Safety and immunogenicity of an experimental live combination vaccine against enterovirus 71 and coxsackievirus A16 in rhesus monkeys

Enterovirus 71 (EV-A71) and Coxsackievirus A16 (CV-A16) are the two most common pathogens causing hand, foot, and mouth disease (HFMD). Previously, we obtained one candidate live attenuated strain each for EV-A71 and CV-A16; here, we evaluated the safety and immunogenicity of a combinedlive vaccine...

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Main Authors: Ting Yang, Tianhong Xie, Xia Song, Dong Shen, Hua Li, Lei Yue, Qinfang Jiang, Fanli Zhu, Huaqing Meng, Runxiang Long, Rong Yang, Feiyu Luo, Zhongping Xie
Format: Article
Language:English
Published: Taylor & Francis Group 2020-07-01
Series:Human Vaccines & Immunotherapeutics
Subjects:
Online Access:http://dx.doi.org/10.1080/21645515.2019.1709353
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author Ting Yang
Tianhong Xie
Xia Song
Dong Shen
Hua Li
Lei Yue
Qinfang Jiang
Fanli Zhu
Huaqing Meng
Runxiang Long
Rong Yang
Feiyu Luo
Zhongping Xie
author_facet Ting Yang
Tianhong Xie
Xia Song
Dong Shen
Hua Li
Lei Yue
Qinfang Jiang
Fanli Zhu
Huaqing Meng
Runxiang Long
Rong Yang
Feiyu Luo
Zhongping Xie
author_sort Ting Yang
collection DOAJ
description Enterovirus 71 (EV-A71) and Coxsackievirus A16 (CV-A16) are the two most common pathogens causing hand, foot, and mouth disease (HFMD). Previously, we obtained one candidate live attenuated strain each for EV-A71 and CV-A16; here, we evaluated the safety and immunogenicity of a combinedlive vaccine against EV-A71 and CV-A16 generated from these two candidate strains. Rhesus monkeys were intramuscularly treated with a live combinationvaccine against both EV-A71 and CV-A16 or with either vaccine alone. No fever or atypical clinical signs were observed in any animals. Monkeys vaccinated with the combinationlive vaccine presented no notable pathological changes in the brain, spinal cord, lung, and liver; in contrast, these regions showed inflammatory cell infiltration in monkeys treated with EV-A71 alone or CV-A16 alone. Weak viremia was detected in plasma after inoculation with the combinationvaccine; however, the duration of viral shedding in feces was increased. Biochemical studies revealed a slight increase in aspartate aminotransferase levels in monkeys inoculated with the live combination vaccine; however, histopathological findings did not attribute this change to liver damage. We also found that the live combinationvaccine induced a dual humoral immune response. Cytokine analysis indicated that the combined EV-A71/CV-A16 vaccine significantly down-regulated interleukin-8 production. Here, we have demonstrated that the live attenuated EV-A71/CV-A16 vaccine was safe and could trigger a dual specific immune response. However, its immune protection efficacy requires further investigation.
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spelling doaj.art-9b4e5df6990f430fb0f8cdc0560647802023-09-22T08:45:35ZengTaylor & Francis GroupHuman Vaccines & Immunotherapeutics2164-55152164-554X2020-07-011671586159410.1080/21645515.2019.17093531709353Safety and immunogenicity of an experimental live combination vaccine against enterovirus 71 and coxsackievirus A16 in rhesus monkeysTing Yang0Tianhong Xie1Xia Song2Dong Shen3Hua Li4Lei Yue5Qinfang Jiang6Fanli Zhu7Huaqing Meng8Runxiang Long9Rong Yang10Feiyu Luo11Zhongping Xie12Chinese Academic Medical Sciences & Peking Union Medical CollegeChinese Academic Medical Sciences & Peking Union Medical CollegeChinese Academic Medical Sciences & Peking Union Medical CollegeChinese Academic Medical Sciences & Peking Union Medical CollegeChinese Academic Medical Sciences & Peking Union Medical CollegeChinese Academic Medical Sciences & Peking Union Medical CollegeChinese Academic Medical Sciences & Peking Union Medical CollegeChinese Academic Medical Sciences & Peking Union Medical CollegeThe Affiliated Hospital of GuiZhou Medical UniversityChinese Academic Medical Sciences & Peking Union Medical CollegeChinese Academic Medical Sciences & Peking Union Medical CollegeChinese Academic Medical Sciences & Peking Union Medical CollegeChinese Academic Medical Sciences & Peking Union Medical CollegeEnterovirus 71 (EV-A71) and Coxsackievirus A16 (CV-A16) are the two most common pathogens causing hand, foot, and mouth disease (HFMD). Previously, we obtained one candidate live attenuated strain each for EV-A71 and CV-A16; here, we evaluated the safety and immunogenicity of a combinedlive vaccine against EV-A71 and CV-A16 generated from these two candidate strains. Rhesus monkeys were intramuscularly treated with a live combinationvaccine against both EV-A71 and CV-A16 or with either vaccine alone. No fever or atypical clinical signs were observed in any animals. Monkeys vaccinated with the combinationlive vaccine presented no notable pathological changes in the brain, spinal cord, lung, and liver; in contrast, these regions showed inflammatory cell infiltration in monkeys treated with EV-A71 alone or CV-A16 alone. Weak viremia was detected in plasma after inoculation with the combinationvaccine; however, the duration of viral shedding in feces was increased. Biochemical studies revealed a slight increase in aspartate aminotransferase levels in monkeys inoculated with the live combination vaccine; however, histopathological findings did not attribute this change to liver damage. We also found that the live combinationvaccine induced a dual humoral immune response. Cytokine analysis indicated that the combined EV-A71/CV-A16 vaccine significantly down-regulated interleukin-8 production. Here, we have demonstrated that the live attenuated EV-A71/CV-A16 vaccine was safe and could trigger a dual specific immune response. However, its immune protection efficacy requires further investigation.http://dx.doi.org/10.1080/21645515.2019.1709353hand, foot and mouth disease (hfmd)enterovirus 71coxsackievirus 16combination immunization
spellingShingle Ting Yang
Tianhong Xie
Xia Song
Dong Shen
Hua Li
Lei Yue
Qinfang Jiang
Fanli Zhu
Huaqing Meng
Runxiang Long
Rong Yang
Feiyu Luo
Zhongping Xie
Safety and immunogenicity of an experimental live combination vaccine against enterovirus 71 and coxsackievirus A16 in rhesus monkeys
Human Vaccines & Immunotherapeutics
hand, foot and mouth disease (hfmd)
enterovirus 71
coxsackievirus 16
combination immunization
title Safety and immunogenicity of an experimental live combination vaccine against enterovirus 71 and coxsackievirus A16 in rhesus monkeys
title_full Safety and immunogenicity of an experimental live combination vaccine against enterovirus 71 and coxsackievirus A16 in rhesus monkeys
title_fullStr Safety and immunogenicity of an experimental live combination vaccine against enterovirus 71 and coxsackievirus A16 in rhesus monkeys
title_full_unstemmed Safety and immunogenicity of an experimental live combination vaccine against enterovirus 71 and coxsackievirus A16 in rhesus monkeys
title_short Safety and immunogenicity of an experimental live combination vaccine against enterovirus 71 and coxsackievirus A16 in rhesus monkeys
title_sort safety and immunogenicity of an experimental live combination vaccine against enterovirus 71 and coxsackievirus a16 in rhesus monkeys
topic hand, foot and mouth disease (hfmd)
enterovirus 71
coxsackievirus 16
combination immunization
url http://dx.doi.org/10.1080/21645515.2019.1709353
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