title: [Evaluation of immune responses and related patho-inflammatory reactions of a candidate inactivated EV71 vaccine in neonatal monkeys].
abstract: OBJECTIVE
  To evaluate the safety of enterovirus type 71 (EV71) inactivated vaccine (human diploid derived) for infection prevention in an animal model by investigating the immune responses and related patho-inflammatory reactions.
  
  
  METHODS
  In the neonatal monkey model for EV71 vaccine protection, vaccinated group (n = 4) and unvaccinated group (n = 4) were attacked with live virus at the same time, the parameters of clinical observations, antibodies and inflammatory factors in peripheral blood and cerebrospinal fluid (CSF) were detected. And the pathological changes in major organs were used to determine the patho-inflammatory reactions during the immune responses elicited by vaccination.
  
  
  RESULTS
  The neutralizing antibodies of vaccine group reach to 1:32. There was no obvious changes of inflammatory factors in peripheral blood and CSF of monkeys challenged or unchallenged by live virus. In peripheral blood of unvaccinated group, the level of basophilic granulocyte higher 4 - 5 times than normal level and the interferon-γ (IFN-γ) showed obvious increase. Live virus infected after 7 days, the interleukin-6 (IL-6) and IFN-γ in peripheral blood of unvaccinated group (18.5, 12.7 pg/ml) were higher than vaccinated group (10.2, 7.6 pg/ml). Furthermore, the IL-6 in CSF (102.0 pg/ml) had 4 - 5 times increased than vaccinated group (12.4 pg/ml) at 7 days after virus exposure. Meanwhile, the pathological analysis revealed that no obvious changes were detected in CNS and other organs of vaccinated monkeys challenged with live virus. However, the pathological damages induced by virus infection could be determined in the unvaccinated control monkeys, including neuronal damage, massive cellular infiltration associated with pulmonary edema/hemorrhage and pulmonary/bronchial damage due to an infiltration of inflammatory cells.
  
  
  CONCLUSIONS
  Capable of inducing an immune response, the EV71 inactivated vaccine offers protection to neonatal rhesus monkeys against the attacks of live virus. Based on the results of no patho-inflammatory reaction and pathological damage after viral infection in vaccinated animals, the excellent safety of this vaccine may be confirmed in neonatal monkey.
authors.affiliation: Chinese Academy of Medicine Sciences, Kunmimg, China.
authors.forename: Xue-mei
authors.initials: XM
authors.lastname: Zhang
authors.forename: Hong-ling
authors.initials: HL
authors.lastname: Zhao
authors.forename: Jing-jing
authors.initials: JJ
authors.lastname: Wang
authors.forename: Yun
authors.initials: Y
authors.lastname: Liao
authors.forename: Rui-xiong
authors.initials: RX
authors.lastname: Na
authors.forename: Li-chun
authors.initials: LC
authors.lastname: Wang
authors.forename: Long-ding
authors.initials: LD
authors.lastname: Liu
authors.forename: Jia-hong
authors.initials: JH
authors.lastname: Gao
authors.forename: Dong-hong
authors.initials: DH
authors.lastname: Tang
authors.forename: Cong-zhang
authors.initials: CZ
authors.lastname: Wang
authors.forename: Qi-han
authors.initials: QH
authors.lastname: Li
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D029821:Enterovirus A, Human / Q000276:immunology*; D004769:Enterovirus Infections / Q000276:immunology / Q000517:prevention & control*; D007109:Immunity; D007249:Inflammation / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism; D015850:Interleukin-6 / Q000134:cerebrospinal fluid; D008253:Macaca mulatta; D014611:Vaccination; D015164:Vaccines, Inactivated / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D015850:Interleukin-6; D015164:Vaccines, Inactivated; D014765:Viral Vaccines; D007371:Interferon-gamma