a viral vectored prime-boost immunization regime targeting the malaria pfs25 antigen induces transmission-blocking activity病毒载体启动u2014提高免疫机制针对疟疾pfs25抗原诱导阻断传播活动.pdfVIP

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2017-09-07 发布于上海
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a viral vectored prime-boost immunization regime targeting the malaria pfs25 antigen induces transmission-blocking activity病毒载体启动u2014提高免疫机制针对疟疾pfs25抗原诱导阻断传播活动.pdf

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a viral vectored prime-boost immunization regime targeting the malaria pfs25 antigen induces transmission-blocking activity病毒载体启动u2014提高免疫机制针对疟疾pfs25抗原诱导阻断传播活动

A Viral Vectored Prime-Boost Immunization Regime Targeting the Malaria Pfs25 Antigen Induces Transmission-Blocking Activity 1 2 1 3 1 Anna L. Goodman *, Andrew M. Blagborough , Sumi Biswas , Yimin Wu , Adrian V. Hill , Robert E. Sinden1,2, Simon J. Draper 1 1The Jenner Institute, University of Oxford, Oxford, United Kingdom, 2 Division of Cell and Molecular Biology, Imperial College London, London, United Kingdom, 3 Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, Rockville, Maryland, United States of America Abstract The ookinete surface protein Pfs25 is a macrogamete-to-ookinete/ookinete stage antigen of Plasmodium falciparum, capable of exerting high-level anti-malarial transmission-blocking activity following immunization with recombinant protein-in-adjuvant formulations. Here, this antigen was expressed in recombinant chimpanzee adenovirus 63 (ChAd63), human adenovirus serotype 5 (AdHu5) and modified vaccinia virus Ankara (MVA) viral vectored vaccines. Two immunizations were administered to mice in a heterologous prime-boost regime. Immunization of mice with AdHu5 Pfs25 at week 0 and MVA Pfs25 at week 10 (Ad-MVA Pfs25) resulted in high anti-Pfs25 IgG titers, consisting of predominantly isotypes IgG1 and IgG2a. A single priming immunization with ChAd63 Pfs25 was as effective as AdHu5 Pfs25 with respect to ELISA titers at 8 weeks post-immunization. Sera from Ad-MVA Pfs25 immunized mice inhibited the transmission of P. falciparum to the mosquito both ex vivo and in vivo. In a standard membrane-feeding assay using NF54 strain P. falciparum,