title: A neonatal mouse model for the evaluation of antibodies and vaccines against coxsackievirus A6.
abstract: Coxsackievirus A6 (CA6) can induce atypical hand, foot, and mouth disease, which is characterized by severe rash, onychomadesis and a higher rate of infection in adults. Increasing epidemiological data indicated that outbreaks of CA6-associated hand, foot, and mouth disease have markedly increased worldwide in recent years. However, the current body of knowledge on the infection, pathogenic mechanism, and immunogenicity of CA6 is still very limited. In this study, we established the first neonatal mouse model for the evaluation of antibodies and vaccines against CA6. The CA6 strain CA6/141 could infect a one-day-old BALB/c mouse through intraperitoneal and intracerebral routes. The infected mice developed clinical symptoms, such as inactivity, wasting, hind-limb paralysis and even death. Pathological examination indicated that CA6 showed special tropism to skeletal muscles and skin, but not to nervous system or cardiac muscles. Infections with CA6 could induce vesicles in the dermis without a rash in mice, and the CA6 antigen was mainly localized in hair follicles. The strong tropism of CA6 to the skin may be related to its severe clinical features in infants. This mouse model was further applied to evaluate the efficacy of a therapeutic antibody and an experimental vaccine against CA6. A potential mAb 1D5 could fully protect mice from a lethal CA6 infection and also showed good therapeutic effects in the CA6-infected mice. In addition, an inactivated CA6 vaccine was evaluated through maternal immunization and showed 100% protection of neonatal mice from lethal CA6 challenge. Collectively, these results indicate that this infection model will be a useful tool in future studies on vaccines and antiviral reagents against CA6.
authors: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, Xiamen University, Xiamen, China.
authors: Lisheng
authors: L
authors: Yang
authors: National Institutes for Food and Drug Control, Beijing, China.
authors: Qunying
authors: Q
authors: Mao
authors: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, Xiamen University, Xiamen, China.
authors: Shuxuan
authors: S
authors: Li
authors: National Institutes for Food and Drug Control, Beijing, China.
authors: Fan
authors: F
authors: Gao
authors: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, Xiamen University, Xiamen, China.
authors: Huan
authors: H
authors: Zhao
authors: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, Xiamen University, Xiamen, China.
authors: Yajing
authors: Y
authors: Liu
authors: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, Xiamen University, Xiamen, China.
authors: Junkai
authors: J
authors: Wan
authors: Beijing Wantai Biological Pharmacy Enterprise, Beijing, China.
authors: Xiangzhong
authors: X
authors: Ye
authors: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, Xiamen University, Xiamen, China.
authors: Ningshao
authors: N
authors: Xia
authors: State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, Xiamen University, Xiamen, China. Electronic address: tcheng@xmu.edu.cn.
authors: Tong
authors: T
authors: Cheng
authors: National Institutes for Food and Drug Control, Beijing, China. Electronic address: lzhenglun@126.com.
authors: Zhenglun
authors: Z
authors: Liang
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000906:Antibodies / Q000008:administration & dosage / Q000627:therapeutic use*; D003384:Coxsackievirus Infections / Q000276:immunology* / Q000517:prevention & control / Q000628:therapy / Q000821:virology; D004195:Disease Models, Animal; D004770:Enterovirus / Q000276:immunology; D005260:Female; D006232:Hand, Foot and Mouth Disease / Q000276:immunology / Q000517:prevention & control; D051379:Mice; D008807:Mice, Inbred BALB C; D012867:Skin / Q000821:virology; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000276:immunology*; D056189:Viral Tropism
chemical_list: D000906:Antibodies; D015164:Vaccines, Inactivated
keywords: Animal model; Antibody; Coxsackievirus A6; Vaccine