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

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.

[1]  S. Shin,et al.  Identification of Novel Virulence Determinants in Mycobacterium paratuberculosis by Screening a Library of Insertional Mutants , 2006, Infection and Immunity.

[2]  H. Schwarz,et al.  Immunomodulatory properties of human serum immunoglobulin A: anti‐inflammatory and pro‐inflammatory activities in human monocytes and peripheral blood mononuclear cells , 2005, Clinical and experimental immunology.

[3]  W. C. Losinger Economic impacts of reduced pork production associated with the diagnosis of Actinobacillus pleuropneumoniae on grower/finisher swine operations in the United States. , 2005, Preventive veterinary medicine.

[4]  S. Shin,et al.  Induction of antigen-specific immune responses by oral vaccination with Saccharomyces cerevisiae expressing Actinobacillus pleuropneumoniae ApxIIA. , 2005, FEMS immunology and medical microbiology.

[5]  R. Rappuoli,et al.  Innate Imprinting by the Modified Heat-Labile Toxin of Escherichia coli (LTK63) Provides Generic Protection against Lung Infectious Disease1 , 2004, The Journal of Immunology.

[6]  M. Totsuka,et al.  Candida albicans and Saccharomyces cerevisiae induce interleukin-8 production from intestinal epithelial-like Caco-2 cells in the presence of butyric acid. , 2004, FEMS immunology and medical microbiology.

[7]  M. Smits,et al.  Both ApxI and ApxII of Actinobacillus pleuropneumoniae serotype 1 are necessary for full virulence. , 2004, Veterinary microbiology.

[8]  M. Alric,et al.  Living recombinant Saccharomyces cerevisiae secreting proteins or peptides as a new drug delivery system in the gut. , 2004, Journal of biotechnology.

[9]  S. Shin,et al.  Expression of apxIA of Actinobacillus pleuropneumoniae in Saccharomyces cerevisiae. , 2003, Journal of veterinary science.

[10]  J. Olivo-Marin,et al.  Anti-inflammatory role for intracellular dimeric immunoglobulin a by neutralization of lipopolysaccharide in epithelial cells. , 2003, Immunity.

[11]  M. Minekus,et al.  Recombinant Saccharomyces cerevisiae Expressing P450 in Artificial Digestive Systems: a Model for Biodetoxication in the Human Digestive Environment , 2003, Applied and Environmental Microbiology.

[12]  W. Stok,et al.  Improvement of the systemic prime/oral boost strategy for systemic and local responses. , 2003, Vaccine.

[13]  J. Viret,et al.  Experience with registered mucosal vaccines. , 2003, Vaccine.

[14]  L. Hilgers,et al.  Efficacy of oral administration and oral intake of edible vaccines. , 2002, Immunology letters.

[15]  G. Gerlach,et al.  Construction of an Actinobacillus pleuropneumoniae Serotype 2 Prototype Live Negative-Marker Vaccine , 2002, Infection and Immunity.

[16]  J. Kwang,et al.  The N-Terminal Domain of RTX Toxin ApxI of Actinobacillus pleuropneumoniae Elicits Protective Immunity in Mice , 2002, Infection and Immunity.

[17]  W. Van den Broeck,et al.  Oral immunisation of pigs with fimbrial antigens of enterotoxigenic E. coli: an interesting model to study mucosal immune mechanisms. , 2002, Veterinary immunology and immunopathology.

[18]  D. Pascual,et al.  Fimbriated Salmonella enterica Serovar Typhimurium Abates Initial Inflammatory Responses by Macrophages , 2002, Infection and Immunity.

[19]  D. Silin,et al.  Overcoming immune tolerance during oral vaccination against Actinobacillus pleuropneumoniae. , 2002, Journal of veterinary medicine. B, Infectious diseases and veterinary public health.

[20]  J. Bouvet,et al.  Stimulation of local antibody production: parenteral or mucosal vaccination? , 2002, Trends in immunology.

[21]  P. Langford,et al.  Actinobacillus pleuropneumoniae: pathobiology and pathogenesis of infection. , 2002, Microbes and infection.

[22]  D. Kuritzkes,et al.  Whole recombinant yeast vaccine activates dendritic cells and elicits protective cell-mediated immunity , 2001, Nature Medicine.

[23]  P. Ogra,et al.  Vaccination Strategies for Mucosal Immune Responses , 2001, Clinical Microbiology Reviews.

[24]  M. Schmidt,et al.  Correlations between Antibody Immune Responses at Different Mucosal Effector Sites Are Controlled by Antigen Type and Dosage , 2000, Infection and Immunity.

[25]  M. J. Kennedy,et al.  Identification of Actinobacillus pleuropneumoniae virulence genes using signature-tagged mutagenesis in a swine infection model. , 2000, Microbial pathogenesis.

[26]  C. Chae,et al.  In-situ hybridization for the detection of inflammatory cytokines (IL-1, TNF-alpha and IL-6) in pigs naturally infected with Actinobacillus pleuropneumoniae. , 1999, Journal of comparative pathology.

[27]  G. Dougan,et al.  Structure and mucosal adjuvanticity of cholera and Escherichia coli heat-labile enterotoxins. , 1999, Immunology today.

[28]  C. Prideaux,et al.  Vaccination and Protection of Pigs against Pleuropneumonia with a Vaccine Strain of Actinobacillus pleuropneumoniaeProduced by Site-Specific Mutagenesis of the ApxII Operon , 1999, Infection and Immunity.

[29]  A. Gebert,et al.  Kinetics of particle uptake in the domes of Peyer's patches. , 1998, American journal of physiology. Gastrointestinal and liver physiology.

[30]  T. Standiford,et al.  Alveolar macrophages are required for protective pulmonary defenses in murine Klebsiella pneumonia: elimination of alveolar macrophages increases neutrophil recruitment but decreases bacterial clearance and survival , 1997, Infection and immunity.

[31]  T. Sawada,et al.  Protective efficacy of an affinity-purified hemolysin vaccine against experimental swine pleuropneumonia. , 1997, The Journal of veterinary medical science.

[32]  F. Klis,et al.  Immobilizing proteins on the surface of yeast cells. , 1996, Trends in biotechnology.

[33]  F. Klis,et al.  Yeast expressing hepatitis B virus surface antigen determinants on its surface: implications for a possible oral vaccine. , 1996, Vaccine.

[34]  A. Hensel,et al.  Induction of protective immunity by aerosol or oral application of candidate vaccines in a dose-controlled pig aerosol infection model. , 1996, Journal of biotechnology.

[35]  J. Frey Virulence in Actinobacillus pleuropneumoniae and RTX toxins. , 1995, Trends in microbiology.

[36]  D. Reimer,et al.  Molecular investigation of the role of ApxI and ApxII in the virulence of Actinobacillus pleuropneumoniae serotype 5. , 1995, Microbial pathogenesis.

[37]  R. Pabst,et al.  The immune system of the respiratory tract in pigs. , 1994, Veterinary immunology and immunopathology.

[38]  I. Bathurst Protein expression in yeast as an approach to production of recombinant malaria antigens. , 1994, The American journal of tropical medicine and hygiene.

[39]  R. Lallone,et al.  Evaluation of an orally administered vaccine, using hydrogels containing bacterial exotoxins of Pasteurella haemolytica, in cattle. , 1994, American journal of veterinary research.