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Foot pad enlargement as a measure of induced immunity to Mycobacterium leprae
Abstract:
Foot pad enlargement (FPE) has been used as a measure of induced immunity to M. leprae, FPE peaked at 2-3 days, but it sometimes persisted for 4 weeks or more. Both as the inducing and eliciting antigen, heat-killed M. leprae were effective, and the optimum dose was about 1 x 10(7) bacilli. Higher doses were associated with flattening of the dose-response curve. Disrupted bacilli were not effective in immunizing mice, but they elicited FPE responses in mice immunized with intact bacilli. Cord factor was not found to have adjuvant activity for M. leprae. In immunization, the intradermal route was confirmed to be more effective than the foot pad route; the subcutaneous route was effective in providing protection against infection. FPE tests were used to investigate the steps of standard purification procedures for M. leprae in armadillo livers. A trypsin-chymotrypsin digestion step was found to be harmful to immunogenicity in one of two experiments.
Insights
Heat-killed Mycobacterium leprae effectively induces immunity, measured by foot pad enlargement (FPE). Optimal immunization involved specific doses and routes, with purification steps potentially impacting immunogenicity.
Area of Science:
- Immunology
- Microbiology
- Infectious Diseases
Background:
- Foot pad enlargement (FPE) is a key indicator of induced immunity to Mycobacterium leprae (M. leprae).
- Understanding optimal immunization strategies is crucial for developing effective leprosy vaccines and treatments.
Purpose of the Study:
- To optimize the use of M. leprae as an antigen for inducing and eliciting immune responses.
- To evaluate different immunization routes and antigen preparations for their efficacy.
- To assess the impact of purification procedures on M. leprae immunogenicity.
Main Methods:
- Utilized heat-killed M. leprae as both inducing and eliciting antigens in a mouse model.
- Administered M. leprae via foot pad, intradermal, and subcutaneous routes.
- Assessed immune response through foot pad enlargement (FPE) measurements.
- Investigated the immunogenicity of disrupted bacilli and the adjuvant activity of cord factor.
- Evaluated the effect of a trypsin-chymotrypsin digestion step during M. leprae purification.
Main Results:
- Heat-killed M. leprae were effective antigens, with an optimal dose of approximately 1 x 10(7) bacilli.
- Higher doses led to a flattened dose-response curve.
- Intradermal immunization was more effective than the foot pad route; subcutaneous route provided protection against infection.
- Disrupted bacilli did not induce immunity but elicited FPE in immunized mice.
- Cord factor lacked adjuvant activity for M. leprae.
- A trypsin-chymotrypsin digestion step during purification was detrimental to immunogenicity in one experiment.
Conclusions:
- Established optimal conditions for using M. leprae in FPE tests for assessing immunity.
- Demonstrated the importance of antigen preparation, dosage, and administration route for effective immunization.
- Highlighted potential issues with specific purification steps affecting the immunogenicity of M. leprae antigens.