Screening And Evaluation Of Broad-spectrum And High-Neutralizing Antibody Against Respiratory Syncytial Virus F Protein

Respiratory syncytial virus(RSV)is the most common pathogen for lower respiratory tract disease affecting infants,the elderly and immunocompromised individuals around the world.All children aged less than 2 years were almost infected by RSV.About 5%of infants are hospitalized for RSV infection every year,which brings global health care a heavy financial burden.So far,there is no safe and effective RSV vaccines on the market.Palivizumab(Palivizumab(?))is the only drug approved by US FDA for protection against RSV.But due to its high costs,limited therapeutical effect and m?Ltiple inoc?Lations needed to be taken,it is only applied to high risk of infants.it is significant that RSV neutralizing monoclonal antibodies with highly efficient and low costs are developed to protect infants from RSV infection.RSV F and G protein is the main target stim?Lating protective immune response.Protein G has an extensive antigenic variation between RSV subgroup A and B,but neutralizing antibodies induced by highly conserved F protein can inhibit RSV A and B infection.Therefore,protein F is viewed as the main target of developing RSV neutralizing antibodies and vaccines.The m?Ltiple immunizations program based on nucleic acid vector was used to immunize Balb/c mice.10 of anti-RSV F mAbs were obtained through the several rounds of antibody screening,which were identified as broad-spectrum and highly efficient neutralizing mAbs specially recognizing RSV A and B prefusion F by RSV reactivity and neutralization assay.According to comparison of the CDR sequences of the novel mAbs with those of representative mAbs recognizing sites previously reported,these mAbs were preliminarily classified into four types(5B11?6B2?7G5 and 10F3).RSV antibody cross-blocking assay was performed to research the sites of F protein four types of mAbs binding,implying that 5B11?6B2 and 7G5 may recognize the novel epitopes on F protein,while 10F3 may bind Site(?)on the top of F protein,similar to 5C4.In addition,the evaluation of their prophylactic potential in mice model demonstrated that 5B11?6B2 and 7G5 had a protective effect comparable with 5C4 at the same dose(1.5mg/kg).Above all,5811?6B2 and 7G5 are expected to display 5C4 and developed as a new generation of broad-spectrum,highly efficient and prophylactic mAbs.The new antibodies and these antigenic sites laid the foundation for the development of future RSV drugs with high efficacy and low costs,and also provided guidance for molec?Lar design of RSV vaccines.