Overcoming Immune Tolerance During Oral Vaccination Against Actinobacillus pleuropneumoniae

Abstract

In the preliminary study mice were vaccinated orally with Actinobacillus pleuropneumoniae microsphere oral vaccine. The lung and eye mucous membranes of these mice did not contain increased immunoglobulin A (IgA) following the initial oral vaccination, possibly through antibody persistence and the phenomenon of immune exclusion. A similar tendency was found for serum IgG. However, after the second vaccination, IgA still did not increase significantly, which could be attributed to immune suppression due to the possibility of the intestine inducing immune tolerance. Only the third vaccination overcame this effect and increased the level of IgA. In order to achieve a high systemic and local immune response this study attempted to overcome the initial tolerance to oral vaccination by using temporary immunosuppression, increasing antigen dose, and prolonging vaccine influence. Triamcinolone, used in the later productive phase of the immune response after the first and second vaccinations, but restricted in the inductive phase of the second and third vaccinations, could disable immune tolerance. Suppression of antibody production before the next induction of the immune response by an oral vaccine combined with suppression of cell-suppressor activity led to the creation of systemic immunity with the possibility of high levels of A. pleuropneumoniae growth inhibition. Increased antigen doses or durable consumption of antigen could overcome immune exclusion of antigen by primary antibodies. Even very low doses of vaccine (4.5 mg) could induce a primary immune response, and a dose increased by 10-fold for the second vaccination could overcome tolerance and maintain high systemic immunity. Chronic consumption of oral vaccine led to benefits in the quantity of local (not systemic) antibodies. The outcomes of the study can be adapted for practical oral immunization of pigs.

Induction of antigen-specific immune responses by oral vaccination withSaccharomyces cerevisiaeexpressingActinobacillus pleuropneumoniaeApxIIA

“…[12,14,15]. The targeting and induction of specific local immune mechanisms in mucosal immunity is most effectively achieved by a direct application of antigens to the mucosal surfaces, resulting in the optimal initiation of humoral and/or cell‐mediated immune responses [13,14,18]. In addition, mucosal application of a vaccine can also effectively induce a systemic immune response [18].…”

“…In addition, mucosal application of a vaccine can also effectively induce a systemic immune response [18]. The successful initiation of mucosal immunization depends on not only the effective delivery of antigen to the mucosal immune induction site but also a choice of regime and the amount of antigens to induce protective responses at the desired mucosal site and preferably systematically as well [11,13,17]. Therefore, the amount of antigen and the immunization intervals were determined through our preliminary experiments.…”

“…It is therefore desirable to develop vaccination strategies that lead to mucosal immune responses. Ideally, a vaccine administered orally elicits mucosal protection as well as systemically favors an immune responses [10–13]. Important roles of specific immunoglobulin A (IgA) in natural and experimental infections had been focused [9].…”

“…Important roles of specific immunoglobulin A (IgA) in natural and experimental infections had been focused [9]. Also, it is well documented that secretory IgA (sIgA) antibodies found in secretions are produced locally by plasma cells in the respiratory mucosa, and such antibodies may protect the host from both colonization and disease [9,13]. sIgA functions to prevent the adsorption of pathogens or their toxic products at the mucosal epithelium [14].…”

Enhancement of protective immune responses by oral vaccination with Saccharomyces cerevisiae expressing recombinant Actinobacillus pleuropneumoniae ApxIA or ApxIIA in mice

“…Immunoglobulin A (IgA) is the most abundant Ig isotype present in the mucosal tissue during infection and is crucial as a first line of defense. The main role of secretory IgA in oral immunization [8,22] is to protect the host by inhibiting pathogen attachment, immune exclusion, and facilitating the clearance of toxic products [37]. IgA may also function in lung defense by influencing the trafficking of specific cells through the common mucosal immune system [19].…”