Department of Microbiology, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China.
State Key Laboratory for Emerging Infectious Diseases, the University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China.
Nat Commun. 2023 Apr 12;14(1):2081. doi: 10.1038/s41467-023-37697-1.
Current available vaccines for COVID-19 are effective in reducing severe diseases and deaths caused by SARS-CoV-2 infection but less optimal in preventing infection. Next-generation vaccines which are able to induce mucosal immunity in the upper respiratory to prevent or reduce infections caused by highly transmissible variants of SARS-CoV-2 are urgently needed. We have developed an intranasal vaccine candidate based on a live attenuated influenza virus (LAIV) with a deleted NS1 gene that encodes cell surface expression of the receptor-binding-domain (RBD) of the SARS-CoV-2 spike protein, designated DelNS1-RBD4N-DAF. Immune responses and protection against virus challenge following intranasal administration of DelNS1-RBD4N-DAF vaccines were analyzed in mice and compared with intramuscular injection of the BioNTech BNT162b2 mRNA vaccine in hamsters. DelNS1-RBD4N-DAF LAIVs induced high levels of neutralizing antibodies against various SARS-CoV-2 variants in mice and hamsters and stimulated robust T cell responses in mice. Notably, vaccination with DelNS1-RBD4N-DAF LAIVs, but not BNT162b2 mRNA, prevented replication of SARS-CoV-2 variants, including Delta and Omicron BA.2, in the respiratory tissues of animals. The DelNS1-RBD4N-DAF LAIV system warrants further evaluation in humans for the control of SARS-CoV-2 transmission and, more significantly, for creating dual function vaccines against both influenza and COVID-19 for use in annual vaccination strategies.
目前用于 COVID-19 的疫苗可有效降低由 SARS-CoV-2 感染引起的严重疾病和死亡，但在预防感染方面效果不太理想。急需开发下一代疫苗，这些疫苗能够在上呼吸道诱导黏膜免疫，以预防或减少由 SARS-CoV-2 的高传染性变体引起的感染。我们已经开发了一种基于缺失 NS1 基因的活减毒流感病毒（LAIV）的鼻内疫苗候选物，该基因编码 SARS-CoV-2 刺突蛋白的受体结合域（RBD）的细胞表面表达，命名为 DelNS1-RBD4N-DAF。在小鼠中分析了经鼻给予 DelNS1-RBD4N-DAF 疫苗后的免疫反应和对病毒攻击的保护作用，并与在仓鼠中肌内注射 BioNTech BNT162b2 mRNA 疫苗进行了比较。DelNS1-RBD4N-DAF LAIV 在小鼠和仓鼠中诱导了针对各种 SARS-CoV-2 变体的高水平中和抗体，并在小鼠中刺激了强大的 T 细胞反应。值得注意的是，用 DelNS1-RBD4N-DAF LAIV 而不是 BNT162b2 mRNA 接种可预防 SARS-CoV-2 变体（包括 Delta 和 Omicron BA.2）在动物呼吸道组织中的复制。DelNS1-RBD4N-DAF LAIV 系统值得在人类中进一步评估，以控制 SARS-CoV-2 的传播，更重要的是，开发针对流感和 COVID-19 的双重功能疫苗，用于年度接种策略。
