Immune responses in mice to Mycobacterium avium subsp. paratuberculosis following vaccination with a novel 74F recombinant polyprotein

Summary Johne's disease (JD) is a chronic infectious disease of ruminants caused by Mycobacterium avium subsp. paratuberculosis (MAP). Here, we report the cloning and expression of a 74 kDa recombinant polyprotein (Map74F) and its protective efficacy against MAP infection in mice. Map74F was ge...

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Veröffentlicht in:Vaccine 2008-02, Vol.26 (9), p.1253-1262
Hauptverfasser: Chen, Li-Hsuen, Kathaperumal, Kumanan, Huang, Ching-Juo, McDonough, Sean P, Stehman, Susan, Akey, Bruce, Huntley, John, Bannantine, John P, Chang, Chao-Fu, Chang, Yung-Fu
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container_end_page 1262
container_issue 9
container_start_page 1253
container_title Vaccine
container_volume 26
creator Chen, Li-Hsuen
Kathaperumal, Kumanan
Huang, Ching-Juo
McDonough, Sean P
Stehman, Susan
Akey, Bruce
Huntley, John
Bannantine, John P
Chang, Chao-Fu
Chang, Yung-Fu
description Summary Johne's disease (JD) is a chronic infectious disease of ruminants caused by Mycobacterium avium subsp. paratuberculosis (MAP). Here, we report the cloning and expression of a 74 kDa recombinant polyprotein (Map74F) and its protective efficacy against MAP infection in mice. Map74F was generated by the sequential linkage of the ORFs of the ∼17.6-kDa C-terminal fragment of Map3527 to the full-length ORF of Map1519, followed at the C-terminus with ∼14.6-kDa N-terminal portion of Map3527. Mice immunized with Map74F had a significant IgG1 response but not IgG2a. In immunized animals, the IgG1/IgG2a ratio increased until 4 weeks after MAP challenge. The ratio decreased from 8 weeks indicating a shift to a Th1 response. Antigen specific IFN-γ response, CD3+ and CD4+ T cells increased significantly in immunized mice. Following challenge, MAP burden was significantly lower in liver, spleen and mesenteric lymph nodes of immunized animals compared to control animals indicating protection against MAP infection. This was further evident by the improved liver and spleen pathology of the immunized animals, which had fewer granulomas and lower numbers of acid-fast bacilli. Results of this study indicated that immunization of mice with Map74F protected mice against MAP infection.
doi_str_mv 10.1016/j.vaccine.2007.12.014
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Here, we report the cloning and expression of a 74 kDa recombinant polyprotein (Map74F) and its protective efficacy against MAP infection in mice. Map74F was generated by the sequential linkage of the ORFs of the ∼17.6-kDa C-terminal fragment of Map3527 to the full-length ORF of Map1519, followed at the C-terminus with ∼14.6-kDa N-terminal portion of Map3527. Mice immunized with Map74F had a significant IgG1 response but not IgG2a. In immunized animals, the IgG1/IgG2a ratio increased until 4 weeks after MAP challenge. The ratio decreased from 8 weeks indicating a shift to a Th1 response. Antigen specific IFN-γ response, CD3+ and CD4+ T cells increased significantly in immunized mice. Following challenge, MAP burden was significantly lower in liver, spleen and mesenteric lymph nodes of immunized animals compared to control animals indicating protection against MAP infection. 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Here, we report the cloning and expression of a 74 kDa recombinant polyprotein (Map74F) and its protective efficacy against MAP infection in mice. Map74F was generated by the sequential linkage of the ORFs of the ∼17.6-kDa C-terminal fragment of Map3527 to the full-length ORF of Map1519, followed at the C-terminus with ∼14.6-kDa N-terminal portion of Map3527. Mice immunized with Map74F had a significant IgG1 response but not IgG2a. In immunized animals, the IgG1/IgG2a ratio increased until 4 weeks after MAP challenge. The ratio decreased from 8 weeks indicating a shift to a Th1 response. Antigen specific IFN-γ response, CD3+ and CD4+ T cells increased significantly in immunized mice. Following challenge, MAP burden was significantly lower in liver, spleen and mesenteric lymph nodes of immunized animals compared to control animals indicating protection against MAP infection. This was further evident by the improved liver and spleen pathology of the immunized animals, which had fewer granulomas and lower numbers of acid-fast bacilli. Results of this study indicated that immunization of mice with Map74F protected mice against MAP infection.</abstract><cop>Netherlands</cop><pub>Elsevier Ltd</pub><pmid>18243427</pmid><doi>10.1016/j.vaccine.2007.12.014</doi><tpages>10</tpages></addata></record>
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subjects Allergy and Immunology
Animals
Antibodies, Bacterial - blood
Bacterial Vaccines - administration & dosage
Bacterial Vaccines - immunology
Cattle
CD3 Complex - metabolism
CD4 Antigens - metabolism
Female
Immunization
Immunoglobulin G - blood
Interferon-gamma - biosynthesis
Johne's disease
Mice
Mice, Inbred C57BL
Mycobacterium avium
Mycobacterium avium subsp. paratuberculosis - immunology
Paratuberculosis
Paratuberculosis - immunology
Paratuberculosis - microbiology
Paratuberculosis - prevention & control
Polyproteins
Polyproteins - administration & dosage
Polyproteins - chemistry
Polyproteins - genetics
Polyproteins - immunology
Recombinant Proteins - administration & dosage
Recombinant Proteins - chemistry
Recombinant Proteins - genetics
Recombinant Proteins - immunology
Ruminantia
T-Lymphocytes - immunology
Vaccination
Vaccine trials
title Immune responses in mice to Mycobacterium avium subsp. paratuberculosis following vaccination with a novel 74F recombinant polyprotein
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