy.12 The third line of argument is supported by experiments carried in the 1970s, during which non\immune volunteers were intensively exposed to UV irradiation\weakened sporozoites. When the volunteers were re\challenged by normally infecting sporozoites, Trofosfamide they had acquired, in up to 90% of cases,13 complete (sterilising) although short\lived immunity. This supports the viability of a vaccine, and should be, despite obvious practical limitations, another model to imitate.14 Recent research using genetically modified parasites (UIS3\deficient) has also shown that this model can be replicated successfully in rodents.15 Finally, several studies16,17 have shown the efficacy of experimental malaria candidate vaccines in humans (adults and children). Nevertheless, despite different candidate vaccines successfully protecting individuals in clinical phase II trials and despite extensive immunological analysis, we still do not know on what immunological basis these individuals are protected, as no clear surrogate measures of immunity have been found. Strategies for vaccine design The ideal malaria vaccine would probably be one that was safe and induced sterilising life\long immunity against infection from childhood. However, this is unlikely in the short term. Given Trofosfamide the lack of surrogate markers of protection and our incomplete understanding of malaria Rabbit Polyclonal to CNTROB immunity, the choice of adequate antigens becomes particularly difficult. It would be reasonable to suppose that antigens should be as conserved as possible, play a vital role in the parasite’s life cycle and be amenable to immune challenge. Moreover, immune responses to that antigen should ideally correlate with a reduced risk of malaria. In the past, there has been a greater emphasis on trying to induce cellular responses together with antibody responses, particularly when targeting the pre\erythrocytic stages.18,19,20 The last few years have highlighted the key role that improved and more potent adjuvants may play..