Development of a novel malarial vaccine design: a hypothetical approach

Curr Drug Discov Technol. 2014;11(4):239-42. doi: 10.2174/1570163811666141106102325.

Abstract

P. falciparum is highly virulent in nature because of its ability to modify the infected host red blood cells, adherence to the vascular endothelium and changes in antigenicity at different stages. Also slow migration time in the dermal and endothelial cells leads to decreased immune response. To overcome the problems, there is a need to design a vaccine which increases the migration time of the parasite, enhances the immune response, enables recognition of surface antigens and causes minimal clinical infection as a side-effect. An ITI-based (Infection-Treatment Immunization) vaccine development strategy is to be adopted to develop this novel vaccine. This will include administration of a liquid solution of purified, non-attenuated sporozoites from an infected female Anopheles mosquito, AS02A adjuvant and chlorate (a metabolic inhibitor of sulfation that decreases the extent of GAG sulfation). To control infection, a drug-cover of artemisinin will be administered as a part of the vaccination strategy along with a specific protease inhibitor MRT12113 which prevents RBC rupture and reinvasion by the parasite. This vaccine will intend to increase the overall migration time of the parasite in blood which is otherwise approximately 30 minutes, resulting in an overall enhanced immune response. It also intends to reduce parasite invasion in cells and their consequent rupture thus preventing the clinical condition-malaria.

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Animals
  • Artemisinins / administration & dosage
  • Artemisinins / pharmacology
  • Benzopyrans / administration & dosage*
  • Benzopyrans / pharmacology
  • Catechols / administration & dosage*
  • Catechols / pharmacology
  • Cell Movement / drug effects
  • Chlorates / administration & dosage
  • Chlorates / pharmacology
  • Drug Design*
  • Drug Therapy, Combination / methods*
  • Female
  • Humans
  • Immunotherapy, Active / methods*
  • Malaria Vaccines* / administration & dosage
  • Malaria, Falciparum / drug therapy*
  • Malaria, Falciparum / parasitology
  • Plasmodium falciparum / drug effects
  • Plasmodium falciparum / pathogenicity
  • Protease Inhibitors / administration & dosage
  • Protease Inhibitors / pharmacology
  • Sporozoites

Substances

  • Adjuvants, Immunologic
  • Artemisinins
  • Benzopyrans
  • Catechols
  • Chlorates
  • MRT12113
  • Malaria Vaccines
  • Protease Inhibitors
  • artemisinin