Abstract Details
Name
Development of a Chimeric Lassa Virus Glycoprotein Library Using DNA Shuffling for Broadly Reactive Vaccine Antigen Discovery
Presenter
Chandra Bose Prabaharan, University of saskatchewan
Co-Author(s)
Chandra Bose Prabaharan1, Liam Kerr1,3, Shelby Harris1, Diogo Pellegrina1, Vahid Rajabali Zadeh1, Jocelyne Lew1 and Darryl Falzarano1,2,3 1 Vaccine and Infectious Disease Organization (VIDO), University of Saskatchewan 2 Department of Veterinary Microbiology, University of Saskatchewan 3 Department of Biochemistry, Microbiology and Immunology, University of Saskatchewan
Abstract Category
Discovering & Evolving
Abstract
Development of a Chimeric Lassa Virus Glycoprotein Library Using DNA Shuffling for Broadly Reactive Vaccine Antigen Discovery Chandra Bose Prabaharan1, Liam Kerr1,3, Shelby Harris1, Diogo Pellegrina1, Vahid Rajabali Zadeh1, Jocelyne Lew1 and Darryl Falzarano1,2,3 1 Vaccine and Infectious Disease Organization (VIDO), University of Saskatchewan 2 Department of Veterinary Microbiology, University of Saskatchewan 3 Department of Biochemistry, Microbiology and Immunology, University of Saskatchewan Lassa virus exhibits substantial genetic diversity across endemic regions, with multiple circulating lineages complicating the development of broadly protective vaccines. Sequence variation within the viral glycoprotein precursor, the primary target of neutralizing antibodies, limits cross-lineage immune coverage. To address this challenge, we generated a chimeric Lassa virus glycoprotein library using DNA shuffling of representative sequences from multiple lineages. This combinatorial strategy enables exploration of antigenic sequence space while preserving structural compatibility required for proper folding and expression. The shuffled constructs will be expressed and evaluated for antigenic integrity. In parallel, a panel of fifteen neutralizing monoclonal antibodies has been generated and characterized using bio-layer interferometry to define binding kinetics and affinity profiles. These antibodies will serve as antigen-specific molecular binders for downstream screening of the chimeric library. Future studies will employ fluorescence-activated cell sorting of cell surface expressed glycoproteins and bio-layer interferometry to identify variants that retain broad neutralizing antibody recognition. Structural analyses will further define epitope preservation and guide selection of lead immunogens. Promising candidates will be advanced into RNA-based vaccine platforms for immunogenicity evaluation. This work establishes an integrated structural antibody-mediated strategy to engineer and identify broadly reactive Lassa virus vaccine antigens.
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