Malaria transmission blocking vaccines (Ehime University)

Introduction: Highly effective malaria vaccines are essential component toward malaria elimination. Although the leading malaria vaccine, RTS,S/AS01, with modest efficacy is being evaluated in a pilot feasibility trial, development of a malaria transmission-blocking vaccine (TBV) could make a major contribution toward malaria elimination. Only a few TBV antigens have reached pre-clinical or clinical development but with several challenges including difficulties in the expression of malaria recombinant proteins and low immunogenicity in humans. Therefore, novel approaches to accelerate TBV research to preclinical development are critical to generate an efficacious TBV.Areas covered: PubMed was searched to review the progress and future prospects of malaria TBV research and development. We also reviewed registered trials at ClinicalTrials.gov as well as post-genome TBV candidate discovery research including our efforts.Expert opinion: Wheat germ cell-free protein synthesis technology can accelerate TBV development by overcoming some current challenges of TBV research.

Malaria remains one of the most significant infectious diseases worldwide. Concordant with scaled intervention efforts and the emphasis of elimination and eradication on the agenda of many malaria control programs, the development of a malaria vaccine that reduces transmission of the parasite from human host to mosquito vector has been incorporated as an important new strategic goal. Transmission of malaria from man to mosquito relies on gametocytes, highly specialized sexual-stage parasites, that once mature, circulate in the peripheral vasculature of the human host. The complex interplay between mature gametocytes, their uptake in the mosquito bloodmeal and forward maturation/fertilization events provide unique opportunities for intervention. Although recent advances have yielded greater understanding into the mechanisms that mediate sequestration of immature gametocytes in the human host, the spatial dynamics of circulating mature gametocytes in the cutaneous microvaculature remains far less defined, which is the focus of this review.