Hand, foot and mouth disease (HFMD) is a generally mild exanthem in infants and children under 5 years, characterized by a rash and blisters in the mouth. It is caused by several viruses in the enterovirus genus of the Picornavirus family. Enterovirus 71 (EV71) was discovered in California in a severe case of HFMD with neurologic involvement and was subsequently associated with outbreaks throughout Asia and Eastern Europe, and sporadic cases in North America and Western Europe. In 2008 the global pattern of EV71 infections changed dramatically;most importantly, the number of severe cases with morbidity and mortality increased dramatically in China and other areas of Asia. This prompted NIAID to place EV71 on its high priority list of re-emergent infections. Currently there are no vaccines to prevent infection, nor antiviral or immunotherapeutic agents to treat infections. The long-term goals of this project are to develop vaccine candidates using virus-like particle (VLP) technology.
In Aim 1 we propose to generate baculovirus recombinants expressing the EV71 3CD protease and the PI (capsid genes) from 4 genotypes of EV71. The viral proteins self-assemble to form VLPs. We will generate monoclonal antibodies to the VLPs and test their ability to neutralize or cross-neutralize virus infection. We will also examine the prevalence of EV71 antibodies in sera from the general population.
In Aim 2, we will examine the ability of the VLPs to generate maternal antibodies to protect newborns against a lethal challenge of virus. VLPs could provide a safe source of prophylactic vaccine.
EV71 is a remerging virus that is causing severe cases of hand, foot and mouth disease with neurologic damage and death among young children. Currently there are no vaccines to prevent infection, and no antivirals to treat infections. This proposal provides strategies to use VLPs to prevent infection, as has been successfully achieved for papillomaviruses, and to treat infections by cloning human neutralizing antibodies from EV71-specific memory B cells.
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