Lipid nanoparticle-encapsulated DNA vaccine induces balanced antibody and T-cell responses in pigs with maternally derived antibodies.

UNLABELLED: 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). This study 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 with maternal antibodies.

IMPORTANCE: Maternally derived antibody (MDA) interference is a major obstacle to developing effective vaccines for neonates. In pigs, MDAs significantly impair immune responses to a whole-inactivated virus vaccine. Here, we show that vaccination with a lipid nanoparticle (LNP)-encapsulated DNA vaccine can partially overcome MDA interference. These findings underscore the potential of the LNP-DNA vaccine as a viable strategy for effectively immunizing MDA-positive populations. Additionally, LNP-DNA vaccination in young pigs provides a valuable model for exploring the immunological mechanisms behind MDA-mediated suppression of vaccine-induced immunity.