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

Abstract

We previously induced protective immune response by oral immunization with yeast expressing the ApxIIA antigen. The ApxI antigen is also an important factor in the protection against Actinobacillus pleuropneumoniae serotype 5 infection; therefore, the protective immunity in mice following oral immunization with Saccharomyces cerevisiae expressing either ApxIA (group C) or ApxIIA (group D) alone or both (group E) was compared with that in two control groups (group A and B). The immunogenicity of the rApxIA antigen derived from the yeast was confirmed by a high survival rate and an ApxIA-specific IgG antibody response (p < 0.01). The highest systemic (IgG) and local (IgA) humoral immune responses to ApxIA and ApxIIA were detected in group E after the third immunization (p < 0.05). The levels of IL-1β and IL-6 after challenge with an A. pleuropneumoniae field isolate did not change significantly in the vaccinated groups. The level of TNF-α increased in a time-dependent manner in group E but was not significantly different after the challenge. After the challenge, the mice in group E had a significantly lower infectious burden and a higher level of protection than the mice in the other groups (p < 0.05). The survival rate in each group was closely correlated to the immune response and histopathological observations in the lung following the challenge. These results suggested that immunity to the ApxIA antigen is required for optimal protection.

Expression and assembly of ApxIIA toxin of Actinobacillus pleuropneumoniae fused with the enterotoxigenic E. coli heat-labile toxin B subunit in transgenic tobacco

“…In particular, serovars producing ApxI and ApxII exotoxins are the most virulent (Chiang et al 2009). Thus, Apx toxins, which have a strong immunogenicity, have been characterized and are the primary focus in the development of a vaccine to protect against A. pleuropneumoniae infection (Tascón et al 1994;Reimer et al 1995;Prideaux et al 1999;Fuller et al 2000;Park et al 2005;Shin et al 2005;Lee et al 2006). …”

Functional Pentameric Formation via Coexpression of the Escherichia coli Heat-Labile Enterotoxin B Subunit and Its Fusion Protein Subunit with a Neutralizing Epitope of ApxIIA Exotoxin Improves the Mucosal Immunogenicity and Protection against Challenge by Actinobacillus pleuropneumoniae

“…Oral immunization and sample collections were conducted as described previously (33,55). Briefly, 5-week-old BALB/c female mice (Charles River Technology through Orient Bio, South Korea) were used throughout this study according to the policy and regulations for the care and use of laboratory animals (Laboratory Animal Center, South Korea).…”

“…Experimental procedures using laboratory animals were approved by the Institutional Animal Care and Use Committee of the Chonbuk National University (approval number CBU 2009-0014) and followed the guidelines suggested by the committee. Control or immunized mice were challenged with A. pleuropneumoniae serotype 2 prepared as described previously (33,55). The immunized mice (n ϭ 10 in each group) were injected intraperitoneally with 200 l of an A. pleuropneumoniae preparation (ϳ1 ϫ 10 8 CFU) or buffer (control).…”

“…First, A. pleuropneumoniae gains access to its host through mucosal surfaces of the respiratory tract. Second, we previously reported that orally administered ApxIIA or an antigenic fragment containing its neutralizing epitopes could induce an immune response against A. pleuropneumoniae infection (26,33,43,55,56). However, improved strategies for efficient antigen presentation and immune responses are still needed for enhanced protection against pathogen infection.…”

Efficacy Evaluation of Combination Vaccine of Recombinant C-Terminal Fragments of ApxIA, ApxIIA and ApxIIIA in Piglets

“…The importance of Apx toxins in protective immunity against PP has been demonstrated in many studies (Haesebrouck et al 2004;Shin et al 2005). The 15 serotypes of APP produce four different Apx toxins including ApxI, ApxII, ApxIII and ApxIV (Zhou et al 2013).…”