Comparative Study Of The Protein Profilings In Thalamencephalon Of Rhesus Monkey Neonate Immunized And Uninmmunized With EV71 Inactived Vaccine And Followed By Viral Infection

Hand-foot-mouth disease (HFMD) is an acute infectious disease which caused by enterovirus. In recent years, the morbidity and mortality of HFMD are observably increased. There are more than 20 variety virus that cause HFMD and enterovirus 71 (EV71) is the major one. EV71 infection can cause diseases of the nervous system, such as meningitis, encephalitis, monoplegia, acute flaccid paralysis and so on. It also associated with non-nervous system such as HFMD, herpetic angina and pulmonary oedema. In severe patients, it can cause central nervous system complication and pulmonary oedema which are fatal diseases. At present, the research about EV71 mainly focuses on the etiology and epidemiology of the virus. The pathogenesis of the virus has not yet understood. Due to continuous expanding of HFMD caused by EV71 and absence of effective drugs, there is a compelling need to develop a safe and effective vaccine. An elementary inactivated vaccine which prepared from the diploid cell cultured virus is used in this study. In this research, the protective effects of this vaccine were tested in a classic animal model—rhesus monkey neonate.Animal immunized or non-immunized with inactived vaccine were inoculated with EV71 and examined. In vaccine immunized rhesus monkey neonate, viral RNA was detected from infected control each parts of animals the neural system tissue, but not form vaccinated one. The inactivated vaccine can induce the monkeys produce neutralizing antibody which could reach 1:512 in the serum at the 7th day after viral attack.It can form effective antivirus immune barrier. Immunohistochemistry researches show that the protection effects which inoculate with inactivated vaccine could induce virus multiplication.It can be sure that inoculate with this inactivated vaccine, there were no immunopathogenesis damage in animals.Further testing by pathological examination, comprehensive biopsy pathological observation and immunohistochemistry analysis were carried out and all results indicated that inactivated EV71 vaccine protected rhesus monkey from virus attack.Protein differential expression profiling of infected, vaccinated and control monkey brain tissue was analyzed by two-dimensional-electrophoresis and matrix assisted laser-desorption ionization time of flight mass spectrometry.48 proteins were found expressed differently in these group, including 8 cytoskeleton related proteins (6 microfilament related and 2 microtube related) which relate to maintain integrality of cytoskeleton structure and cell membrane,a heat shock protein which,4 proteins related to macromolecular biosynthesis (2 related with protein translation and 2 related with protein translocation and metabolism,13 metabolism related proteins (2 protein related with carbohydrate metabolism,6 protein related with lipids metabolism,5 protein related with amino acid metabolism),11 protein related with biological oxidation and 9 protein related with signal transduction. These results further confirmed the protective effects of inactivated vaccine and set the foundation for the research on the biological characters of host reaction during EV71 infection and mechanisms that vaccine protected the host from EV71 infection.