title: Effect of ingested human antibodies induced by RTS, S/AS01 malaria vaccination in children on Plasmodium falciparum oocyst formation and sporogony in mosquitoes.
abstract: BACKGROUND
  The circumsporozoite protein (CS protein) on the malaria parasites in mosquitoes plays an important role in sporogony in mosquitoes. The RTS,S/AS01 malaria vaccine candidate, which has shown significant efficacy against clinical malaria in a large Phase 3 trial, targets the Plasmodium falciparum CS protein, but the ability of serum from vaccinated individuals to inhibit sporogony in mosquitoes has not been evaluated.
  
  
  METHODS
  Previously a double-blind, randomized trial of RTS,S/AS01 vaccine, as compared with rabies vaccine, in five- to 17-month old children in Tanzania was conducted. In this study, polyclonal human antibodies were purified from the pools of sera taken one month after the third vaccination. IgGs were purified from four pools of sera from 25 RTS,S/AS01 vaccinated children each, and two pools of sera from 25 children vaccinated with rabies vaccine each. The ability of antibodies to inhibit P. falciparum oocyst formation and/or sporogony in the mosquito host was evaluated by a standard membrane-feeding assay. The test antibodies were fed on day 0 (at the same time as the gametocyte feed), or on days 3 or 6 (serial-feed experiments). The oocyst and sporozoite counts were performed on days 8 and 16, respectively. In addition, two human anti-CS monoclonal antibodies (mAb) and a control mAb were also evaluated.
  
  
  RESULTS
  Polyclonal anti-CS IgG preparations from RTS,S-vaccinated children tested at concentrations of 149-210 ELISA units (EU)/ml did not show significant inhibition in oocyst and sporozoite formation when the antibodies were fed with gametocytes at the same time, or later (serial-feed experiments). Similarly, anti-CS mAbs tested at 6,421 or 7,122 EU/ml did not show reduction in oocyst and sporozoite formation.
  
  
  CONCLUSIONS
  This study does not support the concept that anti-CS antibodies induced by the RTS,S/AS01 vaccines in humans noticeably reduce malaria transmission by blocking P. falciparum sporozoite development or salivary gland invasion in mosquitoes when taken up during feeding.
authors.affiliation: Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 12735 Twinbrook Parkway, Rockville, MD 20852, USA. kmiura@niaid.nih.gov.
authors.forename: Kazutoyo
authors.initials: K
authors.lastname: Miura
authors.forename: Erik
authors.initials: E
authors.lastname: Jongert
authors.forename: Bingbing
authors.initials: B
authors.lastname: Deng
authors.forename: Luwen
authors.initials: L
authors.lastname: Zhou
authors.forename: John P
authors.initials: JP
authors.lastname: Lusingu
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Drakeley
authors.forename: Michael P
authors.initials: MP
authors.lastname: Fay
authors.forename: Carole A
authors.initials: CA
authors.lastname: Long
authors.forename: Johan
authors.initials: J
authors.lastname: Vekemans
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology*; D001769:Blood / Q000276:immunology; D009033:Culicidae / Q000187:drug effects / Q000469:parasitology*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007223:Infant; D017780:Malaria Vaccines / Q000276:immunology*; D008297:Male; D059208:Parasite Load; D010963:Plasmodium falciparum / Q000187:drug effects / Q000254:growth & development* / Q000276:immunology*; D016032:Randomized Controlled Trials as Topic; D033761:Spores, Protozoan / Q000187:drug effects / Q000254:growth & development* / Q000276:immunology*; D013636:Tanzania; D014614:Vaccines, Synthetic / Q000276:immunology*
chemical_list: D000913:Antibodies, Protozoan; D007074:Immunoglobulin G; D017780:Malaria Vaccines; C577001:RTS,S-AS01 vaccine; D014614:Vaccines, Synthetic