Sole-Source Award Task A60 - Mouse Models for Polio and Coxsackie Viruses

Introduction The National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), of the Department of Health and Human Services (DHHS) plays a major role in developing medical products for human viral diseases other than AIDS. The NIAID, Division of Microbiology and Infectious Diseases (DMID) has a requirement to provide support to the research community for testing therapeutics in mouse models for polio and coxsackie viruses through establishment of mouse models of these viruses. Antiviral agents against poliovirus will aid in the ongoing polio eradication effort and will provide a means to combat potential accidental or intentional exposures of poliovirus after eradication. Coxsackie viral infection is a leading cause of both acute and chronic myocarditis. Currently, there are no effective therapeutics or vaccines for coxsackie virus. These two models together will provide a means to evaluate broad spectrum therapeutics against viruses, in particular against enteroviruses. Background: The NIAID, DMID awarded a task order contract to Southern Research Institute (SRI) in 2012 to provide compound screening and preliminary evaluation of therapeutic candidates with standardized mouse models to identify new compounds with broad antiviral activity against enteroviruses. This original award was a competitive acquisition. Listed below are facts that support the award of a follow-on sole source award: - 1) The IDIQ basic contract scope of work did not require specific expertise in polioviruses. As a result, there is a definitive lack of experience among the IDIQ contractor pool. - 2) The first Task Order solicitation to develop a small animal model for development and testing antivirals for enteroviruses failed to receive a single application. - 3) A follow-on solicitation received only 3 proposals; SRI was the only contractor with expertise in poliovirus. - 4) The use of ifnr transgenic mice was a requirement for completion of the task order. SRI had the licensure agreement with a Japanese institute that developed the mice. - 5) It is time-consuming to establish breeding colonies of transgenic mice (so that they can be bred further to produce enough animals to conduct studies). SRI has breeding stocks of these mice, which resulted in a cost savings to the Government. - 6) This task order is part of NIAID's contribution to the Polio Antiviral Initiative, an interagency and international effort involving NIAID, the Food and Drug Administration , the Centers for Diseases Control and Prevention and the World Health Organization (more information at http://www.polioeradication.org/Research/Antivirals.aspx). The development of antiviral agents against poliovirus will aid in the ongoing polio eradication effort and will provide a means to combat potential accidental or intentional exposures of poliovirus after eradication. The current task order expired in January 2014; therefore it is in the best interests of the Government, the scientific community, and the public to continue this important work The scope of work is to evaluate antiviral agents in CD155 transgenic mouse models (carrying human poliovirus receptor, CD155) in ifnar1-/- background (PVR-ifnar-/-, Kuss, Etheredge, and Pfeiffer, PLoS Pathog 2008, 4: e1000082-, and Kuss, et al., Science 2011, 334: 249 DOI: 10. 1126/Science 1211057); and establishing a polio mouse model in PVR transgenic mice in wild type genetic background (cPVR mouse, Crotty et. al, J. Gen Virol. 2002, 83: 1707-1720) to compare that with PVR ifnar1-/- model. An ideal model should resemble human polio pathogenesis as closely as possible and can be easily manipulated, exhibit high sensitivity of infection and in a highly reproducible manner. Poliovirus strains to be used are Mahony1 for type 1 and MEF-1 for type 2 polioviruses that will be provided by the government. For coxsackie virus, NIAID is interested in testing antivirals using CVB 3 virus for myocarditis and pancreatitis indications in the C57BL/6J mouse model (Kemball, Harkins, and Whitton, 2008, J. Virol 82(9): 433104342). In addition, NIAID is interested in establishing a coxsackie virus model using Balb/c mice with CVB4 as the test viral strain and comparing it with CVB3/C57BL/6J model. DMID has determined that Southern Research Institute is the only responsible source to evaluate antiviral agents using PVR ifnar-/- mice and for poliovirus and using coxsackie virus B3 in C57B/J6 mice. Alternative models shall be assessed and if they perform satisfactorily, antiviral evaluations may be performed in these new models. The Contractor is responsible for acquiring all mice strains including Material Transfer Agreements with relevant parties. Period of performance: February 26, 2014 to August 25, 2015.