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

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

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 (SΔ19 Rep) was generated. A single dose of SΔ19 Rep intranasal vaccination is sufficient to induce protective immunity against SARS-CoV-2 infection in hamsters. All the clones isolated from the SΔ19 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.

Original languageEnglish
Article number872047
JournalFrontiers in Immunology
Volume13
DOIs
StatePublished - 2 May 2022

Keywords

  • ACE2 transgenic mice
  • S1/S2 cleavage site
  • SARS-CoV-2 Spike
  • TMPRSS2
  • VSV
  • furin
  • pseudotype
  • replication-competent

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