Potent immunogenicity of DNA vaccines encoding Plasmodium vivax transmission-blocking vaccine candidates Pvs25 and Pvs28 -: evaluation of homologous and heterologous antigen-delivery prime-boost strategy
Potent immunogenicity of DNA vaccines encoding Plasmodium vivax transmission-blocking vaccine candidates Pvs25 and Pvs28 -: evaluation of homologous and heterologous antigen-delivery prime-boost strategy
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DOI：
10.1016/j.vaccine.2003.11.060
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发表时间：
2004-08-13
期刊：
影响因子：
5.5
通讯作者：
Kumar, N
中科院分区：
文献类型：
--
作者：
Kongkasuriyachai, D;Bartels-Andrews, L;Kumar, N
传播阻断疫苗针对疟疾寄生虫的性阶段，并防止蚊子媒介内的进一步发展，阻止寄生虫的传播。合子/动合子是抑制蚊子中肠中卵囊发育并使蚊子无感染性的抗体的潜在靶标。DNA疫苗构建体表达Pvs 25和Pvs 28（间日疟原虫合子/动合子表面蛋白），其在氨基末端与组织纤溶酶原激活物信号肽融合。用三种剂量免疫后在小鼠中产生的抗体在寄生虫中和在ELISA中识别各自的抗原，并且这些抗体在膜喂养试验中测试时是间日疟原虫传播的有效阻断剂。用Pvs 25和Pvs 28 DNA疫苗构建体的共免疫不影响针对单个抗原的抗原特异性抗体应答，并且抗体在阻断寄生虫传播中保持有效，证明蚊子中肠中卵囊数目减少91-99%。还评价了同源和异源抗原递送初免-加强策略的几种组合，结果表明，通过三种初免-加强策略（DNA初免/DNA加强、DNA初免/蛋白质加强和蛋白质初免/蛋白质加强）的抗体滴度和传播阻断活性相当，与单独的DNA/DNA相比，异源抗原递送初免/加强的免疫原性略好。这些结果证明了编码Pvs 25和Pvs 28的DNA疫苗的有效免疫原性，并保证了在非人灵长类动物中的进一步评价。(C)2004爱思唯尔有限公司保留所有权利。
Transmission-blocking vaccines target the sexual stages of the malaria parasite and prevent further development within the mosquito vector halting the transmission of the parasite. Zygote/ookinetes are potential targets of antibodies inhibiting oocyst development in the mosquito midgut and rendering mosquitoes non-infectious. DNA vaccine constructs were developed expressing Pvs25 and Pvs28 (Plasmodium vivax zygote/ookinete surface proteins) fused at the amino terminus with tissue plasminogen activator signal peptide. Antibodies produced in mice after immunization with three doses recognized respective antigens in the parasites and in an ELISA,and these antibodies when tested in membrane feeding assay were potent blockers of R vivax transmission. Co-immunization with Pvs25 and Pvs28 DNA vaccine constructs did not affect the antigen specific antibody responses against individual antigens, and the antibodies remained effective in blocking parasite transmission demonstrating 91-99% reduction in oocyst number in the mosquito midgut. Several combinations of homologous and heterologous antigen-delivery prime boost strategy were also evaluated and the results suggested that antibody titers and transmission-blocking activities by the three prime-boost strategies (DNA prime/DNA boost, DNA prime/protein boost, and protein prime/protein boost) were comparable with slightly better immunogenicity of heterologous antigen-delivery prime/boost as compared to DNA/DNA alone. These results demonstrate potent immunogenicity of DNA vaccines encoding Pvs25 and Pvs28 and warrant further evaluation in non-human primates. (C) 2004 Elsevier Ltd. All rights reserved.