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Introduction
Immunization of pigs is essential for productivity and animal welfare. Although injectable vaccines are more common, oral vaccines have emerged as a promising alternative, not only for their ease of mass administration and reduced stress but also for their ability to modulate the mucosal immune system, a key barrier against many enteric and respiratory pathogens.
Historical Background and Challenges
Oral vaccination in pigs is not new. A live attenuated oral vaccine against Classical Swine Fever (CSF), tested in pigs and wild boars, provided protection against challenge without shedding of the vaccine strain. The use of palatable bait formulations reinforces the feasibility of this route to immunize large populations, including wild animals, which may be a strategy for field disease control (Chenut et al., 1999).
On the other hand, oral vaccination still faces challenges. While oral immunization is preferable for inducing intestinal IgA, its field efficacy can be inconsistent due to the degradation of labile components, such as antigens exposed to the gastrointestinal tract (pH, enzymes, maternal antibodies). To overcome this, technological innovations that ensure antigen stability and protection are needed, as demonstrated in the examples below.
This text explores the fundamentals of mucosal immunity in pigs, the Common Mucosal Immune System (CMIS), the potential of oral immunization against respiratory and enteric pathogens, and the technological advances that help overcome its limitations.
Mucosal Immunity and the CMIS
The Common Mucosal Immune System (CMIS) describes the functional interconnection between mucosal sites. The mucosae (gastrointestinal, respiratory, and reproductive tracts) are the main entry points for pathogens in pigs. The Mucosa-Associated Lymphoid Tissue (MALT), with its specialized components (GALT in the gut and BALT in the bronchi), initiates local immune responses. The activation of T and B lymphocytes by antigen-presenting cells (APCs) leads to the proliferation of effector and memory cells. The migration of immune cells to other mucosal sites is guided by lymphocyte homing mechanisms (Figure 1), allowing antigens administered orally or intranasally to induce immune responses in distant mucosae, such as the nasal, tracheal, intestinal, oral, and vaginal surfaces. Secretory immunoglobulin A (sIgA) is one of the main effectors, neutralizing pathogens in the lumen. However, the efficacy of vaccination depends on the magnitude, location, specificity, and isotype of the antibody responses (Guevarra et al., 2021; Wilson & Obradovic, 2015). A study on PRRSv demonstrated that oral immunization induced IgA in both oral and vaginal mucosae, reinforcing the systemic impact of oral vaccines on mucosal immunity (Hyland et al., 2004).
Activation of immune cells in one mucosal site can lead to their migration to other mucosal surfaces
Scheme of activation of the common mucosal immune system by oral vaccine
Oral Vaccines Against Respiratory Pathogens
Oral vaccines are commonly used against gastrointestinal pathogens, mimicking natural infection and stimulating local immunity, as seen with commercial vaccines against Escherichia coli and Lawsonia intracellularis. Although historically focused on enteric diseases, oral vaccines are now being developed for more complex pathologies, driven by the CMIS and new technologies.
An oral vaccine against Mycoplasma hyopneumoniae (Mhyo) was developed using SBA-15 silica as an adjuvant, coated with a pH-sensitive polymer that protects the antigen from stomach acids and releases it in the small intestine. This oral vaccine reduced lung lesions by 90% compared to controls, induced IgA in the respiratory tract, and decreased IL-8 levels in lung tissue (Mechler-Dreibi et al., 2021).
Another innovative oral vaccine based on Bacillus subtilis spores against PRRSv induced both humoral and cell-mediated immune responses, as shown by increased IFN-γ and neutralizing antibody levels, along with higher concentrations of specific antibodies and cytokines in pigs (Min et al., 2024).
Similarly, an oral vaccine against PCV2 was developed using recombinant Bacillus subtilis expressing the PCV2 capsid protein. Vaccinated piglets showed elevated levels of PCV2-specific IgA in mucosal tissues of the digestive and respiratory tracts, as well as PCV2-specific IgG in serum, along with increased IL-1β, IL-6, IFN-γ, and β-defensin 2 levels (Zhang et al., 2020).
Conclusion
Oral vaccines represent a promising frontier in swine immunoprophylaxis, with the potential to transform preventive strategies in modern pig production. In addition to ease of large-scale application and reduced animal stress, they stand out for their ability to stimulate mucosal immunity, an important component in defense against both enteric and respiratory pathogens.
Growing evidence shows that with the support of innovative formulation and delivery technologies, it is possible to overcome the challenges of the oral route, such as antigen degradation in the gastrointestinal tract. By positively modulating immune responses, and even the gut microbiome, oral vaccines could become a strategic tool for more efficient, sustainable pig production, aligned with the demands of animal welfare and biosecurity.
