A Role for Immune Responses against Non-CS Components in the Cross-Species Protection Induced by Immunization with Irradiated Malaria Sporozoites
A Role for Immune Responses against Non-CS Components in the Cross-Species Protection Induced by Immunization with Irradiated Malaria Sporozoites
复制标题
针对非 CS 成分的免疫反应在辐照疟疾子孢子免疫诱导的跨物种保护中的作用
作者：
M. Mauduit;A. Grüner;R. Tewari;Nadya Depinay;M. Kayibanda;J. Chavatte;J. Franetich;A. Crisanti;D. Mazier;G. Snounou;L. Rénia
用经辐照的疟原虫子孢子免疫诱导啮齿动物、猴子和人类的无菌免疫。子孢子的主要表面成分环子孢子蛋白（CS）长期以来被认为是主要负责这种免疫的抗原，因此仍然是靶向寄生虫红细胞前期（PE）阶段的疫苗的主要候选抗原。然而，当我们最近发现用伯氏疟原虫品系的辐射子孢子（IrrSpz）免疫（其内源性CS被恶性疟原虫的CS取代）仍然赋予针对野生型伯氏疟原虫子孢子攻击的无菌保护时，CS的这种作用受到质疑。为了研究CS参与最近在两种啮齿动物寄生虫伯氏疟原虫和约氏疟原虫之间观察到的跨物种保护，我们采用我们的基因置换方法用于约氏疟原虫CS，并利用进行相互挑战的能力。总之，我们发现，免疫导致无菌免疫，无论CS的起源在免疫或挑战子孢子。然而，对于某些组合，对CS的免疫应答有助于获得保护性免疫，并且依赖于免疫IrrSpz剂量。尽管如此，当考虑来自所有跨种属免疫/攻毒的数据时，针对两种寄生虫种属共有的非CS寄生虫抗原的免疫应答在IrrSpz免疫诱导的无菌保护中发挥了重要作用。这开辟了开发单一疫苗制剂的前景，可以防止多种寄生虫物种。
Immunization with irradiated Plasmodium sporozoites induces sterile immunity in rodents, monkeys and humans. The major surface component of the sporozoite the circumsporozoite protein (CS) long considered as the antigen predominantly responsible for this immunity, thus remains the leading candidate antigen for vaccines targeting the parasite's pre-erythrocytic (PE) stages. However, this role for CS was questioned when we recently showed that immunization with irradiated sporozoites (IrrSpz) of a P. berghei line whose endogenous CS was replaced by that of P. falciparum still conferred sterile protection against challenge with wild type P. berghei sporozoites. In order to investigate the involvement of CS in the cross-species protection recently observed between the two rodent parasites P. berghei and P. yoelii, we adopted our gene replacement approach for the P. yoelii CS and exploited the ability to conduct reciprocal challenges. Overall, we found that immunization led to sterile immunity irrespective of the origin of the CS in the immunizing or challenge sporozoites. However, for some combinations, immune responses to CS contributed to the acquisition of protective immunity and were dependent on the immunizing IrrSpz dose. Nonetheless, when data from all the cross-species immunization/challenges were considered, the immune responses directed against non-CS parasite antigens shared by the two parasite species played a major role in the sterile protection induced by immunization with IrrSpz. This opens the perspective to develop a single vaccine formulation that could protect against multiple parasite species.