title: Preerythrocytic malaria vaccine development.
abstract: OBJECTIVE
  This review examines the potential of current preerythrocytic stage malaria vaccine approaches to reduce the global burden of malaria.
  
  
  RESULTS
  Radiation-attenuated parasite vaccines induce lasting sterile protection in all models tested. Inherent safety concerns in conjunction with challenges to produce and deliver a radiation-attenuated parasite vaccine have prevented its mass production and application. Recent advances in genetic engineering and initiatives in production process development of live attenuated malaria vaccines, however, will overcome roadblocks that currently prevent their large-scale application. Development of preerythrocytic subunit vaccines has focused on the circumsporozoite protein and the thrombospondin related anonymous protein, yet the most advanced circumsporozoite protein-based vaccine confers limited protection against infection in malaria endemic areas. Work in rodent malaria models demonstrated that circumsporozoite protein-based immunity is not required for to achieve sterile protection.
  
  
  CONCLUSIONS
  We conclude that preerythrocytic malaria vaccine efforts should focus on two major areas: development of a safe live attenuated sporozoite vaccine with its accelerated testing in malaria endemic areas and identification of as yet unknown antigens that reproduce sterilizing immune responses induced by vaccination with whole parasites. The sporozoite challenge model provides a unique opportunity to rapidly test preerythrocytic vaccine candidates.
authors.affiliation: Seattle Biomedical Research Institute, Seattle, Washington 98109-5219, USA.
authors.forename: Sebastian A
authors.initials: SA
authors.lastname: Mikolajczak
authors.forename: Ahmed S I
authors.initials: AS
authors.lastname: Aly
authors.forename: Stefan H I
authors.initials: SH
authors.lastname: Kappe
mesh_terms: D000818:Animals; D000953:Antigens, Protozoan / Q000097:blood / Q000276:immunology; D006801:Humans; D008288:Malaria / Q000469:parasitology / Q000517:prevention & control*; D017780:Malaria Vaccines / Q000276:immunology*; D010961:Plasmodium / Q000254:growth & development / Q000276:immunology; D034101:Sporozoites / Q000276:immunology; D014613:Vaccines, Attenuated / Q000276:immunology; D022223:Vaccines, Subunit / Q000276:immunology
chemical_list: D000953:Antigens, Protozoan; D017780:Malaria Vaccines; D014613:Vaccines, Attenuated; D022223:Vaccines, Subunit