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Enhancement of safety and immunogenicity of the Chinese Hu191 measles virus vaccine by alteration of the S-adenosylmethionine (SAM) binding site in the large polymerase protein

The live-attenuated measles virus (MV) vaccine based on the Hu191 strain has played a significant role in controlling measles in China. However, it has considerable adverse effects that may cause public health burden. We hypothesize that the safety and efficacy of MV vaccine can be improved by alter...

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Autores principales: Wang, Yilong, Liu, Rongxian, Lu, Mijia, Yang, Yingzhi, Zhou, Duo, Hao, Xiaoqiang, Zhou, Dongming, Wang, Bin, Li, Jianrong, Huang, Yao-Wei, Zhao, Zhengyan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6413878/
https://www.ncbi.nlm.nih.gov/pubmed/29525671
http://dx.doi.org/10.1016/j.virol.2018.02.022
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author Wang, Yilong
Liu, Rongxian
Lu, Mijia
Yang, Yingzhi
Zhou, Duo
Hao, Xiaoqiang
Zhou, Dongming
Wang, Bin
Li, Jianrong
Huang, Yao-Wei
Zhao, Zhengyan
author_facet Wang, Yilong
Liu, Rongxian
Lu, Mijia
Yang, Yingzhi
Zhou, Duo
Hao, Xiaoqiang
Zhou, Dongming
Wang, Bin
Li, Jianrong
Huang, Yao-Wei
Zhao, Zhengyan
author_sort Wang, Yilong
collection PubMed
description The live-attenuated measles virus (MV) vaccine based on the Hu191 strain has played a significant role in controlling measles in China. However, it has considerable adverse effects that may cause public health burden. We hypothesize that the safety and efficacy of MV vaccine can be improved by altering the S-adenosylmethionine (SAM) binding site in the conserved region VI of the large polymerase protein. To test this hypothesis, we established an efficient reverse genetics system for the rMV-Hu191 strain and generated two recombinant MV-Hu191 carrying mutations in the SAM binding site. These two mutants grew to high titer in Vero cells, were genetically stable, and were significantly more attenuated in vitro and in vivo compared to the parental rMV-Hu191 vaccine strain. Importantly, both MV-Hu191 mutants triggered a higher neutralizing antibody than rMV-Hu191 vaccine and provided complete protection against MV challenge. These results demonstrate its potential for an improved MV vaccine candidate.
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spelling pubmed-64138782019-03-12 Enhancement of safety and immunogenicity of the Chinese Hu191 measles virus vaccine by alteration of the S-adenosylmethionine (SAM) binding site in the large polymerase protein Wang, Yilong Liu, Rongxian Lu, Mijia Yang, Yingzhi Zhou, Duo Hao, Xiaoqiang Zhou, Dongming Wang, Bin Li, Jianrong Huang, Yao-Wei Zhao, Zhengyan Virology Article The live-attenuated measles virus (MV) vaccine based on the Hu191 strain has played a significant role in controlling measles in China. However, it has considerable adverse effects that may cause public health burden. We hypothesize that the safety and efficacy of MV vaccine can be improved by altering the S-adenosylmethionine (SAM) binding site in the conserved region VI of the large polymerase protein. To test this hypothesis, we established an efficient reverse genetics system for the rMV-Hu191 strain and generated two recombinant MV-Hu191 carrying mutations in the SAM binding site. These two mutants grew to high titer in Vero cells, were genetically stable, and were significantly more attenuated in vitro and in vivo compared to the parental rMV-Hu191 vaccine strain. Importantly, both MV-Hu191 mutants triggered a higher neutralizing antibody than rMV-Hu191 vaccine and provided complete protection against MV challenge. These results demonstrate its potential for an improved MV vaccine candidate. Elsevier Inc. 2018-05 2018-03-15 /pmc/articles/PMC6413878/ /pubmed/29525671 http://dx.doi.org/10.1016/j.virol.2018.02.022 Text en © 2018 Elsevier Inc. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
spellingShingle Article
Wang, Yilong
Liu, Rongxian
Lu, Mijia
Yang, Yingzhi
Zhou, Duo
Hao, Xiaoqiang
Zhou, Dongming
Wang, Bin
Li, Jianrong
Huang, Yao-Wei
Zhao, Zhengyan
Enhancement of safety and immunogenicity of the Chinese Hu191 measles virus vaccine by alteration of the S-adenosylmethionine (SAM) binding site in the large polymerase protein
title Enhancement of safety and immunogenicity of the Chinese Hu191 measles virus vaccine by alteration of the S-adenosylmethionine (SAM) binding site in the large polymerase protein
title_full Enhancement of safety and immunogenicity of the Chinese Hu191 measles virus vaccine by alteration of the S-adenosylmethionine (SAM) binding site in the large polymerase protein
title_fullStr Enhancement of safety and immunogenicity of the Chinese Hu191 measles virus vaccine by alteration of the S-adenosylmethionine (SAM) binding site in the large polymerase protein
title_full_unstemmed Enhancement of safety and immunogenicity of the Chinese Hu191 measles virus vaccine by alteration of the S-adenosylmethionine (SAM) binding site in the large polymerase protein
title_short Enhancement of safety and immunogenicity of the Chinese Hu191 measles virus vaccine by alteration of the S-adenosylmethionine (SAM) binding site in the large polymerase protein
title_sort enhancement of safety and immunogenicity of the chinese hu191 measles virus vaccine by alteration of the s-adenosylmethionine (sam) binding site in the large polymerase protein
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6413878/
https://www.ncbi.nlm.nih.gov/pubmed/29525671
http://dx.doi.org/10.1016/j.virol.2018.02.022
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