原创力文档a malaria vaccine based on the polymorphic block 2 region of msp-1 that elicits a broad serotype-spanning immune response疟疾疫苗的基础上多态块2地区引发广泛的msp-1 serotype-spanning免疫反应.pdfVIP
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a malaria vaccine based on the polymorphic block 2 region of msp-1 that elicits a broad serotype-spanning immune response疟疾疫苗的基础上多态块2地区引发广泛的msp-1 serotype-spanning免疫反应
A Malaria Vaccine Based on the Polymorphic Block 2
Region of MSP-1 that Elicits a Broad Serotype-Spanning
Immune Response
1 1 1 2
Graeme J. M. Cowan , Alison M. Creasey , Kelwalin Dhanasarnsombut , Alan W. Thomas , Edmond J.
2 1
Remarque , David R. Cavanagh *
1 Institute of Immunology and Infection Research, University of Edinburgh, Edinburgh, United Kingdom, 2 Biomedical Primate Research Center, Rijswijk, The Netherlands
Abstract
Polymorphic parasite antigens are known targets of protective immunity to malaria, but this antigenic variation poses
challenges to vaccine development. A synthetic MSP-1 Block 2 construct, based on all polymorphic variants found in natural
Plasmodium falciparum isolates has been designed, combined with the relatively conserved Block 1 sequence of MSP-1 and
expressed in E.coli. The MSP-1 Hybrid antigen has been produced with high yield by fed-batch fermentation and purified
without the aid of affinity tags resulting in a pure and extremely thermostable antigen preparation. MSP-1 hybrid is
immunogenic in experimental animals using adjuvants suitable for human use, eliciting antibodies against epitopes from all
three Block 2 serotypes. Human serum antibodies from Africans naturally exposed to malaria reacted to the MSP-1 hybrid as
strongly as, or better than the same serum reactivities to individual MSP-1 Block 2 antigens, and these antibody responses
showed clear associations with reduced incidence of malaria episodes. The MSP-1 hybrid is designed to induce a protective
antibody response to the highly polymorphic Block 2 region of MSP-1, enhancing the repertoire of MSP-1 Block 2 antibody
responses fo
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