Kim Young Chan, Dema Barbara, Rodriguez-Garcia Roberto, López-Camacho César, Leoratti Fabiana M S, Lall Amar, Remarque Edmond J, Kocken Clemens H M, Reyes-Sandoval Arturo
The Jenner Institute, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7DQ, UK.
Department of Parasitology, Biomedical Primate Research Centre (BPRC), 2288 GJ Rijswijk, The Netherlands.
Vaccines (Basel). 2020 Jul 6;8(3):363. doi: 10.3390/vaccines8030363.
is the world's most widely distributed human malaria parasite, with over 2.8 billion people at risk in Asia, the Americas, and Africa. The 80-90% new malaria infections are due to relapses which suggest that a vaccine with high efficacy against relapses by prevention of hypnozoite formation could lead to a significant reduction in the prevalence of infections. Here, we describe the development of new recombinant ChAdOx1 and MVA vectors expressing Thrombospondin Related Adhesive Protein (PcTRAP) and the circumsporozoite protein (PcCSP). Both were shown to be immunogenic in mice prior to their assessment in rhesus macaques. We confirmed good vaccine-induced humoral and cellular responses after prime-boost vaccination in rhesus macaques prior to sporozoite challenge. Results indicate that there were no significant differences between mock-control and vaccinated animals after challenge, in terms of protective efficacy measured as the time taken to 1st patency, or as number of relapses. This suggests that under the conditions tested, the vaccination with PcTRAP and PcCSP using ChAdOx1 or MVA vaccine platforms do not protect against pre-erythrocytic malaria or relapses despite good immunogenicity induced by the viral-vectored vaccines.
是世界上分布最广泛的人类疟原虫,在亚洲、美洲和非洲有超过28亿人面临感染风险。80%-90%的新发疟疾感染是由复发引起的,这表明一种通过预防休眠子形成而对复发具有高效力的疫苗可能会显著降低感染率。在此,我们描述了表达血小板反应蛋白相关粘附蛋白(PcTRAP)和环子孢子蛋白(PcCSP)的新型重组ChAdOx1和MVA载体的研发情况。在恒河猴中进行评估之前,二者在小鼠体内均显示出免疫原性。在子孢子攻击之前,我们在恒河猴中进行初免-加强免疫接种后确认了良好的疫苗诱导的体液和细胞反应。结果表明,在攻击后,以首次出现虫血症的时间或复发次数衡量的保护效力方面,模拟对照动物和接种疫苗的动物之间没有显著差异。这表明,在所测试的条件下,尽管病毒载体疫苗诱导了良好的免疫原性,但使用ChAdOx1或MVA疫苗平台接种PcTRAP和PcCSP并不能预防红细胞前期疟疾或复发。