Human enterovirus 71 viruses have been long circulating throughout the world. In this study, we performed a positive selection analysis of the VP1 genes of capsid proteins from Enterovirus 71 viruses. Our results show...Human enterovirus 71 viruses have been long circulating throughout the world. In this study, we performed a positive selection analysis of the VP1 genes of capsid proteins from Enterovirus 71 viruses. Our results showed that although most sites were under negative or neutral evolution, four positions of the VP1 genes were under positive selection pressure. This might account for the spread and frequent outbreaks of the viruses and the enhanced neurovirulence. In particular, position 98 might be involved in neutralizing antibodies, modulating the virus-receptor interaction and enhancing the virulence of the viruses. Moreover, both positions 145 and 241 might correlate to determine the receptor specificity. However, these positions did not display much difference in amino acid polymorphism. In addition, no position in the VP1 genes of viruses isolated from China was under positive selection.展开更多
Human Enterovirus 71(EV71)has emerged as one of the predominant causative agents of hand,foot and mouth disease(HFMD)with global impact.Despite the inactivated vaccine being licensed,other vaccine candidates based on ...Human Enterovirus 71(EV71)has emerged as one of the predominant causative agents of hand,foot and mouth disease(HFMD)with global impact.Despite the inactivated vaccine being licensed,other vaccine candidates based on advanced technology platforms are under development.In this report,we rationally designed and constructed two DNA-launched live attenuated vaccine candidates(pDL-EV71)under the control of specific promoters.In vitro and in vivo transfection with pDL-EV71 driven by the CMV promoter successfully yielded fully infectious EV71.More importantly,the administration of pDL-EV71 did not cause clinical symptoms following intracranial or intramuscular inoculation in neonatal and IFNα/βR/mice,demonstrating its safety profile.Moreover,a single-dose or two-dose immunization with pDL-EV71 elicited robust neutralizing antibodies against EV71 as well as an antigen-specific cellular response in mice.A single-dose immunization with 10μg of pDL-EV71 conferred complete protection against lethal EV71 infection in neonates born to immunized maternal mice.Overall,our present results demonstrate that pDL-EV71 is a safe and effective vaccine candidate against EV71 for further development.展开更多
Background Enterovirus 71 （EV71） and coxsackievirus A16 （Cox A16） are major causative agents for hand, foot and mouth disease （HFMD）. Studies indicate that the frequent HFMD outbreaks result in a few hundreds ch...Background Enterovirus 71 （EV71） and coxsackievirus A16 （Cox A16） are major causative agents for hand, foot and mouth disease （HFMD）. Studies indicate that the frequent HFMD outbreaks result in a few hundreds children＇s death in China in recent years. The vaccine and other research for HFMD need to be developed urgently. The aims of our study were： to explore dynamic development of mother-source neutralizing antibodies against EV71 and Cox A16 in infants from Jiangsu Province, China, and to provide the fundamental data for further establishing of corresponding immunization course. Methods Peripheral blood samples were collected from 133 of parturient women once immediately before delivery and their infants at two and seven months of age. Method of micro-dose cytopathogenic effect was used to measure neutralizing antibodies against EV71 and Cox A16, respectively. Results Seropositive rates of anti-EV71 and anti-Cox A16 in prenatal women were 79.7% （106/133） and 92.5% （123/133）, respectively; geometric mean titers （GMTs） were 29.0 and 61.9; 75.9% （101/133） prenatal women were both positive in anti-EV71 and anti-Cox A16; seropositive rates of anti-EV71 and anti-Cox A16 were 25.6% （34/133） and 38.3% （51/133） in infants at two months of age; GMTs were 12.3 and 18.0, respectively. GMTs of anti-EV71 were significantly higher for infants at seven months （82.6） compared with that at two months （P 〈0.05）, showing infants had inapparently infected by EV71 during two to seven months. Although only one offspring （0.75%） at seven months was found having anti-Cox A16 transfered from maternal, this observation suggested no maternal antibody may remain in infants at seven months. Conclusions The prevalence of EV71 and Cox A16 were relatively high in Jiangsu Province. Bivalent vaccine against both EV71 and Cox A16 should be developed, and the ideal time point for prime immunization for infants is around 2-5 months of age.展开更多
Hand, foot and mouth disease(HFMD) is a significant health concern in the Asia–Pacific regions for infants and young children in recent years. However, no vaccines or therapeutics are available at present. The causat...Hand, foot and mouth disease(HFMD) is a significant health concern in the Asia–Pacific regions for infants and young children in recent years. However, no vaccines or therapeutics are available at present. The causative agents for HFMD include human enterovirus 71(EV71), coxsackievirus A16(CVA16) and some other viruses. Recently, tremendous progress has been made in the development of monovalent and bivalent vaccines against HFMD. A few neutralizing monoclonal antibodies against EV71 or CVA16 have been identified and characterized. Here, we reviewed some achievements for the development of broadly protective vaccines and neutralizing antibodies against HFMD, and discussed challenges and prospects toward broadly protective multivalent vaccines and therapeutic antibodies against HFMD.展开更多
文摘Human enterovirus 71 viruses have been long circulating throughout the world. In this study, we performed a positive selection analysis of the VP1 genes of capsid proteins from Enterovirus 71 viruses. Our results showed that although most sites were under negative or neutral evolution, four positions of the VP1 genes were under positive selection pressure. This might account for the spread and frequent outbreaks of the viruses and the enhanced neurovirulence. In particular, position 98 might be involved in neutralizing antibodies, modulating the virus-receptor interaction and enhancing the virulence of the viruses. Moreover, both positions 145 and 241 might correlate to determine the receptor specificity. However, these positions did not display much difference in amino acid polymorphism. In addition, no position in the VP1 genes of viruses isolated from China was under positive selection.
基金supported by the National Key Research and Development Program of China(2021YFC2302503)the National Natural Science Foundation of China(82241069)+1 种基金Cheng-Feng Qin was supported by the National Science Fund for Distinguished Young Scholars(81925025)the Innovative Research Group from the NSFC(81621005).
文摘Human Enterovirus 71(EV71)has emerged as one of the predominant causative agents of hand,foot and mouth disease(HFMD)with global impact.Despite the inactivated vaccine being licensed,other vaccine candidates based on advanced technology platforms are under development.In this report,we rationally designed and constructed two DNA-launched live attenuated vaccine candidates(pDL-EV71)under the control of specific promoters.In vitro and in vivo transfection with pDL-EV71 driven by the CMV promoter successfully yielded fully infectious EV71.More importantly,the administration of pDL-EV71 did not cause clinical symptoms following intracranial or intramuscular inoculation in neonatal and IFNα/βR/mice,demonstrating its safety profile.Moreover,a single-dose or two-dose immunization with pDL-EV71 elicited robust neutralizing antibodies against EV71 as well as an antigen-specific cellular response in mice.A single-dose immunization with 10μg of pDL-EV71 conferred complete protection against lethal EV71 infection in neonates born to immunized maternal mice.Overall,our present results demonstrate that pDL-EV71 is a safe and effective vaccine candidate against EV71 for further development.
文摘Background Enterovirus 71 （EV71） and coxsackievirus A16 （Cox A16） are major causative agents for hand, foot and mouth disease （HFMD）. Studies indicate that the frequent HFMD outbreaks result in a few hundreds children＇s death in China in recent years. The vaccine and other research for HFMD need to be developed urgently. The aims of our study were： to explore dynamic development of mother-source neutralizing antibodies against EV71 and Cox A16 in infants from Jiangsu Province, China, and to provide the fundamental data for further establishing of corresponding immunization course. Methods Peripheral blood samples were collected from 133 of parturient women once immediately before delivery and their infants at two and seven months of age. Method of micro-dose cytopathogenic effect was used to measure neutralizing antibodies against EV71 and Cox A16, respectively. Results Seropositive rates of anti-EV71 and anti-Cox A16 in prenatal women were 79.7% （106/133） and 92.5% （123/133）, respectively; geometric mean titers （GMTs） were 29.0 and 61.9; 75.9% （101/133） prenatal women were both positive in anti-EV71 and anti-Cox A16; seropositive rates of anti-EV71 and anti-Cox A16 were 25.6% （34/133） and 38.3% （51/133） in infants at two months of age; GMTs were 12.3 and 18.0, respectively. GMTs of anti-EV71 were significantly higher for infants at seven months （82.6） compared with that at two months （P 〈0.05）, showing infants had inapparently infected by EV71 during two to seven months. Although only one offspring （0.75%） at seven months was found having anti-Cox A16 transfered from maternal, this observation suggested no maternal antibody may remain in infants at seven months. Conclusions The prevalence of EV71 and Cox A16 were relatively high in Jiangsu Province. Bivalent vaccine against both EV71 and Cox A16 should be developed, and the ideal time point for prime immunization for infants is around 2-5 months of age.
基金supported by the National Basic Research Program of China(2010CB912403)the National Natural Science Foundation of China(31370730 and 31070144)
文摘Hand, foot and mouth disease(HFMD) is a significant health concern in the Asia–Pacific regions for infants and young children in recent years. However, no vaccines or therapeutics are available at present. The causative agents for HFMD include human enterovirus 71(EV71), coxsackievirus A16(CVA16) and some other viruses. Recently, tremendous progress has been made in the development of monovalent and bivalent vaccines against HFMD. A few neutralizing monoclonal antibodies against EV71 or CVA16 have been identified and characterized. Here, we reviewed some achievements for the development of broadly protective vaccines and neutralizing antibodies against HFMD, and discussed challenges and prospects toward broadly protective multivalent vaccines and therapeutic antibodies against HFMD.
