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Updated: Jun 11, 2026
Adjuvant Activity of Mycobacterium paratuberculosis in Enhancing the Immunogenicity of Autoantigens During Experimental Autoimmune Encephalomyelitis
Published on: May 12, 2023
Ovine immune parameters following immunisation against Mycobacterium avium ssp. paratuberculosis using a lipid-based
Sonia Gillan1, Alan D Hughes, Rory O'Brien
1Disease Research Laboratory, Department of Microbiology & Immunology, University of Otago, Dunedin, New Zealand.
Abstract:
Current commercial sheep vaccines against Mycobacterium avium subspecies paratuberculosis (MAP) are based on the use of live or killed cells from avirulent MAP strains. These stimulate a mixed immune response, featuring both antibody-based and cell-mediated immunity, and can only confer partial protection against Johne's disease but do not prevent infection. This study aimed to identify immune responses in sheep following immunisation with a novel lipid-based live-cell vaccine, drawing comparisons against responses observed to a commercial killed-cell vaccine (Gudair). The live vaccine was administered either subcutaneously or intra-peritoneally, as either a single-dose vaccine or in an homologous prime-boost protocol. A single-dose of the live vaccine was found to stimulate a cellular immune response similar to that of single-dose Gudair, but with markedly lower levels of antibody; however, homologous boosting with the live vaccine, by either s.c. or i.p. routes, generated higher levels of MAP-specific antibody. All immunisation regimes tended to decrease the proportion of CD4(+) T cells but increase the proportions of gammadeltaTCR(+) T cells and CD25(+) cells in antigen-stimulated ex vivo blood samples. The CD8(+):gammadeltaTCR(+) T cell ratio, thought to represent a reduced regulatory capacity among T cells responding to MAP, was increased among animals receiving either Gudair or a single i.p. dose of the live vaccine; however, only the Gudair vaccine simultaneously increased the level of lymph node IFNgamma mRNA expression, and this treatment also caused a significant elevation in the IFNgamma:IL-10 (effector:regulatory) cytokine expression ratio. Thus, among these immunisation regimes, the responses generated by a single s.c. dose of the novel live-cell vaccine appeared to selectively target the CMI-based immune profile thought necessary for control of MAP infection; in contrast, homologous prime-boosting with the live vaccine stimulated a mixed immune response similar to that produced by immunisation with Gudair.
Insights
A novel live-cell vaccine for sheep against Mycobacterium avium subspecies paratuberculosis (MAP) shows promise. A single dose stimulates cell-mediated immunity, crucial for controlling Johne
Area of Science:
- Veterinary Immunology
- Vaccinology
- Bacteriology
Background:
- Current sheep vaccines against Mycobacterium avium subspecies paratuberculosis (MAP) offer limited protection against Johne's disease.
- Existing vaccines stimulate a mixed immune response but do not prevent MAP infection.
- There is a need for improved vaccines targeting cell-mediated immunity (CMI) for effective MAP control.
Purpose of the Study:
- To evaluate immune responses in sheep vaccinated with a novel lipid-based live-cell MAP vaccine.
- To compare the novel vaccine's immunogenicity against a commercial killed-cell vaccine (Gudair).
- To investigate the effects of different administration routes (subcutaneous, intraperitoneal) and protocols (single-dose, prime-boost) on immune responses.
Main Methods:
- Sheep were immunised with either the novel live-cell vaccine or Gudair using various routes and protocols.
- Immune responses were assessed by measuring MAP-specific antibody levels and T cell populations (CD4+, gammadeltaTCR+, CD25+) in antigen-stimulated blood.
- Lymph node IFNgamma and IL-10 mRNA expression were quantified to assess effector and regulatory cytokine profiles.
Main Results:
- A single dose of the novel live vaccine induced CMI similar to Gudair but with lower antibody levels.
- Homologous prime-boosting with the live vaccine increased MAP-specific antibody levels.
- All regimes altered T cell profiles, with Gudair and a single intraperitoneal live vaccine dose increasing the CD8+:gammadeltaTCR+ T cell ratio.
Conclusions:
- A single subcutaneous dose of the novel live-cell vaccine selectively induced a CMI profile beneficial for MAP control.
- Homologous prime-boosting with the live vaccine resulted in a mixed immune response comparable to Gudair.
- The novel vaccine demonstrates potential for developing more effective Johne's disease vaccines in sheep.
