First Advisor
Hiep L. X. Vu
Committee Members
Hiep Vu, Dustin Loy, Eric Weaver
Citation
A thesis presented to the faculty of the Graduate College at the University of Nebraska in partial fulfillment of requirements for the degree of Master of Science
Major: Veterinary Sciences
Under the supervision of Professor Hiep L. X. Vu
Lincoln, Nebraska, May 2025
Abstract
The two primary challenges in developing vaccines against swine influenza A virus (IAV-S) are the continuous viral evolution and vaccine-associated enhanced respiratory disease (VAERD). Current vaccine strategies share a common limitation: the significant time required for licensing updated vaccines. Moreover, the strain selection for vaccine updates depends entirely on predictions, raising the risk that chosen strains may not match circulating viruses. Such mismatches not only reduce vaccine efficacy but also risk exacerbating disease severity through VAERD. Here, in this thesis, we developed and evaluated a novel DNA-based vaccine platform designed to address the need for rapid updates in response to circulating influenza strains. Specifically, we encapsulated DNA within lipid nanoparticles (LNP-DNA), aiming to enhance DNA stability and promote cellular uptake, advantages not typically achievable with conventional DNA vaccination. In pigs, we demonstrated that a single immunization with LNP-DNA elicited robust antibody responses against the homologous challenge infection with the H1N1-pdm09 virus. Importantly, following challenge with a heterologous challenge with the H1N2-d1a we observed pulmonary eosinophilic infiltration in pigs vaccinated with an adjuvanted the protein-based vaccine. In contrast, pigs vaccinated with the LNP-DNA-based vaccine did not show the eosinophilia. The observation suggests that pulmonary eosinophilia is associated with pigs exhibiting VAERD. These findings provide direct evidence that the same vaccine antigen can produce significantly different outcomes, ranging from protective immunity to disease enhancement, depending on the delivery platform used. Overall, the LNP-DNA platform offer as a promising approach for timely vaccine updates and as an effective strategy to overcome VAERD.
Advisor: Hiep L. X. Vu
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Copyright 2025, The Nguyen. Used by permission