Following the RTS,S malaria vaccine, which showed only partial protection with short-term memory, there is strong support to develop second-generation malaria vaccines that yield higher efficacy with longer duration. The use of replicating viral vectors to deliver subunit vaccines is of great interest due to their capacity to induce efficient cellular immune responses and long-term memory. The measles vaccine virus offers an efficient and safe live viral vector that could easily be implemented in the field. Here, we produced recombinant measles viruses (rMV) expressing malaria “gold standard” circumsporozoïte antigen (CS) of Plasmodium berghei (Pb) and Plasmodium falciparum (Pf) to test proof of concept of this delivery strategy. Immunization with rMV expressing PbCS or PfCS induced high antibody responses in mice that did not decrease for at least 22 weeks post-prime, as well as rapid development of cellular immune responses. The observed long-term memory response is key for development of second-generation malaria vaccines. Sterile protection was achieved in 33% of immunized mice, as usually observed with the CS antigen, and all other immunized animals were clinically protected from severe and lethal Pb ANKA-induced cerebral malaria. Further rMV-vectored malaria vaccine candidates expressing additional pre-erythrocytic and blood-stage antigens in combination with rMV expressing PfCS may provide a path to development of next generation malaria vaccines with higher efficacy.

继RTS，S疟疾疫苗仅表现出部分保护作用并具有短期记忆之后，大力支持开发第二代疟疾疫苗，该疫苗可产生更高的功效并持续更长的时间。由于其能够诱导有效的细胞免疫应答和长期记忆，使用复制型病毒载体递送亚单位疫苗引起了极大的兴趣。麻疹疫苗病毒提供了一种有效且安全的活病毒载体，可在野外轻松实施。在这里，我们生产了表达疟疾的重组麻疹病毒（rMV），其中包括伯氏疟原虫（Pb）和恶性疟原虫（Pf）的疟疾“金标准”环孢子抗原（CS））以测试此投放策略的概念证明。用表达rMV的Pb CS或Pf CS免疫可在小鼠中引发高抗体反应，这种反应在初次免疫后至少22周内未降低，并且细胞免疫反应迅速发展。观察到的长期记忆反应是开发第二代疟疾疫苗的关键。通常用CS抗原观察到，在33％的免疫小鼠中实现了无菌保护，并且在临床上保护了所有其他免疫动物免受Pb ANKA致死的致命致命性脑疟疾的侵害。此外RMV矢量化疟疾疫苗候选物表达的组合附加红细胞前和血液阶段抗原与RMV表达Pf的CS可能为开发更高功效的下一代疟疾疫苗提供一条途径。