A single intranasal dose of human parainfluenza virus type 3-vectored vaccine induces effective antibody and tissue-resident T cell response in the lungs and protects hamsters against SARS-CoV-2

Respiratory tract vaccination has an advantage of needle-free delivery and induction of mucosal immune response in the portal of SARS-CoV-2 entry. We utilized human parainfluenza virus type 3 vector to generate constructs expressing the full spike (S) protein of SARS-CoV-2, its S1 subunit, or the receptor-binding domain, and tested them in hamsters as single-dose intranasal vaccines. The construct bearing full-length S induced high titers of neutralizing antibodies specific to S protein domains critical to the protein functions. Robust tissue-resident T cell responses in the lungs were also induced, which represent an additional barrier to infection and should be less sensitive than the antibody responses to mutations present in SARS-CoV-2 variants. Following SARS-CoV-2 challenge, animals were protected from the disease and detectable viral replication. Vaccination prevented induction of gene pathways associated with inflammation. These results indicate advantages of respiratory vaccination against COVID-19 and inform the design of mucosal SARS-CoV-2 vaccines. Overall design: 5 replicates each of vaccinated and unvaccinated hamsters were infected with SARS-CoV-2, followed by RNA extraction from lung tissue 3 days post-infection. 4 unvaccinated and uninfected hamsters were used as naïve controls.

呼吸道疫苗接种具有无需针头递送的显著优势，且可在严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的入侵门户诱导黏膜免疫应答。本研究以人3型副流感病毒为载体，构建了可表达SARS-CoV-2全长刺突（S）蛋白、其S1亚基或受体结合域的重组载体，并以仓鼠为模型，测试其作为单剂鼻内疫苗的效果。携带全长S蛋白的重组载体可诱导针对S蛋白功能关键结构域的高滴度中和抗体，同时还可在肺部诱导强效的组织驻留T细胞应答——这类应答可作为感染的额外防御屏障，且相较于针对SARS-CoV-2变异株突变的抗体应答，其对突变的敏感性更低。经SARS-CoV-2攻毒后，受试仓鼠可免受疾病侵害且未检测到病毒复制；疫苗接种还可抑制炎症相关基因通路的激活。上述结果证实了呼吸道疫苗接种对抗COVID-19的优势，可为黏膜途径SARS-CoV-2疫苗的研发提供理论参考。本研究的实验设计如下：将接种组与未接种组仓鼠各设置5个生物学重复，以SARS-CoV-2进行攻毒，于感染后3天提取肺组织总RNA。另选取4只未接种且未感染的仓鼠作为未致敏对照（naïve controls）。