Immunogenicity of mucosal COVID-19 vaccine candidates based on the highly attenuated vesicular stomatitis virus vector(VSV_(MT))in golden syrian hamster  

作　　者：Yong Ke En Zhang Jianming Guo Xiaoxiao Zhang Lei Wang Duo Chen Xinkui Fang Jianwei Zhu Feng Li Tao Sun Baohong Zhang 

机构地区：[1]Engineering Research Center of Cell&Therapeutic Antibody,Ministry of Education,School of Pharmacy,Shanghai Jiao Tong University,Shanghai 200240,China [2]School of Agriculture and Biology,Shanghai Jiao Tong University,Shanghai 200240,China [3]Shanghai Municipal Veterinary Key Laboratory,Shanghai 200240,China [4]Shanghai Public Health Clinical Center,Fudan Univeristy,Shanghai 201508,China

出　　处：《Acta Pharmaceutica Sinica B》2023年第12期4856-4874,共19页药学学报（英文版）

基　　金：supported by Biomedicine and Technology Supporting Project of Shanghai Science and Technology Innovation Plan(Grant Nos.22S11902200 and 20S11904900,China);Open grant of Engineering Research Center of Cell&Therapeutic Antibody,Ministry of Education,Shanghai Jiao Tong University(Grant No.19X110020009-003,China).

摘　　要：COVID-19 is caused by coronavirus SARS-CoV-2.Current systemic vaccines generally pro-vide limited protection against viral replication and shedding within the airway.Recombinant VSV(rVSV)is an effective vector which inducing potent and comprehensive immunities.Currently,there are two clinical trials investigating COVID-19vaccines based on VSV vectors.These vaccines were developed with spike protein of WA1 which administrated intramuscularly.Although intranasal route is ideal for activating mucosal immunity with VSV vector,safety is of concern.Thus,a highly attenuated rVSV with three amino acids mutations in matrix protein(VSV_(MT))was developed to construct safe mucosal vaccines against multiple SARS-CoV-2 variants of concern.It demonstrated that spike protein mutant lacking 21 amino acids in its cytoplasmic domain could rescue rVSV efficiently.VSV_(MT) indicated improved safeness compared with wild-type VSV as the vector encoding SARS-CoV-2 spike protein.With a single-dosed intranasal inoculation of rVSV_(ΔGMT)-S_(Δ21),potent SARS-CoV-2specific neutraliza-tion antibodies could be stimulated in animals,particularly in term of mucosal and cellular immunity.Strikingly,the chimeric VSV encoding S_(Δ21) of Delta-variant can induce more potent immune responses compared with those encoding S_(Δ21) of Omicron-or WA1-strain.VSV_(MT) is a promising platform to develop a mucosal vaccine for countering COVID-19.

关 键 词：COVID-19 Vesicular stomatitisvirus Matrix protein mutant Mucosal Vaccine Spike protein Variants of concerns Intranasal inoculation Cellular immunity 

分 类 号：R51[医药卫生—内科学]