RT Journal Article
SR Electronic
T1 A live attenuated influenza virus-vectored intranasal COVID-19 vaccine provides rapid, prolonged, and broad protection against SARS-CoV-2 infection
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.11.13.468472
DO 10.1101/2021.11.13.468472
A1 Junyu Chen
A1 Pui Wang
A1 Lunzhi Yuan
A1 Liang Zhang
A1 Limin Zhang
A1 Hui Zhao
A1 Congjie Chen
A1 Yaode Chen
A1 Jinle Han
A1 Jizong Jia
A1 Zhen Lu
A1 Junping Hong
A1 Liqiang Chen
A1 Changfa Fan
A1 Zicen Lu
A1 Qian Wang
A1 Rirong Chen
A1 Minping Cai
A1 Ruoyao Qi
A1 Xijing Wang
A1 Jian Ma
A1 Min Zhou
A1 Huan Yu
A1 Chunlan Zhuang
A1 Xiaohui Liu
A1 Qiangyuan Han
A1 Guosong Wang
A1 Yingying Su
A1 Quan Yuan
A1 Tong Cheng
A1 Ting Wu
A1 Xiangzhong Ye
A1 Changgui Li
A1 Tianying Zhang
A1 Jun Zhang
A1 Huachen Zhu
A1 Yixin Chen
A1 Honglin Chen
A1 Ningshao Xia
YR 2021
UL http://biorxiv.org/content/early/2021/11/15/2021.11.13.468472.abstract
AB Remarkable progress has been made in developing intramuscular vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); however, they are limited with respect to eliciting local immunity in the respiratory tract, which is the primary infection site for SARS-CoV-2. To overcome the limitations of intramuscular vaccines, we constructed a nasal vaccine candidate based on an influenza vector by inserting a gene encoding the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2, named CA4-dNS1-nCoV-RBD (dNS1-RBD). A preclinical study showed that in hamsters challenged 1 day and 7 days after single-dose vaccination or 6 months after booster vaccination, dNS1-RBD largely mitigated lung pathology, with no loss of body weight, caused by either the prototype-like strain or beta variant of SARS-CoV-2. Lasted data showed that the animals could be well protected against beta variant challenge 9 months after vaccination. Notably, the weight loss and lung pathological changes of hamsters could still be significantly reduced when the hamster was vaccinated 24 h after challenge. Moreover, such cellular immunity is relatively unimpaired for the most concerning SARS-CoV-2 variants. The protective immune mechanism of dNS1-RBD could be attributed to the innate immune response in the nasal epithelium, local RBD-specific T cell response in the lung, and RBD-specific IgA and IgG response. Thus, this study demonstrates that the intranasally delivered dNS1-RBD vaccine candidate may offer an important addition to fight against the ongoing COVID-19 pandemic, compensating limitations of current intramuscular vaccines, particularly at the start of an outbreak.Competing Interest StatementThe authors have declared no competing interest.