AUTHOR=Lin Jhe-Jhih , Tien Chih-Feng , Kuo Yi-Ping , Lin En-Ju , Tsai Wei-Hsiang , Chen Ming-Yu , Tsai Pei-Ju , Su Yu-Wen , Pathak Nikhil , Yang Jinn-Moon , Yu Chia-Yi , Chuang Zih-Shiuan , Wu Han-Chieh , Tsai Wan-Ting , Dai Shih-Syong , Liao Hung-Chun , Chai Kit Man , Su Yu-Siang , Chuang Tsung-Hsien , Liu Shih-Jen , Chen Hsin-Wei , Dou Horng-Yunn , Chen Feng-Jui , Chen Chiung-Tong , Liao Chin-Len , Yu Guann-Yi 

TITLE=Furin and TMPRSS2 Resistant Spike Induces Robust Humoral and Cellular Immunity Against SARS-CoV-2 Lethal Infection

JOURNAL=Frontiers in Immunology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.872047

DOI=10.3389/fimmu.2022.872047

ISSN=1664-3224

ABSTRACT=An effective COVID-19 vaccine against broad SARS-CoV-2 variants is still an unmet need. In the study, the vesicular stomatitis virus (VSV)-based vector was used to express the SARS-CoV-2 Spike protein to identify better vaccine designs. The replication-competent of the recombinant VSV-spike virus with C-terminal 19 amino acid truncation (S∆19 Rep) was generated. A single dose of S∆19 Rep intranasal vaccination is sufficient to induce protective immunity against SARS-CoV-2 infection in hamsters. All the clones isolated from the S∆19 Rep virus contained R682G mutation located at the Furin cleavage site. An additional S813Y mutation close to the TMPRSS2 cleavage site was identified in some clones. The enzymatic processing of S protein was blocked by these mutations. The vaccination of the R682G-S813Y virus produced a high antibody response against S protein and a robust S protein-specific CD8 T cell response. The vaccinated animals were protected from the lethal SARS-CoV-2 (delta variant) challenge. The S antigen with resistance to enzymatic processes by Furin and TMPRSS2 will provide better immunogenicity for vaccine design.