Current Research Goals
The ideal vaccine would be cheap, extremely safe, induce life-long immunity, be active against all strains of the parasite and result in nearly complete interruption of the malaria life cycle by vaccine-induced immune responses. Unfortunately, the prospects of developing such a malaria vaccine remain elusive.
Current strategies of malaria vaccine development are focusing on the more modest goal of reducing the risk of infection, thereby preventing or reducing merozoite release from the liver, controlling the erythrocytic merozoite reproduction cycle or reducing gamete production to reduce malaria transmission. Vaccine development efforts against pre-erythrocytic and erythrocytic stages have focused on strategies aiming at a 50% or more reduction in severe disease. Levels of efficacy of this magnitude are considered by several public-health authorities as worth large-scale implementation in malaria control programs.[8]
Important preclinical research priorities include antigen and adjuvant discovery, delivery platform optimization and whole cell vaccine attenuation. Once in clinical testing, vaccine candidates must demonstrate safety and efficacy. High standards of care are required to enable the demonstration of vaccine safety and appropriately diagnose a complex disease, such as severe malaria.[9] Support is essential for Good Clinical and Laboratory Practice implementation, in order to achieve a level acceptable to supervising regulatory authorities. Improved infrastructure and patient management must benefit not only clinical trial participants but also other members of the communities in order to ensure that study participation is not perceived as being coercive.
Another area of important current malaria research is the definition of correlates of vaccine-induced protection. Such a correlate would facilitate vaccine development efforts, allowing studies of relevant immunological readouts rather than clinical or parasitological end points. Efforts toward the characterization of protective immunological responses demonstrated the important role of both humoral and T-cell responses in pre-erythrocytic models as well as in the blood stage.[10,11] Sero-epidemiologic surveys have contributed to the identification of several candidate antigens, including merozoite surface protein (MSP)1, MSP3, apical membrane antigen (AMA)1 and liver-stage antigen (LSA)1 as potential targets of protective immunity for vaccine development, but the relevance of individual immune markers of protection in vaccine studies has yet to be demonstrated. In vitro assays to measure the inhibitory effect of antibodies on sporozoite infectivity or on penetration and development in erythrocytes - the growth inhibition assay (GIA) - have been developed,[12,13,14] and may prove to be useful in the future. However, GIAs are complex and their advantages over clinical readouts are yet to be confirmed. Results from clinical trials have, so far, failed at identifying clear immunological correlates of protection.[15]
Expert Rev Vaccines. 2008;7(2):223-240. © 2008 Future Drugs Ltd.
Cite this: Plasmodium falciparum Malaria Vaccines in Development - Medscape - Feb 01, 2008.
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