title: Similar protective immunity induced by an inactivated enterovirus 71 (EV71) vaccine in neonatal rhesus macaques and children.
abstract: During the development of enterovirus 71 (EV71) inactivated vaccine for preventing human hand, foot and mouth diseases (HFMD) by EV71 infection, an effective animal model is presumed to be significant and necessary. Our previous study demonstrated that the vesicles in oral regions and limbs potentially associated with viremia, which are the typical manifestations of HFMD, and remarkable pathologic changes were identified in various tissues of neonatal rhesus macaque during EV71 infection. Although an immune response in terms of neutralizing antibody and T cell memory was observed in animals infected by the virus or stimulated by viral antigen, whether such a response could be considered as an indicator to justify the immune response in individuals vaccinated or infected in a pandemic needs to be investigated. Here, a comparative analysis of the neutralizing antibody response and IFN-γ-specific T cell response in vaccinated neonatal rhesus macaques and a human clinical trial with an EV71 inactivated vaccine was performed, and the results showed the identical tendency and increased level of neutralizing antibody and the IFN-γ-specific T cell response stimulated by the EV71 antigen peptide. Importantly, the clinical protective efficacy against virus infection by the elicited immune response in the immunized population compared with the placebo control and the up-modulated gene profile associated with immune activation were similar to those in infected macaques. Further safety verification of this vaccine in neonatal rhesus macaques and children confirmed the potential use of the macaque as a reliable model for the evaluation of an EV71 candidate vaccine.
authors.affiliation: Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, Yunnan 650118, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, Yunnan 650118, China.
authors.forename: Lichun
authors.initials: L
authors.lastname: Wang
authors.affiliation: Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, Yunnan 650118, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Liao
authors.affiliation: Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, Yunnan 650118, China.
authors.forename: Longding
authors.initials: L
authors.lastname: Liu
authors.affiliation: Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, Yunnan 650118, China.
authors.forename: Kaili
authors.initials: K
authors.lastname: Ma
authors.affiliation: Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, Yunnan 650118, China; Jiangsu Convac Biotechnology Co., Ltd., Taizhou, Jiangsu 225300, China.
authors.forename: Erxia
authors.initials: E
authors.lastname: Yang
authors.affiliation: Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, Yunnan 650118, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, Yunnan 650118, China.
authors.forename: Yanchun
authors.initials: Y
authors.lastname: Che
authors.affiliation: Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, Yunnan 650118, China; Jiangsu Convac Biotechnology Co., Ltd., Taizhou, Jiangsu 225300, China.
authors.forename: Li
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, Yunnan 650118, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Pu
authors.affiliation: Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, Yunnan 650118, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Guo
authors.affiliation: Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, Yunnan 650118, China.
authors.forename: Min
authors.initials: M
authors.lastname: Feng
authors.affiliation: Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, Yunnan 650118, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liang
authors.affiliation: Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, Yunnan 650118, China; Jiangsu Convac Biotechnology Co., Ltd., Taizhou, Jiangsu 225300, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Cui
authors.affiliation: Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, Yunnan 650118, China.
authors.forename: Huai
authors.initials: H
authors.lastname: Yang
authors.affiliation: Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, Yunnan 650118, China. Electronic address: liqihan@imbcams.com.cn.
authors.forename: Qihan
authors.initials: Q
authors.lastname: Li
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D002675:Child, Preschool; D004195:Disease Models, Animal; D029821:Enterovirus A, Human / Q000276:immunology*; D005260:Female; D006232:Hand, Foot and Mouth Disease / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D006801:Humans; D007223:Infant; D007371:Interferon-gamma / Q000378:metabolism; D008253:Macaca mulatta; D008297:Male; D010919:Placebos / Q000008:administration & dosage; D013601:T-Lymphocytes / Q000276:immunology; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D010919:Placebos; D015164:Vaccines, Inactivated; D014765:Viral Vaccines; D007371:Interferon-gamma
keywords: Enterovirus 71 (EV71); Immune responses; Inactivated vaccine; Macaque