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Published on: March 16, 2018
Apoptotic blebs from Leishmania major-infected macrophages as a new approach for cutaneous leishmaniasis vaccination
Roghiyeh Faridnia1, Hamed Kalani2, Hajar Ziaei Hezarjaribi3
1Student Research Committee, Pediatric Infectious Diseases Research Center, Communicable Diseases Institute, Mazandaran University of Medical Sciences, Sari, Iran.
Abstract:
We focused on apoptotic blebs from Leishmania major-infected macrophages as a vaccine for cutaneous leishmaniasis. Apoptosis was induced in L. major-infected J774A.1 cells in order to prepare apoptotic blebs. Test groups of BALB/c mice were immunized with these at doses of 1 × 106, 5 × 106 or 1 × 107 blebs. An immunization control group received Leishmania lysate antigens. The results showed that as the number of apoptotic bodies increased, the lymphocyte proliferation index increased, and this was proportional to IFN-γ level in the test groups. Additionally, the difference of IFN-γ, IL-4, IFN-γ/IL-4 ratio, or total IgG (p < 0.0001) in all groups was statistically significant compared to the negative control group. The highest IFN-γ (514.0 ± 40.92 pg/mL) and IFN-γ/IL-4 ratio (2.94 ± 0.22) were observed in the group that received 1 × 107 apoptotic blebs. The highest levels of IL-4 (244.6 ± 38.8 pg/mL) and total IgG (5626 ± 377 μg/mL) were observed in the immunization control group. Reflecting these data, no lesions were observed in any of the groups vaccinated with apoptotic blebs after 12 weeks. In summary, the use of apoptotic blebs from L. major-infected macrophages is protective against the challenge with L. major in this animal model.
Insights
Apoptotic blebs from Leishmania major-infected macrophages show promise as a vaccine for cutaneous leishmaniasis. Immunization with these blebs protected mice from L. major challenge, demonstrating significant immune responses and absence of lesions.
Area of Science:
- Immunology
- Vaccinology
- Parasitology
Background:
- Cutaneous leishmaniasis remains a significant global health concern.
- Current treatments have limitations, necessitating novel vaccine strategies.
- Apoptotic blebs represent a potential source of immunogenic material for vaccine development.
Purpose of the Study:
- To evaluate the efficacy of apoptotic blebs derived from Leishmania major-infected macrophages as a vaccine against cutaneous leishmaniasis.
- To assess the immune responses induced by different doses of apoptotic blebs in a murine model.
Main Methods:
- Apoptosis was induced in L. major-infected J774A.1 cells to generate apoptotic blebs.
- BALB/c mice were immunized with varying doses of apoptotic blebs (1x10^6, 5x10^6, or 1x10^7).
- Immune responses were measured by lymphocyte proliferation, IFN-γ, IL-4 levels, and total IgG. Mice were challenged with L. major to assess protection.
Main Results:
- Increased apoptotic bleb dosage correlated with higher lymphocyte proliferation and IFN-γ levels.
- Significant differences in IFN-γ, IL-4, IFN-γ/IL-4 ratio, and total IgG were observed compared to the negative control (p < 0.0001).
- The highest IFN-γ and IFN-γ/IL-4 ratio were in the 1x10^7 bleb group; highest IL-4 and IgG were in the Leishmania lysate control group. No lesions were observed in any apoptotic bleb-vaccinated groups after 12 weeks.
Conclusions:
- Apoptotic blebs from L. major-infected macrophages are effective in inducing protective immunity against cutaneous leishmaniasis in a murine model.
- The study demonstrates the potential of apoptotic blebs as a safe and effective vaccine candidate for leishmaniasis.
- Further research is warranted to explore the underlying mechanisms and optimize the vaccine formulation.
