title: A safety study of inactivated Enterovirus 71 vaccine.
abstract: Enterovirus 71 (EV71) is one of the major causative agents for hand, foot and mouth disease (HFMD) in childhood. Nowadays, HFMD or EV71 infections have already become an important public health issue throughout the world. Vaccination may be the most effective measure to control the transmission of the virus. Therefore, to pave EV71 vaccine into human clinical trial, in the present study a comprehensive preclinical safety assessment of inactivated EV71 vaccine including single- and repeat-dose toxicity studies were conducted in rats and cynomolgus monkeys. No abnormal findings were observed in rats following single intramuscular administration with EV71 vaccine (640 U). The results also showed no obvious systemic toxicities from four repetitive intramuscular injections, with a 14-d interval, of two dosages of EV71 vaccine in the two animal species. Antinuclear antibody response was not detected after the repeated administrations. Histopathological examination demonstrated the minimal to severe inflammatory changes in muscle tissues of the injection sites in EV71 vaccine-injected animals and most of findings have been improved over time. Furthermore, test article could induce highly EV71-specfic neutralizing antibody response in both animal species. Taken together, these data suggested a favorable safety profile for inactivated EV71 vaccine and supported this product to enter human phase I clinical trial.
authors.affiliation: Graduate School of Peking Union Medical College; Dongcheng District, Beijing, P.R. China; National Center for Safety Evaluation of Drugs; National Institutes for Food and Drug Control; Beijing, P.R. China.
authors.forename: Xiao-bing
authors.initials: XB
authors.lastname: Zhou
authors.forename: Jian-jun
authors.initials: JJ
authors.lastname: Lu
authors.forename: Yun-shui
authors.initials: YS
authors.lastname: Jiang
authors.forename: Yan
authors.initials: Y
authors.lastname: Huo
authors.forename: Ju-feng
authors.initials: JF
authors.lastname: Wang
authors.forename: Kang-feng
authors.initials: KF
authors.lastname: Zhou
authors.forename: Bo
authors.initials: B
authors.lastname: Li
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D029821:Enterovirus A, Human / Q000276:immunology*; D005260:Female; D006232:Hand, Foot and Mouth Disease / Q000276:immunology* / Q000517:prevention & control*; D008252:Macaca fascicularis; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D015164:Vaccines, Inactivated / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use; D014765:Viral Vaccines / Q000009:adverse effects* / Q000276:immunology / Q000627:therapeutic use*
chemical_list: D000974:Antibodies, Antinuclear; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D015164:Vaccines, Inactivated; D014765:Viral Vaccines
keywords: Enterovirus 71; and mouth disease; cynomolgus monkey; foot; hand; inactivated vaccine; rat; safety assessment