Fast-Track proposals will be accepted. Direct to Phase II will not be accepted. Number of anticipated awards: 2-3 Budget (total costs): Phase I: $300,000 for up to one year; Phase II: $1,500,000 for up to 3 years. Background Human enterovirus (HEV) infections can cause a variety of conditions including conjunctivitis, hand-foot-mouth disease (HFMD), viral meningitis, viral encephalitis, pericarditis, acute flaccid paralysis (AFP), myocarditis, and possibly type 1 diabetes. While HEV infections are common and generally mild, in some patients HEV infections can cause severe symptoms, including sepsis in neonates, aseptic meningitis in children, and meningitis in adults. EV-D68, EV-71, and coxsackie viruses have been implicated in causing acute flaccid myelitis (AFM) in recent years. Currently, there are no therapeutics available to treat enterovirus infections. There are seven HEV species, each of which includes multiple members, and many of them are known to cause disease. Non-pathogenic strains can evolve to acquire pathogenic potential as well, which can cause difficulty for therapeutic development. One way to address this problem is to focus on broad-spectrum therapeutics, specifically monoclonal antibodies. Project Goal The goal of this topic is to develop broad spectrum prophylactic and therapeutic monoclonal antibody therapeutics against human enteroviruses. The final product can be monoclonal antibodies specific to multiple enteroviruses, a combination of multiple monoclonal antibodies with a narrow specificity, or both. The final product should target different strains of a single family, for example, multiple EV-D68 strains, multiple members in one species (for example Enterovirus A species), or members in multiple species (for example, coxsackie viruses in A and B species). The choice of strains should be medically relevant. Phase 1 activities may include, but are not limited to: • Develop multi-spectrum monoclonal antibodies. • Demonstrate neutralizing activity in vitro against target enteroviruses. • Humanize antibodies if applicable. Phase 2 activities may include, but are not limited to: • Further improve multi-spectrum humanized monoclonal antibodies including but not limited to humanizing monoclonal antibodies and improve potency. • Demonstrate therapeutic potential in animal models. • Develop an efficient delivery system. This SBIR will not support: • Products primarily focused on poliovirus. The design and conduct of clinical trials (see http://www.niaid.nih.gov/researchfunding/glossary/pages/c.aspx#clintrial) for the NIH definition of a clinical trial). For SBIR phase II clinical trial support, see the NIAID SBIR Phase II Clinical Trial Implementation Cooperative Agreement program announcement.