New RSV Vaccines with Improved Safety and Efficacy

Project Summary Respiratory syncytial virusRSVinfectsmillion people and causes substantial mortality annually worldwideThere is no licensed RSV vaccineClinical trials of alum adjuvantedformalin inactivated whole RSVFI RSVvaccine caused vaccine enhanced respiratory disease during epidemic seasonwhich resulted in hospitalizations and two deathsIt is essential that an effective and safe RSV vaccine not induce vaccine enhanced diseaseVEDupon the immunized person s exposure to live RSVCurrently licensed adjuvants cannot prevent or reverse RSV VED in animalsOur studies demonstrate that virus like particleVLPvaccines presenting RSV F proteinsF VLPconfer protection against RSV by controlling lung viral replication without causing detectable VEDIn additionour preliminary data reveals that split RSV is safer than inactivated whole FI RSVand that certain Toll like receptorTLRagonist combination adjuvants further improve split RSV vaccine efficacy and safety by preventing any residual VED responseDuring this STTR phaseprojectwe will assess the efficacy and safety of two promising novel RSV vaccine candidates in mouse and cotton rat preclinical animal modelsThe first candidate is an RSV F VLP vaccine formulated as a standalone agent or in combination with split RSV vaccineWe hypothesize that it may be possible to boost efficacy by combining these two RSV immunogens without compromising safetyOur second candidate is a split RSV vaccine administered with VED preventing TLR agonist adjuvantsWe have established rigorous methods for evaluating RSV vaccine safetyefficacyand monitoring detailed innate and adaptive immunological responses in animal modelsIn Aimof this projectwe will focus on testing our newly developed F VLP and split RSV vaccines standalone or in combinations for efficacy and safety in mouse modelsWe will also determine whether split RSV vaccine in combination with low dose TLR agonists will improve the efficacy of RSV vaccines while preventing VED in miceThe goal of aimis to investigate the immunogenicityefficacyand pulmonary disease of new RSV vaccine combinationsSplit RSVF VLPin cotton rats after vaccination and challengeWe shall undertake additional studies of vaccine candidates with the most attractive efficacy and safety profiles in aged animal models during a PhaseSTTR project Narrative Respiratory syncytial virusalso called RSVcan cause very serious diseasehospitalizations in intensive careand even death in vulnerable populationssuch as new born babiesinfantsand the elderlyThere is no safe and effective vaccine for RSVDuring this projectour team will test two promising innovative RSV vaccines