Bunyavirus and Picornavirus Pandemic Pathogen Preparedness (BP4) Center

Project Summary Pathogenic picornaviruses and bunyaviruses have an enormous impact on public health worldwide, and our understanding of mechanistic correlates of immunity for members of these virus families is limited. Because of the diversity of viruses in these families, it is unlikely medical countermeasures (such as vaccines and antibodies) can be developed ahead of time for each one of these viruses, therefore a prototype pathogens approach is warranted. We have assembled a highly interdisciplinary consortium of leading investigators in the field of picornavirus and bunyavirus virology, immunology, vaccine biology and antibody sciences to study the mechanistic correlates of immunity to prototype pathogens for these families, and then apply the principles we learn with the prototype pathogens to different pathogenic viruses in those families that are antigenically distinct. All five Research Projects (RP) in the Center focus on developing strategies effective against all pathogenic members of a group of viruses, picornaviruses, hantaviruses, and diverse arenaviruses. RP1 focuses on innovative vaccine strategies for picornaviruses (enterovirus D68, enterovirus A71, echovirus 11 and rhinovirus C types), RP2 focuses on human anti-picornavirus monoclonal antibodies, RP3 focuses on novel vaccine candidates for hantaviruses, RP4 focuses on human mAbs for Sin Nombre, Andes and Hantaan hantaviruses, and RP5 proposes studies on arenavirus vaccines and antibodies, with LCMV as an initial prototype for study. A unique aspect of this Center is that it includes full complementary research projects for both vaccine and mAbs, which are the two most well-studied countermeasures that provide complete pre- or post-exposure protection against virus infections. The advanced level of certain preliminary findings in the work described in the RPs is a major strength and advantage of our Center. There has relatively little significant progress over the last decade in the development of vaccines or postexposure therapies for picornaviruses or bunyaviruses. Preventive vaccines would have utility for the public during local or large-scale outbreaks, for laboratory workers, for first responders or individuals at high-risk exposure, and for certain travelers or military personnel. In the case of a biological attack or natural outbreak, however, a preventative or postexposure antibody treatment would be the most practical approach for rapid deployment and has the advantage that antibodies can be used in any age or health condition, including the immunocompromised. perform pivotal studies that will facilitate the development of products used for the prevention and treatment of Nipah and Hendra infections. The cooperation among the paired vaccine + mAb RPs, the Administrative Core, the sample acquisition, structural biology, and vaccine technology cores is built into the Center by design, as all components work together to provide broadly effective candidate countermeasures. Quality system data management will be employed in both the preparation of advanced stage test articles and in the conduct of animal studies.