The MOPEVAC multivalent vaccine induces sterile protection against New World Arenaviruses in non-human primates

Pathogenic New World arenaviruses (NWAs) cause hemorrhagic fevers and can have high mortality rates, as shown in recent outbreaks in South America. Neutralizing antibodies (Nabs) are critical for protection from NWAs. Having shown that the MOPEVAC vaccine, based on a hyper-attenuated arenavirus, induces NAbs against Lassa fever, we hypothesized that expression of NWA glycoproteins in this platform might protect against NWAs. Cynomolgus monkeys immunized with MOPEVACMAC, targeting Machupo virus, prevented the lethality of this virus and induced partially NWA-cross-reactive Nabs. We then developed the pentavalent MOPEVACNEW vaccine, expressing glycoproteins from all pathogenic South American NWAs. Immunization of cynomolgus monkeys with MOPEVACNEW induced Nabs against five NWAs, strong innate followed by adaptive immune responses as detected by transcriptomics, and provided sterile protection against Machupo virus and the genetically distant Guanarito virus. MOPEVACNEW may thus be efficient to protect against existing and, potentially, emerging NWAs.致病性新世界沙粒病毒（New World arenaviruses, NWAs）可引发出血热，且致死率居高不下，这在近期南美洲暴发的相关疫情中已得到验证。中和抗体（Neutralizing antibodies, Nabs）是抵御NWAs感染的关键免疫效应分子。本团队前期研究证实，基于高度减毒沙粒病毒载体构建的MOPEVAC疫苗可诱导针对拉沙热的中和抗体，据此我们提出假说：在该载体平台中表达NWAs糖蛋白，或可实现对NWAs感染的有效防护。针对马秋波病毒的MOPEVACMAC疫苗免疫食蟹猴后，可抵御该病毒的致死性攻击，并诱导出部分NWAs交叉反应性中和抗体。在此基础上，本团队开发了五价MOPEVACNEW疫苗，该疫苗可表达所有致病性南美洲NWAs的糖蛋白。对食蟹猴进行MOPEVACNEW免疫后，可诱导针对5种NWAs的中和抗体，通过转录组学检测可观察到强烈的天然免疫应答与后续的适应性免疫应答，且可实现对马秋波病毒及遗传距离较远的瓜纳里托病毒的无菌性保护。综上，MOPEVACNEW有望高效防护现有乃至潜在新发的NWAs感染。