Enhancing control of porcine rotavirus through the identification of candidate B cell epitopes

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Enhancing control of porcine rotavirus through the identification of candidate B cell epitopes

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2020-08

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From the moment piglets are born, their welfare is threatened by rotavirus (RV), a highly prevalent cause of acute diarrheal disease and mortality. Scientists and producers continue to grapple with how to improve vaccine and surveillance strategies to reduce infections. This ongoing challenge is due in part to a lack of information on which genetic changes within RV drive immune escape. The goals of this dissertation are twofold. We first aimed to investigate whether viral presence or detection in feces can be ameliorated by improved timing of prefarrow immunization. Our second aim was to elucidate B cell epitopes (BCEs) on the capsid proteins VP7 and VP4 to identify possible genetic drivers of vaccine immune escape and antigenic diversity. In Chapter 2, a longitudinal study on a commercial farm assessed whether the timing of prefarrow natural planned exposure (NPE) impacts the levels of RV detected in piglets’ feces. RV was continuously detected regardless of the number of NPE doses, and hypothesized that genetic changes at BCEs contribute to immune escape. We pursued this line of inquiry by elucidating BCEs with a bioinformatic approach. In Chapter 3, we validate and apply an in silico method to predict BCEs of RV VP7. In Chapter 4, we predict BCEs on the VP8*, the VP4 cleavage product that mediates host cell attachment. Alanine mutations at two predicted BCEs resulted in lower antisera binding titers, suggesting that the predicted sites were functional in antibody binding. This research provides evidence that computational approaches can yield immunologically-relevant information from RV sequence data alone and provides the first attempt at characterizing antigenic sites of RVB and RVC. Future surveillance efforts that focus on the predicted epitopes could help producers anticipate the accumulation of antigenic distance between vaccine and field strains, which will be crucial for improving vaccines and supporting piglet health.

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University of Minnesota Ph.D. dissertation. August 2020. Major: Veterinary Medicine. Advisors: Cheryl Dvorak, Douglas Marthaler. 1 computer file (PDF); xi, 158 pages.

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Shepherd, Frances. (2020). Enhancing control of porcine rotavirus through the identification of candidate B cell epitopes. Retrieved from the University Digital Conservancy, https://hdl.handle.net/11299/217156.

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