Francian Alexandra, Flores-Garcia Yevel, Powell John R, Petrovsky Nikolai, Zavala Fidel, Chackerian Bryce
bioRxiv. 2024 Sep 7:2024.09.05.611467. doi: 10.1101/2024.09.05.611467.
Malaria is a highly lethal infectious disease caused by parasites. These parasites are transmitted to vertebrate hosts when mosquitoes of the genus probe for a blood meal. Sporozoites, the infectious stage of , transit to the liver within hours of injection into the dermis. Vaccine efforts are hindered by the complexity of the parasite's lifecycle and the speed at which the infection is established in the liver. In an effort to enhance immunity against , we produced a virus-like particle (VLP)-based vaccine displaying an epitope of TRIO, an salivary protein which has been shown to enhance mobility and dispersal of sporozoites in the dermis. Previous work demonstrated that passive immunization with TRIO offered protection from liver infection and acted synergistically with a targeted vaccine. Immunization of mice with TRIO VLPs resulted in high-titer and long-lasting antibody responses that did not significantly drop for over 18 months post-immunization. TRIO VLPs were similarly immunogenic when combined with an anti-malaria vaccine targeting the L9 epitope of the circumsporozoite protein.However, when used in a malaria challenge mouse model, TRIO VLPs only provided modest protection from infection and did not boost the protection provided by L9 VLPs.
疟疾是一种由寄生虫引起的高致死性传染病。当按蚊属蚊子为获取血餐而叮咬时,这些寄生虫会传播给脊椎动物宿主。疟原虫的感染阶段子孢子,在注入真皮后的数小时内会转移至肝脏。寄生虫生命周期的复杂性以及感染在肝脏中建立的速度阻碍了疫苗研发工作。为了增强对疟原虫的免疫力,我们制备了一种基于病毒样颗粒(VLP)的疫苗,该疫苗展示了TRIO的一个表位,TRIO是一种疟蚊唾液蛋白,已被证明可增强子孢子在真皮中的移动性和扩散。先前的研究表明,用TRIO进行被动免疫可预防肝脏感染,并与一种靶向疫苗协同作用。用TRIO VLP免疫小鼠会产生高滴度且持久的抗体反应,免疫后超过18个月抗体水平都没有显著下降。当与一种靶向环子孢子蛋白L9表位的抗疟疾疫苗联合使用时,TRIO VLP同样具有免疫原性。然而,在疟疾攻击小鼠模型中使用时,TRIO VLP仅提供了适度的感染保护,并没有增强L9 VLP所提供的保护。