Overcoming Maternal Antibody Interference in Swine Influenza: Advancing DNA Vaccine Strateies for Enhanced Immune Protection in Piglets

Authors

• Danh Cong Lai, University of Nebraska-LincolnFollow

First Advisor

Scott McVey

Committee Members

Hiep L. X. Vu, Gustavo Delhon

Date of this Version

7-2025

Document Type

Thesis

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 Science

Under the supervision of Professor David Scott McVey

Lincoln, Nebraska, July 2025

Comments

Copyright 2025, Danh Cong Lai. Used by permission

Abstract

Maternally derived antibodies (MDAs) play a vital role in protecting neonates from infectious diseases, but their presence at the time of vaccination can interfere with vaccine-induced immune responses, thereby reducing vaccine effectiveness. MDA interference has been documented in pigs vaccinated with whole inactivated virus (WIV) vaccines against swine influenza A virus (IAV). In this thesis, we evaluated the efficacy of a lipid nanoparticle encapsulated DNA (LNP-DNA) vaccine against swine IAV in the presence and absence of MDAs, comparing it to a WIV vaccine. In MDA-negative piglets, both the LNP-DNA and WIV vaccines induced strong immune responses and effectively prevented the vaccinated animals from being infected with the homologous IAV strain. However, in MDA-positive piglets, the WIV vaccine failed to trigger significant antibody or T-cell responses and offered no protection against viral shedding or lung damage. In contrast, the LNP-DNA vaccine elicited stronger immune responses in MDA-positive pigs, reduced nasal viral shedding, and prevented lung lesions. These findings demonstrate that the LNP-DNA vaccine overcomes MDA interference, making it a promising strategy for enhancing vaccine efficacy in neonatal animals despite maternal antibody presence.

Advisor: David Scott McVey