Frontiers in Immunology (May 2022)
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 Liu,
- Shih-Jen Liu,
- Shih-Jen Liu,
- Hsin-Wei Chen,
- Hsin-Wei Chen,
- Hsin-Wei Chen,
- Horng-Yunn Dou,
- Feng-Jui Chen,
- Chiung-Tong Chen,
- Chin-Len Liao,
- Guann-Yi Yu
Affiliations
- Jhe-Jhih Lin
- National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Taiwan
- Chih-Feng Tien
- National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Taiwan
- Yi-Ping Kuo
- National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Taiwan
- En-Ju Lin
- National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Taiwan
- Wei-Hsiang Tsai
- National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Taiwan
- Ming-Yu Chen
- Immunology Research Center, National Health Research Institutes, Zhunan, Taiwan
- Pei-Ju Tsai
- Immunology Research Center, National Health Research Institutes, Zhunan, Taiwan
- Yu-Wen Su
- Immunology Research Center, National Health Research Institutes, Zhunan, Taiwan
- Nikhil Pathak
- Department of Biological Science and Technology, National Yang Ming Chiao Tung University, Hsinchu, Taiwan
- Jinn-Moon Yang
- Department of Biological Science and Technology, National Yang Ming Chiao Tung University, Hsinchu, Taiwan
- Chia-Yi Yu
- National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Taiwan
- Zih-Shiuan Chuang
- National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Taiwan
- Han-Chieh Wu
- National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Taiwan
- Wan-Ting Tsai
- National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Taiwan
- Shih-Syong Dai
- National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Taiwan
- Hung-Chun Liao
- National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Taiwan
- Kit Man Chai
- National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Taiwan
- Yu-Siang Su
- National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Taiwan
- Tsung-Hsien Chuang
- Immunology Research Center, National Health Research Institutes, Zhunan, Taiwan
- Shih-Jen Liu
- National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Taiwan
- Shih-Jen Liu
- Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan
- Shih-Jen Liu
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Hsin-Wei Chen
- National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Taiwan
- Hsin-Wei Chen
- Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan
- Hsin-Wei Chen
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Horng-Yunn Dou
- National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Taiwan
- Feng-Jui Chen
- National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Taiwan
- Chiung-Tong Chen
- Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Zhunan, Taiwan
- Chin-Len Liao
- National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Taiwan
- Guann-Yi Yu
- National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Taiwan
- DOI
- https://doi.org/10.3389/fimmu.2022.872047
- Journal volume & issue
-
Vol. 13
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.
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