A Research and Development In Malarial Vaccine: Systems of Genetically-Based Resistance to Malaria |
More than 30years after the first report of successfulvaccination against malaria using radiation-attenuated sporozoites, aneffective malaria vaccine is not yet available. However, field and experimentaldata indicate that it can be developed. An astonishing amount of data hasaccumulated concerning parasite biology, host-parasite interactions, immunityand escape mechanisms, targets and modulators of immune responses.Nevertheless, so far this knowledge has not been enough to make us understandhow to properly manipulate the whole system to build an effective vaccine. Inthis article, we describe candidate antigens, mechanisms, targets and trialsperformed with potential malaria vaccines and discuss the approaches, in vivoand in vitro models, constraints and how technologies such as DNA vaccination, genomics/proteomics and reverse immunogeneticsare providing exciting results and opening new doors to make malaria vaccine areality. Malaria remains one of the most prevalent parasitizesworldwide. About 350 to 500 million febrile episodes are observed yearly inAfrican children alone and more than 1 million people die because of malariaeach year. Multiple factors have hampered the effective control of thisdisease, some of which include the complex biology of the Plasmodium parasites,their high polymorphism and their increasingly high resistance to antimalarialdrugs, mainly in endemic regions. The ancient interaction between malarialparasites and humans has led to the fixation in the population of severalinherited alterations conferring protection against malaria. Some of themechanisms underlying protection against this disease are described in thisreview for hemoglobin-inherited disorders (thalassemia, sickle-cell trait, HbCand HbE), erythrocyte polymorphisms (ovalocytosis and Duffy blood group),enzymopathies (G6PD deficiency and PK deficiency) and immunogenetics variants(HLA alleles, complement receptor 1, NOS2, tumor necrosis factor-α promoter andchromosome 5q31–q33 polymorphisms). Malaria, a vector-borne infectious disease, is currentlya grave and universal concern with a significant social, economic, and humancost, mainly in developing countries. In addition, the emergence and spread ofresistance to antimalarial therapies have further aggravated the globalsituation. Currently most of the research is focused on development ofantimalarial drugs, drug resistance, and novel formulations to maximize thetherapeutic effect. A number of novel molecules potentially active againstmalarial parasites are being developed. A vaccine is still viewed as a criticalpart of a long-term malaria control strategy. In the last several years variousstudies have shown significant progress in the development of vaccines againstmalaria. Advancement in vaccine technology and immunology is being used todevelop malaria subunit vaccines that would open up new vistas for effectivetreatment and control of malaria. The development of an effective malaria vaccinerepresents one of the most important approaches that would provide acost-effective intervention in addition to currently available malaria controlstrategies. An overview on progress in antimalarial vaccines is presented.