Development of a cross-protective HRV vaccine

ABSTRACTHuman rhinovirusesHRVare the leading cause of common colds and virus induced exacerbation of asthma and chronic pulmonary diseasesIn additionHRV can cause severe lower respiratory tract infections in childrenthe elderlyand immune compromised patientsThe economic burden of HRV is estimated to be at least $B each year in the US in terms of direct medical expenses and lost work and productivityA reduction in the rate and severity of common colds would greatly reduce our healthcare expenses and improve the quality of life for millions of individualsInfection with HRV stimulates antibodies that prevent re infection with one specific virushoweverthe immune response is highly serotype restricted and directed against only the homologous virusThe large numbers of serotypes and the serotype restricted immune responses have complicated the design of HRV vaccinesBMI previously produced a set of ten HRV A antigens that stimulate cross serotype neutralizing antibodies using a rational antigen design approach that involves engineering immune dampening mutations into epitopes that stimulate serotype restricted antibodiesExtensive efforts to develop a VLP based vaccine encountered complications with purificationWe have recently succeeded in engineering highly replicative HRVrecombinantsThis breakthrough improves the feasibility of the approach by de risking downstream manufacturing processesIn this applicationwe propose to increase the complexity of the mutations in the recombinant virus to target additional strain restricted sites in an effort to produce an improved antigenIn additionwe plan to assess methods for inactivating the purified virus for development of the first human rhinovirus vaccine NARRATIVEHuman rhinovirusesHRVare the leading cause of common colds and virus induced exacerbation of asthma and chronic pulmonary diseasesIn additionHRV can cause severe lower respiratory tract infections in childrenthe elderlyand immune compromised patientsThe economic burden of HRV is estimated to be at least $B each year in the US in terms of direct medical expenses and lost work and productivityA reduction in the rate and severity of common colds would greatly reduce our healthcare expenses and improve the quality of life for millions of individualsIn previous studieswe designed HRVrecombinants bearing mutations that lead to the stimulation of cross neutralizing antibodiesWe propose to more fully develop the reverse engineered viruses to include more complex mutations to increase the number of serotypes that can be neutralized in an effort to produce the first human rhinovirus vaccine