Plant-produced recombinant transmission blocking vaccine candidates to combat malaria

Malaria is one of the world's most devastating infectious diseases, resulting in over half a million deaths annually. No licensed vaccine is currently available, although the pre-erythrocytic vaccine RTS,S is in advanced stage clinical trials and significantly reduces cases of malaria. However, RTS,S alone will be insufficient to eradicate malaria and, consequently, a variety of other vaccines targeting erythrocytic and sexual stages of the parasite's life cycle are under development. The latter comprise transmission blocking vaccines (TBVs) that elicit antibodies against surface proteins of the parasite's sexual stages and so prevent sexual development and transmission. Therefore, the World Health Organization has proposed TBVs as an effective means to reduce malaria transmission and serve as a key element in potentially eradicating the disease. Several TBV candidates are under development, including subunit vaccines based on the gametocyte and gamete antigens P4 8/45 and P230 and the zygote and ookinete antigens P25 and P28. These antigens have proven challenging to produce in established recombinant systems, potentially in part due to the large number of disulfide bonds. However, recently, plant-based platforms have been recruited for the production of these challenging antigens. Recombinant plants have several advantages for the production of subunit vaccines and therapeutic proteins, including cost-effectiveness, scalability, lack of harbored mammalian pathogens, and possession of the machinery for eukaryotic posttranslational protein modifications. Here, we review ongoing efforts to produce TBV candidates in plant-based expression systems.