Plasmodium proteases and their role in development of Malaria vaccines

Adv Parasitol. 2024:126:253-273. doi: 10.1016/bs.apar.2024.08.001. Epub 2024 Sep 25.

Abstract

Malaria remains a major health hazard for humans, despite the availability of efficacious antimalarial drugs and other interventions. Given that the disease is often deadly for children under 5 years and pregnant women living in malaria-endemic areas, an efficacious vaccine to prevent transmission and clinical disease would be ideal. Plasmodium, the causative agent of malaria, uses proteases and protease inhibitors to control and process to invade host, modulate host immunity, and for pathogenesis. Plasmodium parasites rely on these proteases for their development and survival, including feeding their metabolic needs and invasion of both mosquito and human tissues, and have thus been explored as potential targets for prophylaxis. In this chapter, we have discussed the potential of proteases like ROM4, SUB2, SERA4, SERA5, and others as vaccine candidates. We have also discussed the role of some protease inhibitors of plasmodium and mosquito origin. Inhibition of plasmodium proteases can interrupt the parasite development at many different stages therefore understanding their function is key to developing new drugs and malaria vaccines.

Keywords: Antimalarial drugs; Plasmodium; Protease inhibitors; Proteases; Serpins; Vaccine development; Vaccines; Vector-borne pathogens.

MeSH terms

  • Animals
  • Humans
  • Malaria / drug therapy
  • Malaria / immunology
  • Malaria / parasitology
  • Malaria / prevention & control
  • Malaria Vaccines* / immunology
  • Peptide Hydrolases* / immunology
  • Plasmodium* / drug effects
  • Plasmodium* / enzymology
  • Plasmodium* / immunology
  • Plasmodium* / physiology
  • Protease Inhibitors / pharmacology
  • Protease Inhibitors / therapeutic use
  • Protozoan Proteins* / antagonists & inhibitors
  • Protozoan Proteins* / immunology
  • Vaccine Development

Substances

  • Malaria Vaccines
  • Peptide Hydrolases
  • Protease Inhibitors
  • Protozoan Proteins