Background Circulating enterovirus 71 (EV-A71)-associated hand foot and mouth disease is

Background Circulating enterovirus 71 (EV-A71)-associated hand foot and mouth disease is on the rise in the Asian-Pacific region. viruses to neonatal mice that were born to immunized female mice. The sera of the immunized dams and their pups showed higher neutralization titers against multiple circulating EV-A71 viruses. Conclusions Thus our newly established animal model using primary EV-A71 isolates is helpful for future studies on viral pathogenesis and vaccine and drug development. species A genogroup in the family. It began circulating in the Netherlands as early as 1963 and was first described in the USA in 1969 [1 2 EV-A71 and Coxsackievirus A16 (CV-A16) are the two major etiological agents that cause hand foot and mouth disease (HFMD); Rabbit Polyclonal to BCAS2. periodic large epidemics have occurred in recent decades and it has become a severe public health problem [3-9]. Previous studies have shown that EV-A71 usually causes HFMD with severe neurological complications including aseptic meningitis brainstem encephalitis poliomyelitis encephalomyelitis and even death [10-20]. In 1997 a large outbreak of HFMD caused by highly neurovirulent EV-A71 emerged in Malaysia and led to 41 deaths among young children [21]. In 1998 a large outbreak of enterovirus infection occurred in Taiwan that resulted in 405 severe cases in children and 78 deaths. Of the 78 children who died 71 (91?%) were under 5?years of age [22]. In 2011 the largest recorded outbreak of EV-A71-associated HFMD occurred in mainland China comprising >1.7 million Abametapir cases and including 27 0 patients who exhibited severe neurological complications and 905 deaths [23]. EV-A71 has one serotype and can be classified into three genotypes (A B and C) and many subtypes (A B0 B1-B5 and C1-C5). In Taiwan the major subtypes of EV-A71 were C2 in 1998 B4 in the 2002 epidemic C4 in the 2004-2005 epidemic C5 in the 2006-2007 epidemic B5 in the 2008-2009 epidemic C4 in the 2010 epidemic and B5 in the 2011-2012 epidemic [24 25 The predominant EV-A71 genotypes detected in Singapore were B3 in 1997-1999 B4 in 2000-2003 C1 in 2002 and B5 in 2006-2008. In mainland China in 1998-2011 all the strains were clustered in the C4 subgenotype of EV-A71. Most research has been focused on developing vaccines against EV-A71 [26-35]. Given the successful experience in the development of inactivated whole viruses for poliovirus influenza virus and rabies virus inactivated EV-A71 Abametapir whole-virus vaccines have been produced by five manufacturers in mainland China Taiwan and Singapore. These vaccines have completed Phase III (mainland China) and Phase I (Taiwan and Singapore) respectively [32]. In mainland China Beijing Vigoo Biological Co. Ltd (Vigoo) Sinovac Biotec Co. Ltd (Sinovac) and the Chinese Academy of Medical Technology (CAMS) have used EV-A71 subgenotype C4 like a disease seed because it is the common genotype in mainland China; however Vigoo and Sinovac select unique strains FY and H07 respectively which were all isolated from Anhui province in South China [36 37 Thus far no vaccine offers effectively prevented EV-A71 illness in HFMD individuals is available. Previously lethal mouse model in EV-A71 illness has been a pivotal evaluation part in the development of EV-A71 vaccines [27 29 33 Abametapir 35 However EV-A71 viral isolates Abametapir from HFMD individuals in northeastern China [38] have not been previously analyzed inside a mouse model or for vaccine development. Our group offers isolated and recognized several circulating EV-A71 strains from hospitalized HFMD children in northeastern China who experienced either severe or slight disease. We identified that these strains are complex recombinant viruses including multiple type A human being enterovirus (HEV) [38]. In the present study we examined and compared the virulence pathological changes and progression induced from the circulating EV-A71 viruses including Changchun (CC Northeast China) and Fuyang (FY South Abametapir China) strains inside a neonatal mouse model. These strains showed different virulence and a series of lethal strains could be used as a tool for vaccine evaluation. Furthermore the EV-A71 vaccine candidate CC063 strain with the highest virulence also offered a broadly cross-neutralizing capacity and safety to neonatal mice from lethal-dose infect with numerous EV-A71 viruses. At the same time the sera of the immunized dams and their pups showed higher neutralization titers against numerous EV-A71 viruses. The lethal challenge and safety in mouse model from circulating main EV-A71 strains and the select vaccine.