Effect of ingested human antibodies induced by RTS, S/AS01 malaria vaccination in children on Plasmodium falciparum oocyst formation and sporogony in mosquitoes
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- 作者：Kazutoyo Miura (5)
Erik Jongert (6)
Bingbing Deng (5)
Luwen Zhou (5)
John P Lusingu (7) (8)
Chris J Drakeley (9)
Michael P Fay (10)
Carole A Long (5)
Johan Vekemans (6)
5. Laboratory of Malaria and Vector Research ; National Institute of Allergy and Infectious Diseases ; National Institutes of Health ; 12735 Twinbrook Parkway ; Rockville ; MD ; 20852 ; USA
6. GlaxoSmithKline Vaccines ; Wavre ; Belgium
7. National Institute for Medical Research ; Tanga Centre ; Korogwe site ; Tanga ; Tanzania
8. Center for Medical Parasitology ; Department of Medical Microbiology and Immunology ; University of Copenhagen ; Copenhagen ; Denmark
9. Faculty of Infectious and Tropical Diseases ; London School of Hygiene and Tropical Medicine ; London ; UK
10. Biostatistics Research Branch ; National Institute of Allergy and Infectious Diseases ; National Institutes of Health ; Bethesda ; USA - 关键词：RTS ; S/AS01 ; Oocyst formation ; Sporogony ; Standard membrane feeding assay
- 刊名：Malaria Journal
- 出版年：2014
- 出版时间：December 2014
- 年：2014
- 卷：13
- 期：1
- 全文大小：293 KB
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- 出版者：BioMed Central
- ISSN：1475-2875
文摘
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.