title: Transmission blocking malaria vaccines: Assays and candidates in clinical development.
abstract: Stimulated by recent advances in malaria control and increased funding, the elimination of malaria is now considered to be an attainable goal for an increasing number of malaria-endemic regions. This has boosted the interest in transmission-reducing interventions including vaccines that target sexual, sporogenic, and/or mosquito-stage antigens to interrupt malaria transmission (SSM-VIMT). SSM-VIMT aim to prevent human malaria infection in vaccinated communities by inhibiting parasite development within the mosquito after a blood meal taken from a gametocyte carrier. Only a handful of target antigens are in clinical development and progress has been slow over the years. Major stumbling blocks include (i) the expression of appropriately folded target proteins and their downstream purification, (ii) insufficient induction of sustained functional blocking antibody titers by candidate vaccines in humans, and (iii) validation of a number of (bio)-assays as correlate for blocking activity in the field. Here we discuss clinical manufacturing and testing of current SSM-VIMT candidates and the latest bio-assay development for clinical evaluation. New testing strategies are discussed that may accelerate the evaluation and application of SSM-VIMT.
authors.affiliation: Department of Medical Microbiology, Radboud University Medical Center, PO Box 9101 (268), Geert Grooteplein 28, 6500 HB Nijmegen, The Netherlands. Electronic address: Robert.Sauerwein@radboudumc.nl.
authors.forename: R W
authors.initials: RW
authors.lastname: Sauerwein
authors.affiliation: Department of Medical Microbiology, Radboud University Medical Center, PO Box 9101 (268), Geert Grooteplein 28, 6500 HB Nijmegen, The Netherlands.
authors.forename: T
authors.initials: T
authors.lastname: Bousema
mesh_terms: D000818:Animals; D000852:Anopheles / Q000469:parasitology; D000913:Antibodies, Protozoan / Q000097:blood / Q000276:immunology; D000953:Antigens, Protozoan / Q000276:immunology; D000954:Antigens, Surface / Q000276:immunology; D001681:Biological Assay; D002986:Clinical Trials as Topic; D060740:Disease Eradication; D006801:Humans; D007303:Insect Vectors / Q000469:parasitology; D008288:Malaria / Q000276:immunology / Q000517:prevention & control* / Q000635:transmission*; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000276:immunology*; D016778:Malaria, Falciparum / Q000276:immunology / Q000517:prevention & control / Q000635:transmission; D016780:Malaria, Vivax / Q000517:prevention & control / Q000635:transmission; D010963:Plasmodium falciparum / Q000276:immunology; D010966:Plasmodium vivax / Q000276:immunology*
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D000954:Antigens, Surface; D017780:Malaria Vaccines
keywords: Anopheles; Elimination; Gamete; Gametocyte; Malaria; Transmission