Ouyang Maggie Jing, Ao Zhujun, Olukitibi Titus A, Lawrynuik Peter, Shieh Christopher, Kung Sam K P, Fowke Keith R, Kobasa Darwyn, Yao Xiaojian
Laboratory of Molecular Human Retrovirology, Department of Medical Microbiology and Infectious Diseases, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, 508-745 Bannatyne Ave, Winnipeg, MB R3E 0J9, Canada.
Department of Medical Microbiology and Infectious Diseases, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, 745 Bannatyne Ave, Winnipeg, MB R3E 0J9, Canada.
Vaccines (Basel). 2023 Aug 23;11(9):1404. doi: 10.3390/vaccines11091404.
COVID-19 and influenza both cause enormous disease burdens, and vaccines are the primary measures for their control. Since these viral diseases are transmitted through the mucosal surface of the respiratory tract, developing an effective and convenient mucosal vaccine should be a high priority. We previously reported a recombinant vesicular stomatitis virus (rVSV)-based bivalent vaccine (v-EM2/SPΔC1) that protects animals from both SARS-CoV-2 and influenza viruses via intramuscular and intranasal immunization. Here, we further investigated the immune response induced by oral immunization with this vaccine and its protective efficacy in mice. The results demonstrated that the oral delivery, like the intranasal route, elicited strong and protective systemic immune responses against SARS-CoV-2 and influenza A virus. This included high levels of neutralizing antibodies (NAbs) against SARS-CoV-2, as well as strong anti-SARS-CoV-2 spike protein (SP) antibody-dependent cellular cytotoxicity (ADCC) and anti-influenza M2 ADCC responses in mice sera. Furthermore, it provided efficient protection against challenge with influenza H1N1 virus in a mouse model, with a 100% survival rate and a significantly low lung viral load of influenza virus. All these findings provide substantial evidence for the effectiveness of oral immunization with the rVSV bivalent vaccine.
新型冠状病毒肺炎（COVID-19）和流感都造成了巨大的疾病负担，而疫苗是控制这些疾病的主要措施。由于这些病毒性疾病通过呼吸道黏膜表面传播，开发一种有效且便捷的黏膜疫苗应成为首要任务。我们之前报道了一种基于重组水疱性口炎病毒（rVSV）的二价疫苗（v-EM2/SPΔC1），该疫苗通过肌肉注射和鼻内免疫可保护动物免受严重急性呼吸综合征冠状病毒2（SARS-CoV-2）和流感病毒的侵害。在此，我们进一步研究了该疫苗口服免疫诱导的免疫反应及其在小鼠中的保护效果。结果表明，与鼻内途径一样，口服给药可引发针对SARS-CoV-2和甲型流感病毒的强烈且具有保护性的全身免疫反应。这包括小鼠血清中针对SARS-CoV-2的高水平中和抗体（NAbs），以及强烈的抗SARS-CoV-2刺突蛋白（SP）抗体依赖性细胞毒性（ADCC）和抗流感M2 ADCC反应。此外，在小鼠模型中，它对甲型H1N1流感病毒攻击提供了有效的保护，存活率达100%，且肺部流感病毒载量显著降低。所有这些发现为rVSV二价疫苗口服免疫的有效性提供了充分证据。
