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• W2299269844 abstract "Many viruses evade antibody (Ab)-mediated clearance through the presentation of immunodominant, highly variable epitopes, and the masking of conserved ones. It has been proposed that vaccines incorporating peptides that cross-react with conserved epitopes could be used to target the production of Abs that protect against a range of viral isolates. For this thesis the concept of epitope-targeted vaccine design is explored with the model protein hen egg lysozyme (HEL). The goals of the work are to develop peptide markers for murine anti-HEL Abs that can also be used as immunogen to amplify Ab production against target HEL epitopes. Three types of peptides are analyzed: (i) a peptide selected from a phagedisplayed random peptide library (RPL) with the anti-HEL monoclonal Ab D1.3, (ii) peptides identified from RPLs with polyclonal (pc) Abs from the sera of HEL-immunized mice, and, (iii) peptides derived from the linear sequence of HEL. A peptide selected with Dl .3 Ab shares critical binding residues in common with its cognate discontinuous epitope but showed no reactivity with anti-HEL sera. A prime-boost immunization study, in which mice were primed with HEL to produce anti-HEL pcAbs, and boosted with the peptide to amplify the production of Dl .3 or D l .3-like Abs, did not yield crossreactive Abs. Thus, D l .3 Ab may not have been produced in the priming immunization because it is a rare specificity in the immune response to HEL. A peptide marker for an anti-HEL Ab commonly produced amongst mice was identified in a RPL screening with anti-HEL pcAbs. The commonly reactive peptide was also used in ELISPOT analysis to characterize epitope-specific B cell responses to HEL; the peptide-reactive cells represented less than 1% of IgG-producing B cells. The peptide was not recognized by anti-HEL IgG from rabbit, however, emphasizing the limitations of using animal models for developing epitope-targeted vaccines. Lastly, a set of 10mer overlapping HEL peptides showed common patterns of reactivity with different murine antiHEL sera. These findings indicate that common HEL epitopes are targeted amongst mice in the humoral immune response to HEL and that a prime-boost immunization strategy may succeed with a commonly reactive peptide marker. Key Terms: Antibody, Vaccine Design, Epitope, Hen Egg Lysozyme, Phage-displayed random peptide libraries" @default.
• W2299269844 created "2016-06-24" @default.
• W2299269844 creator A5037916342 @default.
• W2299269844 date "2006-01-01" @default.
• W2299269844 modified "2023-09-23" @default.
• W2299269844 title "Analysis of antibody reactivities in lysozyme-immunized mice with peptide ligands: A model for epitope-targeted vaccine design" @default.
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