Background Plasmodium falciparum and P. vivax account for >90% global malaria burden. Transmission intervention strategies encompassing transmission-blocking vaccines (TBV) and drugs represent ideal public health tools to eliminate malaria at the population level. The availability of mature P. falciparum gametocytes through in vitro culture has facilitated development of a standard membrane feeding assay (SMFA) to assess efficacy of transmission interventions against P. falciparum. The lack of in vitro culture for P. vivax has significantly hampered similar progress on P. vivax and limited studies have been possible using blood from infected patients in endemic areas. The ethical and logistical limitations of on-time access to blood from patients have impeded the development of P. vivax TBVs. Methods Transgenic murine malaria parasites (P. berghei) expressing TBV candidates offer a promising alternative for evaluation of P. vivax TBVs through in vivo studies in mice, and ex vivo membrane feeding assay (MFA). Results We describe the development of transmission competent transgenic TgPbvs25 parasites and optimization of parameters to establish an ex vivo MFA to evaluate P. vivax TBV based on Pvs25 antigen. Conclusions The MFA is expected to expedite Pvs25-based TBV development without dependence on blood from P. vivax-infected patients in endemic areas for evaluation.

中文翻译：

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使用 Pvs25 转基因伯氏疟原虫评估间日疟原虫传播阻断疫苗功能有效性的新型离体测定

背景 恶性疟原​​虫和间日疟原虫占全球疟疾负担的90％以上。包括阻断传播疫苗（TBV）和药物在内的传播干预策略是在人口层面消除疟疾的理想公共卫生工具。通过体外培养获得成熟的恶性疟原虫配子细胞促进了标准膜喂养试验（SMFA）的开发，以评估针对恶性疟原虫传播干预措施的功效。间日疟原虫体外培养的缺乏极大地阻碍了间日疟原虫的类似进展，并且利用来自流行地区感染患者的血液进行的研究有限。按时获取患者血液的伦理和后勤限制阻碍了间日疟原虫 TBV 的发展。方法 表达 TBV 候选物的转基因鼠疟疾寄生虫 (P. berghei) 为通过小鼠体内研究和离体膜喂养测定 (MFA) 评估间日疟原虫 TBV 提供了一种有前途的替代方案。结果我们描述了具有传播能力的转基因TgPbvs25寄生虫的开发以及参数的优化以建立离体MFA以评估基于Pvs25抗原的间日疟原虫TBV。结论 MFA 有望加速基于 Pvs25 的 TBV 发展，而不依赖于流行地区间日疟原虫感染患者的血液进行评估。