Project Grant R44AI149815

NOVEL G PROTEIN-BASED RSV VACCINE - THE OVERALL OBJECTIVE OF THIS PHASE II SBIR PROPOSAL IS TO DEVELOP A NOVEL G PROTEIN-BASED VACCINE FOR THE PREVENTION OF DISEASE ASSOCIATED WITH LOW RESPIRATORY TRACT INFECTION (LRTI) BY RESPIRATORY SYNCYTIAL VIRUS (RSV). RSV IS A LEADING CAUSE OF LOWER RESPIRATORY ILLNESS IN INFANTS AND YOUNG CHILDREN WORLDWIDE. IT ALSO PLAYS SIGNIFICANT ROLE IN RESPIRATORY ILLNESS IN THE ELDERLY. THERE IS AN URGENT NEED AND COMPELLING REASONS TO DEVELOP RSV VACCINE. PAST AND CURRENT VACCINE DEVELOPMENT EFFORTS ARE MAINLY FOCUSED ON F PROTEIN-BASED RECOMBINANT VACCINES AND LIVE ATTENUATED VACCINES. DESPITE MAJOR EFFORTS FOR SEVERAL DECADES, AN EFFECTIVE RSV VACCINE REMAINS ELUSIVE. RSV G PROTEIN IS RESPONSIBLE FOR VIRAL ATTACHMENT TO HOST CELLS. HOWEVER, ONLY A SINGLE G- BASED VACCINE HAS BEEN STUDIED IN HUMANS TO DATE. IN THE COMPLETED PHASE I SBIR STUDY, WE DEVELOPED A NOVEL RSV VACCINE THAT HAS HIGH SEQUENCE IDENTITY TO TYPE A AND TYPE B VIRUSES. MORE IMPORTANTLY, IT PROVIDED COMPLETE PROTECTION AGAINST LRTI BY TYPE A AND TYPE RSV VIRUSES IN ANIMAL MODELS. THE VACCINE CANDIDATE DID NOT CAUSE VACCINE ENHANCED DISEASE. IN THIS SUBMISSION, WE PROPOSE TO FURTHER DEVELOP THIS PROMISING VACCINE CANDIDATE THROUGH PROCESS AND ANALYTICAL METHOD DEVELOPMENT, EVALUATION OF THE VACCINE CANDIDATE IN MATERNAL IMMUNIZATION AND AGED COTTON RAT MODELS, AND CONDUCTING GLP TOXICOLOGY STUDY. THE PROPOSED WORK WILL PROVIDE A CRITICAL FOUNDATION TO MOVE THE G PROTEIN-BASED RSV VACCINE CANDIDATE TOWARD CLINICAL STUDY.