DataSheet_1_Safety and Immunogenicity Analysis of a Newcastle Disease Virus (NDV-HXP-S) Expressing the Spike Protein of SARS-CoV-2 in Sprague Dawley Rats.docx

Despite global vaccination efforts, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to evolve and spread globally. Relatively high vaccination rates have been achieved in most regions of the United States and several countries worldwide. However, access to vaccines in low- and mid-income countries (LMICs) is still suboptimal. Second generation vaccines that are universally affordable and induce systemic and mucosal immunity are needed. Here we performed an extended safety and immunogenicity analysis of a second-generation SARS-CoV-2 vaccine consisting of a live Newcastle disease virus vector expressing a pre-fusion stabilized version of the spike protein (NDV-HXP-S) administered intranasally (IN), intramuscularly (IM), or IN followed by IM in Sprague Dawley rats. Local reactogenicity, systemic toxicity, and post-mortem histopathology were assessed after the vaccine administration, with no indication of severe local or systemic reactions. Immunogenicity studies showed that the three vaccination regimens tested elicited high antibody titers against the wild type SARS-CoV-2 spike protein and the NDV vector. Moreover, high antibody titers were induced against the spike of B.1.1.7 (alpha), B.1.351 (beta) and B.1.617.2 (delta) variants of concern (VOCs). Importantly, robust levels of serum antibodies with neutralizing activity against the authentic SARS-CoV-2 USA‐WA1/2020 isolate were detected after the boost. Overall, our study expands the pre-clinical safety and immunogenicity characterization of NDV-HXP-S and reinforces previous findings in other animal models about its high immunogenicity. Clinical testing of this vaccination approach is ongoing in different countries including Thailand, Vietnam, Brazil and Mexico.

尽管全球疫苗接种工作持续推进，严重急性呼吸综合征冠状病毒2（SARS-CoV-2）仍在全球范围内不断变异并传播。美国多数地区及全球多个国家已实现较高的疫苗接种覆盖率，但中低收入国家（LMICs）的疫苗可及性仍有待提升。当前亟需一款全民可负担、同时诱导体液与黏膜免疫的第二代新冠疫苗。本研究针对以活新城疫病毒为载体、表达刺突蛋白预融合稳定型变体的NDV-HXP-S第二代SARS-CoV-2疫苗，在斯普拉格-道利（Sprague Dawley）大鼠中开展了扩展的安全性与免疫原性分析，测试的接种方案包括鼻内（intranasal, IN）接种、肌内（intramuscular, IM）接种，以及先鼻内再肌内的序贯接种。疫苗接种完成后，研究团队对受试动物的局部反应原性、全身毒性及死后组织病理学特征进行了评估，未观察到严重局部或全身不良反应的迹象。免疫原性研究结果显示，三种测试接种方案均可诱导针对野生型SARS-CoV-2刺突蛋白及新城疫病毒载体的高滴度抗体；此外，该疫苗还可诱导针对B.1.1.7（Alpha）、B.1.351（Beta）及B.1.617.2（Delta）等关注变异株（Variant of Concern, VOCs）刺突蛋白的高滴度抗体。尤为重要的是，加强免疫后可检测到针对真实SARS-CoV-2 USA-WA1/2020分离株的强效中和性血清抗体水平。总体而言，本研究扩展了NDV-HXP-S的临床前安全性与免疫原性表征工作，进一步验证了此前其他动物模型中关于该疫苗高免疫原性的研究结论。目前，该接种方案的临床试验正在泰国、越南、巴西及墨西哥等多个国家推进中。