Azad K Kaushik
University of Guelph, Canada
Title: Exceptionally long CDR3H of bovine scFv antigenized with BoHV-1 B-epitope generates specific immune response against the targeted epitope
Biography
Biography: Azad K Kaushik
Abstract
Some bovine antibodies are the largest known to exist in a species because of an exceptionally long CDR3H (up to 61 amino acids). The exceptionally long CDR3H is encoded by an unusually long germline IGHD genes together with insertion of “a” nucleotide rich conserved short nucleotide sequence at the IGHV-IGHD junction. The atypical CDR3H confers unique “knob and stalk” structural architecture where configurational diversity of the knob is generated by variable intra-CDR3H disulfide bridges. The knob is separated by solvent exposed stalk formed by anti-parallel beta strands. Structural features of the bovine antibody with an exceptionally long CDR3H can be exploited for the development of new therapeutics, vaccines and drugs. In this context, I will discuss structural optimization of bovine scFvs to enhance viral neutralization potency. An evidence for subtle influence of framework residues on viral neutralization functions will be presented. I will discuss our recent data on bovine scFv with exceptionally long CDR3H antigenized with B-epitope that induces specific immune response. To this end, we first developed functional scFv with an exceptionally long CDR3H followed by grafting of a B-epitope (gC156) from bovine herpes virus-1 into the CDR3H. The grafted B-epitope in bovine scFv with an exceptionally long CDR3H sustained configuration similar to the native epitope. The antigenized scFv (gC156scFv1H12) induced higher antibody response as compared to free recombinant gC156 fragment in the calves. To conclude, antigenization of bovine scFv with an exceptionally long CDR3H provides a novel approach to developing new vaccines for humoral protection against infectious agents.
