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

Author: Danh Cong Lai

Advisor: Scott McVey

Affiliation: University of Nebraska, Lincoln, Nebraska, USA

Background Introduction

Maternally derived antibodies serve as crucial early-life protection for piglets against infectious diseases, including swine influenza A virus (SwIAV). However, these same protective antibodies create significant challenges for vaccination programs by interfering with vaccine-induced immune responses, thereby reducing vaccine effectiveness. This interference has been well-documented with whole inactivated virus (WIV) vaccines against SwIAV, creating an urgent need for innovative vaccination strategies that can overcome MDA interference while maintaining protective efficacy.

The significance of this research extends beyond swine health, as SwIAV poses both agricultural economic impacts and zoonotic risks. Uncomplicated SwIAV infections result in losses exceeding $3 per pig, escalating to over $18 per pig when combined with secondary infections. Additionally, the potential for viral reassortment between swine and human influenza strains makes effective SwIAV control a matter of public health importance.

Fig 1. Transfer of Maternally Derived Antibodies (MDAs). (A) Placental types are categorized based on the arrangement of chorionic villi and the number of tissue layers separating maternal and fetal blood. (EE – endometrial epithelium; BNC – binucleate cell; TNC – trinucleate cell; CT – cytotrophoblast; ST – syncytiotrophoblast). (B) In both humans and rodents, maternal IgG is transferred to the fetus before birth via the syncytiotrophoblast layer of the placenta. (C) After birth, maternal IgG from colostrum is absorbed through the brush border membrane of enterocytes in the neonatal gut.

Materials and Methodology

The researchers conducted an animal study using piglets stratified into MDA-positive and MDA-negative groups, where the positive group was provided colostrum containing SwIAV-specific maternal antibodies immediately after birth. Meanwhile two vaccine platforms were evaluated: a lipid nanoparticle DNA (LNP-DNA) vaccine, and a conventional whole inactivated virus (WIV) vaccine. The LNP-DNA vaccine was prepared by encapsulating DNA plasmids encoding the viral hemagglutinin gene within lipid nanoparticles, while the WIV vaccine followed standard inactivation protocols using formaldehyde treatment. The vaccines were administered to multiple treatment groups based on the previous MDA categorization, and immunological response was measured with hemagglutination inhibition (HI), interferon-gamma ELISpot, real time PCR, and examination of both lung tissue and clinical parameters.

Results

Immunological Responses in MDA-Negative Piglets

Both LNP-DNA and WIV vaccines demonstrated robust immunogenicity in piglets lacking maternal antibodies. Strong antibody responses were observed through HI assays, and both vaccine platforms effectively induced T-cell mediated immunity as measured by interferon-gamma production. These results established baseline vaccine efficacy in the absence of maternal antibody interference.

Critical Findings in MDA-Positive Piglets

The presence of maternal antibodies created a stark divergence in vaccine performance between the two platforms. The WIV vaccine completely failed to induce significant antibody or T-cell responses in MDA-positive piglets, demonstrating the profound suppressive effect of maternal antibodies on conventional vaccination approaches. This finding confirms the well-established challenge of MDA interference with traditional vaccine platforms.

LNP-DNA Vaccine Breakthrough Performance

In contrast to the WIV vaccine, the LNP-DNA vaccine demonstrated remarkable ability to overcome maternal antibody interference. Even in the presence of MDAs, the LNP-DNA vaccine elicited stronger immune responses compared to the failed WIV vaccination. This represents a significant advancement in addressing the longstanding challenge of neonatal vaccination in the presence of maternal antibodies.

Challenge Infection Outcomes

Following experimental challenge with homologous SwIAV, the differential vaccine performance became clinically evident. MDA-positive piglets vaccinated with WIV showed no protection against viral infection, with continued viral shedding and development of lung lesions comparable to unvaccinated controls. Conversely, LNP-DNA vaccinated piglets, regardless of MDA status, demonstrated reduced nasal viral shedding and, importantly, complete prevention of lung lesions. These findings indicate that the LNP-DNA platform not only overcomes immunological interference but also provides meaningful clinical protection.

Pathological Assessment

Histopathological examination of lung tissues provided compelling evidence of vaccine efficacy differences. While WIV-vaccinated, MDA-positive piglets developed characteristic influenza-associated lung lesions, LNP-DNA vaccinated animals maintained normal lung architecture. This histological protection correlates directly with the immunological findings and demonstrates the clinical relevance of overcoming MDA interference.

Conclusion

Lai demonstrated that LNP-DNA vaccines represent a paradigm shift in addressing maternal antibody interference in swine influenza vaccination. Not only were they able to overcome the immunosuppressive effects of maternal antibodies, they also showed protective efficacy against SwIAV infection. This opens new possibilities for protecting vulnerable young animals during critical early-life periods.

This paper utilized the PreciGenome NanoGenerator Flex-M for microfluidic LNP synthesis. Its flow rate control and medium production volume permit reliable LNP synthesis with sufficient scalability for varied animal models.

For further details, check out the link to the article here:

https://digitalcommons.unl.edu/vetscidiss/35/