Green Tea Catechin-Inactivated Viral Vaccine Platform

Traditionally, chemical agents such as formalin (FA) and β-propiolactone (BPL) have long been used for the preparation of inactivated vaccines or toxoids. It has been shown that FA extensively modifies vaccine antigens and thus affects immunogenicity profiles, sometimes compromising the protective e...

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Main Authors: Yun H. Lee, Yo H. Jang, Young H. Byun, Yucheol Cheong, Paul Kim, Young J. Lee, Yoon J. Lee, Je M. Sung, Ahyun Son, Hye M. Lee, Jinhee Lee, Seung W. Yang, Jae-Min Song, Baik L. Seong
Format: Article
Language:English
Published: Frontiers Media S.A. 2017-12-01
Series:Frontiers in Microbiology
Subjects:
Online Access:http://journal.frontiersin.org/article/10.3389/fmicb.2017.02469/full
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author Yun H. Lee
Yo H. Jang
Young H. Byun
Yucheol Cheong
Paul Kim
Young J. Lee
Yoon J. Lee
Je M. Sung
Ahyun Son
Hye M. Lee
Jinhee Lee
Seung W. Yang
Jae-Min Song
Baik L. Seong
Baik L. Seong
author_facet Yun H. Lee
Yo H. Jang
Young H. Byun
Yucheol Cheong
Paul Kim
Young J. Lee
Yoon J. Lee
Je M. Sung
Ahyun Son
Hye M. Lee
Jinhee Lee
Seung W. Yang
Jae-Min Song
Baik L. Seong
Baik L. Seong
author_sort Yun H. Lee
collection DOAJ
description Traditionally, chemical agents such as formalin (FA) and β-propiolactone (BPL) have long been used for the preparation of inactivated vaccines or toxoids. It has been shown that FA extensively modifies vaccine antigens and thus affects immunogenicity profiles, sometimes compromising the protective efficacy of the vaccines or even exacerbating the disease upon infection. In this study, we show that natural catechins from green tea extracts (GT) can be used as an inactivating agent to prepare inactivated viral vaccines. GT treatment resulted in complete and irreversible inactivation of influenza virus as well as dengue virus. In contrast to FA that reacted extensively with multiple amino acids including lysine, a major anchor residue for epitope binding to MHC molecules, GT catechin epigallocatechin-3-gallate (EGCG) crosslinked primarily with cysteine residues and thus preserved the major epitopes of the influenza hemagglutinin. In a mouse model, vaccination with GT-inactivated influenza virus (GTi virus) elicited higher levels of viral neutralizing antibodies than FA-inactivated virus (FAi virus). The vaccination completely protected the mice from a lethal challenge and restricted the challenge viral replication in the lungs. Of note, the quality of antibody responses of GTi virus was superior to that with FAi virus, in terms of the magnitude of antibody titer, cross-reactivity to hetero-subtypes of influenza viruses, and the avidity to viral antigens. As the first report of using non-toxic natural compounds for the preparation of inactivated viral vaccines, the present results could be translated into a clinically relevant vaccine platform with improved efficacy, safety, productivity, and public acceptance.
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spelling doaj.art-3d20ee1c27024dcdb108dfab920e08422022-12-22T01:12:18ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2017-12-01810.3389/fmicb.2017.02469303330Green Tea Catechin-Inactivated Viral Vaccine PlatformYun H. Lee0Yo H. Jang1Young H. Byun2Yucheol Cheong3Paul Kim4Young J. Lee5Yoon J. Lee6Je M. Sung7Ahyun Son8Hye M. Lee9Jinhee Lee10Seung W. Yang11Jae-Min Song12Baik L. Seong13Baik L. Seong14Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, South KoreaDepartment of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, South KoreaDepartment of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, South KoreaDepartment of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, South KoreaDepartment of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, South KoreaDepartment of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, South KoreaDepartment of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, South KoreaDepartment of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, South KoreaDepartment of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, South KoreaDepartment of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, South KoreaDepartment of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, South KoreaDepartment of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, South KoreaDepartment of Global Medical Science, Health and Wellness College, Sungshin Women’s University, Seoul, South KoreaDepartment of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, South KoreaVaccine Translational Research Center, Yonsei University, Seoul, South KoreaTraditionally, chemical agents such as formalin (FA) and β-propiolactone (BPL) have long been used for the preparation of inactivated vaccines or toxoids. It has been shown that FA extensively modifies vaccine antigens and thus affects immunogenicity profiles, sometimes compromising the protective efficacy of the vaccines or even exacerbating the disease upon infection. In this study, we show that natural catechins from green tea extracts (GT) can be used as an inactivating agent to prepare inactivated viral vaccines. GT treatment resulted in complete and irreversible inactivation of influenza virus as well as dengue virus. In contrast to FA that reacted extensively with multiple amino acids including lysine, a major anchor residue for epitope binding to MHC molecules, GT catechin epigallocatechin-3-gallate (EGCG) crosslinked primarily with cysteine residues and thus preserved the major epitopes of the influenza hemagglutinin. In a mouse model, vaccination with GT-inactivated influenza virus (GTi virus) elicited higher levels of viral neutralizing antibodies than FA-inactivated virus (FAi virus). The vaccination completely protected the mice from a lethal challenge and restricted the challenge viral replication in the lungs. Of note, the quality of antibody responses of GTi virus was superior to that with FAi virus, in terms of the magnitude of antibody titer, cross-reactivity to hetero-subtypes of influenza viruses, and the avidity to viral antigens. As the first report of using non-toxic natural compounds for the preparation of inactivated viral vaccines, the present results could be translated into a clinically relevant vaccine platform with improved efficacy, safety, productivity, and public acceptance.http://journal.frontiersin.org/article/10.3389/fmicb.2017.02469/fullinfluenza virusgreen teacatechinsinactivated vaccineformalin
spellingShingle Yun H. Lee
Yo H. Jang
Young H. Byun
Yucheol Cheong
Paul Kim
Young J. Lee
Yoon J. Lee
Je M. Sung
Ahyun Son
Hye M. Lee
Jinhee Lee
Seung W. Yang
Jae-Min Song
Baik L. Seong
Baik L. Seong
Green Tea Catechin-Inactivated Viral Vaccine Platform
Frontiers in Microbiology
influenza virus
green tea
catechins
inactivated vaccine
formalin
title Green Tea Catechin-Inactivated Viral Vaccine Platform
title_full Green Tea Catechin-Inactivated Viral Vaccine Platform
title_fullStr Green Tea Catechin-Inactivated Viral Vaccine Platform
title_full_unstemmed Green Tea Catechin-Inactivated Viral Vaccine Platform
title_short Green Tea Catechin-Inactivated Viral Vaccine Platform
title_sort green tea catechin inactivated viral vaccine platform
topic influenza virus
green tea
catechins
inactivated vaccine
formalin
url http://journal.frontiersin.org/article/10.3389/fmicb.2017.02469/full
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