Abstract：
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged as the prime challenge facing public health safety since 2019. Correspondingly, coronavirus disease 2019 (COVID-19) vaccines have been developed and administered worldwide, varying in design strategies, delivery routes, immunogenicity and protective efficacy. Here, a replication-competent vesicular stomatitis virus (VSV) vectored recombinant COVID-19 vaccine was constructed and evaluated in BALB/c mice and Syrian golden hamsters. In BALB/c mice, intramuscular (i.m.) inoculation of recombinant vaccine induced significantly higher humoral immune response than that of the intranasal (i.n.) inoculation group. Analyses of cellular immunity revealed that a Th1-biased cellular immune response was induced in i.n. inoculation group while both Th1 and Th2 T cells were activated in i.m. inoculation group. In golden hamsters, i.n. inoculation of the recombinant vaccine triggered robust humoral immune response and conferred prominent protective efficacy post-SARS-CoV-2 challenge, indicating a better protective immunity in the i.n. inoculation group than that of the i.m. inoculation group. This study provides an effective i.n.-delivered recombinant COVID-19 vaccine candidate and elucidates a route-dependent manner of this vaccine candidate in two most frequently applied small animal models. Moreover, the golden hamster is presented as an economical and convenient small animal model that precisely reflects the immune response and protective efficacy induced by replication-competent COVID-19 vaccine candidates in other SARS-CoV-2 susceptible animals and human beings, especially in the exploration of i.n. immunization.
摘要：
自2019年以来，严重急性呼吸道综合症冠状病毒2（SARS-CoV-2）已成为公共卫生安全面临的主要挑战。相应地,2019年冠状病毒病(COVID-19)疫苗已经在全球范围内开发和施用，不同的设计策略，交货路线,免疫原性和保护功效。这里,我们构建了一种复制型水疱性口炎病毒(VSV)载体重组COVID-19疫苗,并在BALB/c小鼠和叙利亚金仓鼠中进行了评估.在BALB/c小鼠中，重组疫苗的肌内（i.m.）接种诱导的体液免疫应答明显高于鼻内（i.n.）接种组。细胞免疫分析表明，在i.n.接种组中诱导了Th1偏向的细胞免疫应答，而在i.m.接种组中Th1和Th2T细胞均被激活。在金色仓鼠中，i.n.重组疫苗的接种引发了强大的体液免疫反应，并在SARS-CoV-2攻击后赋予了突出的保护功效，表明i.n.接种组比i.m.接种组具有更好的保护性免疫力。这项研究提供了一种有效的静脉注射重组COVID-19候选疫苗，并在两种最常用的小动物模型中阐明了该候选疫苗的途径依赖性方式。此外，金仓鼠是一种经济，方便的小动物模型，可准确反映具有复制能力的COVID-19疫苗候选物在其他SARS-CoV-2易感动物和人类中诱导的免疫反应和保护功效，特别是在i.n.免疫的探索中。
