Human rhinoviruses (HRV) are the leading cause of common colds and virus-induced exacerbation of asthma and chronic pulmonary diseases. In addition, HRV can cause severe lower respiratory tract infections in children, the elderly, and immune-compromised patients. The economic burden of HRV is estimated to be at least $40B each year in the US in terms of direct medical expenses and lost work and productivity. A reduction in the rate and severity of common colds would greatly reduce our healthcare expenses and improve the quality of life for millions of individuals. Infection with HRV stimulates antibodies that prevent re-infection with one specific virus; however, the immune response is highly serotype-restricted and directed against only the homologous virus. The large numbers of serotypes and the serotype-restricted immune responses have complicated the design of HRV vaccines. BMI 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 antibodies. Extensive efforts to develop a VLP-based vaccine encountered complications with purification. We have recently succeeded in engineering highly replicative HRV16 recombinants. This breakthrough improves the feasibility of the approach by de-risking downstream manufacturing processes. In this application, we 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 antigen. In addition, we plan to assess methods for inactivating the purified virus for development of the first human rhinovirus vaccine.
Public Health Relevance Statement: NARRATIVE Human rhinoviruses (HRV) are the leading cause of common colds and virus-induced exacerbation of asthma and chronic pulmonary diseases. In addition, HRV can cause severe lower respiratory tract infections in children, the elderly, and immune-compromised patients. The economic burden of HRV is estimated to be at least $40B each year in the US in terms of direct medical expenses and lost work and productivity. A reduction in the rate and severity of common colds would greatly reduce our healthcare expenses and improve the quality of life for millions of individuals. In previous studies, we designed HRV16 recombinants bearing mutations that lead to the stimulation of cross-neutralizing antibodies. We 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.
Project Terms: Adult; Antibodies; Antibody Response; Antigens; Asthma; asthma exacerbation; base; Blood Circulation; Cell Culture Techniques; Cells; Characteristics; Child; Chronic; Chronic Obstructive Airway Disease; Clinical Trials; Common Cold; Common Cold Virus; Competence; Complex; Control Groups; design; Development; Dose; Economic Burden; Elderly; Engineering; Epitopes; fitness; Formalin; Future; health economics; Healthcare; Hela Cells; Hospitalization; Human; Immune; Immune response; Immunity; Immunization; Immunize; immunogenic; Impairment; improved; Inactivated Vaccines; Individual; Infection; innovation; irradiation; Lead; lead candidate; Literature; Lower Respiratory Tract Infection; Lung diseases; manufacturing process; Medical; method development; Methods; Morbidity - disease rate; Mutation; Neutralization Tests; neutralizing antibody; next generation; Oryctolagus cuniculus; pathogenic virus; Patients; Poliovirus Vaccines; Population; prevent; Process; Production; Productivity; Publishing; Quality of life; receptor; recombinant virus; Recombinants; Resistance; Rhinovirus; Risk; Sampling; Serotyping; Serum; Severities; Site; System; Technology; Testing; Vaccines; Vertebral column; Virus; virus development; Virus-like particle; Work
