Recombinant outer membrane protein Lipl41 from Leptospira interrogans robust immune responses in mice model
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Abstract
Background and Objectives: Leptospirosis is an infectious zoonotic disease that can result in severe complications. It is widespread, especially in hot and humid climates such as the northern region of Iran. The immune responses to leptospirosis are multifaceted. Lipl41 is an outer membrane protein that is expressed during infection and is highly conserved among pathogenic species. This makes it a good candidate for diagnosis and induction of specific immune responses. The aim of the present study was to evaluate immune responses against recombinant Lipl41 in mice.
Materials and Methods: After immunizing of different groups of mice with recombinant Lipl41 (rLipl41), the levels of specific antibodies and cytokine profiles interferon-gamma/ interleukin-4 (IFN-γ/IL-4) were measured.
Results: The results revealed that rLipl41 showed a significant increase in antibody levels compared with the control groups (P< 0.05). Although the level of IL-4 in the groups that received Lipl41 was similar to that in the other control groups, the IFN-γ levels showed a significant increase (P<0.05).
Conclusion: It has been concluded that recombinant Lipl41 protein could strongly stimulate specific immune responses and be considered a potential candidate for vaccine development and diagnostic research.
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2. Evangelista KV, Coburn J. Leptospira as an emerging pathogen: a review of its biology, pathogenesis and host immune responses. Future Microbiol 2010; 5: 1413-1425.
3. Picardeau M. Virulence of the zoonotic agent of leptospirosis: still terra incognita. Nat Rev Microbiol 2017; 15: 297-307.
4. Costa F, Hagan JE, Calcagno J, Kane M, Torgerson P, Martinez-Silveira MS, et al. Global morbidity and mortality of Leptospirosis: A systematic review. PLoS Negl Trop Dis 2015; 9(9): e0003898.
5. Khaki P. Clinical laboratory diagnosis of human Leptospirosis. Int J Enteric Pathog 2016; 4(1): e31859.
6. Sun A-H, Liu X-X, Yan J. Leptospirosis is an invasive infectious and systemic inflammatory disease. Biomed J 2020; 43: 24-31.
7. Yilmaz H, Turhan V, Yasar KK, Hatipoglu M, Sunbul M, Leblebicioglu H. Characteristics of Leptospirosis with systemic inflammatory response syndrome: a multicenter study. Ann Clin Microbiol Antimicrob 2015; 14: 54.
8. Adler B. Vaccines against Leptospirosis. Curr Top Microbiol Immunol 2015; 387: 251-272.
9. Oliveira TL, Grassmann AA, Schuch RA, Seixas Neto AC, Mendonça M, Hartwig DD, et al. Evaluation of the Leptospira interrogans outer membrane protein OmpL37 as a vaccine candidate. PLoS One 2015; 10(11): e0142821.
10. Cullen PA, Haake DA, Adler B. Outer membrane proteins of pathogenic spirochetes. FEMS Microbiol Rev 2004; 28: 291-318.
11. Haake DA, Zückert WR. The Leptospiral outer membrane. Curr Top Microbiol Immunol 2015; 387: 187-221.
12. Lin X, Sun A, Ruan P, Zhang Z, Yan J. Characterization of conserved combined T and B cell epitopes in Leptospira interrogans major outer membrane proteins OmpL1 and LipL41. BMC Microbiol 2011; 11: 21.
13.Feng CY, Li QT, Zhang XY, Dong K, Hu BY, Guo XK. Immune strategies using single-component LipL32 and multi-component recombinant LipL32-41-OmpL1 vaccines against Leptospira. Braz J Med Biol Res 2009; 42: 796-803.
14. Mariya R, Chaudhary P, Kumar AA, Thangapandian E, Amutha R, Srivastava SK. Evaluation of a recombinant LipL41 antigen of Leptospira interrogans serovar canicola in ELISA for serodiagnosis of bovine leptospirosis. Comp Immunol Microbiol Infect Dis 2006; 29: 269-277.
15. Natarajaseenivasan K, Vijayachari P, Sharma S, Sugunan AP, Selvin J, Sehgal SC. Serodiagnosis of severe Leptospirosis: Evaluation of ELISA based on the recombinant OmpL1 or LipL41 antigens of Leptospira interrogans serovar autumnalis. Ann Trop Med Parasitol 2008; 102: 699-708.
16. Soltani MS, Khaki P, Moradi Bidhendi S, Shahhosseiny MH. Molecular characterization of the lipL41 gene of Leptospira interrogans vaccinal serovars in Iran. Arch Razi Inst 2015; 70: 145-150.
17. King AM, Bartpho T, Sermswan RW, Bulach DM, Eshghi A, Picardeau M, et al. Leptospiral outer membrane protein LipL41 is not essential for acute leptospirosis but requires a small chaperone protein, lep, for stable expression. Infect Immun 2013; 81: 2768-2776.
18. Golab N, Harzandi N, Khaki P, Tebianian M, Esmaelizad M. The evaluation of the stability of Lipl41 outer membrane protein expression in fusion with Lep, a small chaperone protein, in Leptospira. Alborz Univ Med J 2021; 10: 491-500.
19. Ambily R, Mini M, Siju J, Vamshikrishna S, Abhinay G, Gleeja VL, et al. Utility of recombinant LipL41 based IgM and IgG ELISA in diagnosis of canine leptospirosis in an endemic area - a study from Kerala, India. Trop Biomed 2019; 36: 654-663.
20. Golab N, Khaki P, Harzandi N, Esmaelizad M, Tebianian M. Expression and purification of the Lipl41, a surface-exposed lipoprotein antigen of pathogenic Leptospira spp. Vet Arh 2020; 90: 297-305.
21. Sun J, Rutherford ST, Silhavy TJ, Huang KC. Physical properties of the bacterial outer membrane. Nat Rev Microbiol 2022; 20: 236-248.
22. Walker SS, Black TA. Are outer-membrane targets the solution for MDR Gram-negative bacteria? Drug Discov Today 2021; 26: 2152-2158.
23. Konovalova A, Kahne DE, Silhavy TJ. Outer membrane biogenesis. Annu Rev Microbiol 2017; 71: 539-556.
24. Hsu S-H, Yang C-W. Insight into the Structure, Functions, and dynamics of the Leptospira outer membrane proteins with the pathogenicity. Membranes (Basel) 2022; 12: 300.
25. Gharakhani M, Faezi Ghasemi M, Khaki P, Esmaelizad M, Tebianian M. Improvement the expression and purification of Loa22: a lipoprotein with OmpA domain from pathogenic Leptospira serovars. Iran J Microbiol 2023; 15: 674-684.
26. Cagliero J, Villanueva SYAM, Matsui M. Leptospirosis pathophysiology: Into the Storm of Cytokines. Front Cell Infect Microbiol 2018; 8: 204.
27. Senavirathna I, Rathish D, Agampodi S. Cytokine response in human leptospirosis with different clinical outcomes: a systematic review. BMC Infect Dis 2020; 20: 268.
28. Fernandes LGV, Vieira ML, Alves IJ, de Morais ZM, Vasconcellos SA, Romero EC, et al. Functional and immunological evaluation of two novel proteins of Leptospira spp. Microbiology (Reading) 2014; 160: 149-164.
29. Novak A, Hindriks E, Hoek A, Veraart C, Broens EM, Ludwig I, et al. Cellular and humoral immune responsiveness to inactivated Leptospira interrogans in dogs vaccinated with a tetravalent Leptospira vaccine. Vaccine 2023; 41: 119-129.
30. Marinho M, Silva C, Lima VMF, Peiró J, Rperri SHV. Citokine and antibody production during murine Leptospirosis. J Venom Anim Toxins Incl Trop Dis 2006; 12: 595-603.
31. Kita M. Role of IFN-gamma in nonviral infection. Nihon Rinsho 2006; 64: 1269-1274.
32. Vernel-Pauillac F, Goarant C. Differential cytokine gene expression according to outcome in a hamster model of Leptospirosis. PLoS Negl Trop Dis 2010; 4(1): e582.
33. Volz MS, Moos V, Allers K, Luge E, Mayer-Scholl A, Nockler K, et al. Specific CD4+ T-cell reactivity and cytokine release in different clinical presentations of Leptospirosis. Clin Vaccine Immunol 2015; 22: 1276-1284.
34. Umthong S, Buaklin A, Jacquet A, Sangjun N, Kerdkaew R, Patarakul K, et al. Immunogenicity of a DNA and recombinant protein vaccine combining LipL32 and Loa22 for Leptospirosis using chitosan as a delivery system. J Microbiol Biotechnol 2015; 25: 526-536.
35. Yan W, Faisal SM, McDonough SP, Chang CF, Pan MJ, Akey B, et al. Identification and characterization of OmpA-like proteins as novel vaccine candidates for leptospirosis. Vaccine 2010; 28: 2277-2283.
2. Evangelista KV, Coburn J. Leptospira as an emerging pathogen: a review of its biology, pathogenesis and host immune responses. Future Microbiol 2010; 5: 1413-1425.
3. Picardeau M. Virulence of the zoonotic agent of leptospirosis: still terra incognita. Nat Rev Microbiol 2017; 15: 297-307.
4. Costa F, Hagan JE, Calcagno J, Kane M, Torgerson P, Martinez-Silveira MS, et al. Global morbidity and mortality of Leptospirosis: A systematic review. PLoS Negl Trop Dis 2015; 9(9): e0003898.
5. Khaki P. Clinical laboratory diagnosis of human Leptospirosis. Int J Enteric Pathog 2016; 4(1): e31859.
6. Sun A-H, Liu X-X, Yan J. Leptospirosis is an invasive infectious and systemic inflammatory disease. Biomed J 2020; 43: 24-31.
7. Yilmaz H, Turhan V, Yasar KK, Hatipoglu M, Sunbul M, Leblebicioglu H. Characteristics of Leptospirosis with systemic inflammatory response syndrome: a multicenter study. Ann Clin Microbiol Antimicrob 2015; 14: 54.
8. Adler B. Vaccines against Leptospirosis. Curr Top Microbiol Immunol 2015; 387: 251-272.
9. Oliveira TL, Grassmann AA, Schuch RA, Seixas Neto AC, Mendonça M, Hartwig DD, et al. Evaluation of the Leptospira interrogans outer membrane protein OmpL37 as a vaccine candidate. PLoS One 2015; 10(11): e0142821.
10. Cullen PA, Haake DA, Adler B. Outer membrane proteins of pathogenic spirochetes. FEMS Microbiol Rev 2004; 28: 291-318.
11. Haake DA, Zückert WR. The Leptospiral outer membrane. Curr Top Microbiol Immunol 2015; 387: 187-221.
12. Lin X, Sun A, Ruan P, Zhang Z, Yan J. Characterization of conserved combined T and B cell epitopes in Leptospira interrogans major outer membrane proteins OmpL1 and LipL41. BMC Microbiol 2011; 11: 21.
13.Feng CY, Li QT, Zhang XY, Dong K, Hu BY, Guo XK. Immune strategies using single-component LipL32 and multi-component recombinant LipL32-41-OmpL1 vaccines against Leptospira. Braz J Med Biol Res 2009; 42: 796-803.
14. Mariya R, Chaudhary P, Kumar AA, Thangapandian E, Amutha R, Srivastava SK. Evaluation of a recombinant LipL41 antigen of Leptospira interrogans serovar canicola in ELISA for serodiagnosis of bovine leptospirosis. Comp Immunol Microbiol Infect Dis 2006; 29: 269-277.
15. Natarajaseenivasan K, Vijayachari P, Sharma S, Sugunan AP, Selvin J, Sehgal SC. Serodiagnosis of severe Leptospirosis: Evaluation of ELISA based on the recombinant OmpL1 or LipL41 antigens of Leptospira interrogans serovar autumnalis. Ann Trop Med Parasitol 2008; 102: 699-708.
16. Soltani MS, Khaki P, Moradi Bidhendi S, Shahhosseiny MH. Molecular characterization of the lipL41 gene of Leptospira interrogans vaccinal serovars in Iran. Arch Razi Inst 2015; 70: 145-150.
17. King AM, Bartpho T, Sermswan RW, Bulach DM, Eshghi A, Picardeau M, et al. Leptospiral outer membrane protein LipL41 is not essential for acute leptospirosis but requires a small chaperone protein, lep, for stable expression. Infect Immun 2013; 81: 2768-2776.
18. Golab N, Harzandi N, Khaki P, Tebianian M, Esmaelizad M. The evaluation of the stability of Lipl41 outer membrane protein expression in fusion with Lep, a small chaperone protein, in Leptospira. Alborz Univ Med J 2021; 10: 491-500.
19. Ambily R, Mini M, Siju J, Vamshikrishna S, Abhinay G, Gleeja VL, et al. Utility of recombinant LipL41 based IgM and IgG ELISA in diagnosis of canine leptospirosis in an endemic area - a study from Kerala, India. Trop Biomed 2019; 36: 654-663.
20. Golab N, Khaki P, Harzandi N, Esmaelizad M, Tebianian M. Expression and purification of the Lipl41, a surface-exposed lipoprotein antigen of pathogenic Leptospira spp. Vet Arh 2020; 90: 297-305.
21. Sun J, Rutherford ST, Silhavy TJ, Huang KC. Physical properties of the bacterial outer membrane. Nat Rev Microbiol 2022; 20: 236-248.
22. Walker SS, Black TA. Are outer-membrane targets the solution for MDR Gram-negative bacteria? Drug Discov Today 2021; 26: 2152-2158.
23. Konovalova A, Kahne DE, Silhavy TJ. Outer membrane biogenesis. Annu Rev Microbiol 2017; 71: 539-556.
24. Hsu S-H, Yang C-W. Insight into the Structure, Functions, and dynamics of the Leptospira outer membrane proteins with the pathogenicity. Membranes (Basel) 2022; 12: 300.
25. Gharakhani M, Faezi Ghasemi M, Khaki P, Esmaelizad M, Tebianian M. Improvement the expression and purification of Loa22: a lipoprotein with OmpA domain from pathogenic Leptospira serovars. Iran J Microbiol 2023; 15: 674-684.
26. Cagliero J, Villanueva SYAM, Matsui M. Leptospirosis pathophysiology: Into the Storm of Cytokines. Front Cell Infect Microbiol 2018; 8: 204.
27. Senavirathna I, Rathish D, Agampodi S. Cytokine response in human leptospirosis with different clinical outcomes: a systematic review. BMC Infect Dis 2020; 20: 268.
28. Fernandes LGV, Vieira ML, Alves IJ, de Morais ZM, Vasconcellos SA, Romero EC, et al. Functional and immunological evaluation of two novel proteins of Leptospira spp. Microbiology (Reading) 2014; 160: 149-164.
29. Novak A, Hindriks E, Hoek A, Veraart C, Broens EM, Ludwig I, et al. Cellular and humoral immune responsiveness to inactivated Leptospira interrogans in dogs vaccinated with a tetravalent Leptospira vaccine. Vaccine 2023; 41: 119-129.
30. Marinho M, Silva C, Lima VMF, Peiró J, Rperri SHV. Citokine and antibody production during murine Leptospirosis. J Venom Anim Toxins Incl Trop Dis 2006; 12: 595-603.
31. Kita M. Role of IFN-gamma in nonviral infection. Nihon Rinsho 2006; 64: 1269-1274.
32. Vernel-Pauillac F, Goarant C. Differential cytokine gene expression according to outcome in a hamster model of Leptospirosis. PLoS Negl Trop Dis 2010; 4(1): e582.
33. Volz MS, Moos V, Allers K, Luge E, Mayer-Scholl A, Nockler K, et al. Specific CD4+ T-cell reactivity and cytokine release in different clinical presentations of Leptospirosis. Clin Vaccine Immunol 2015; 22: 1276-1284.
34. Umthong S, Buaklin A, Jacquet A, Sangjun N, Kerdkaew R, Patarakul K, et al. Immunogenicity of a DNA and recombinant protein vaccine combining LipL32 and Loa22 for Leptospirosis using chitosan as a delivery system. J Microbiol Biotechnol 2015; 25: 526-536.
35. Yan W, Faisal SM, McDonough SP, Chang CF, Pan MJ, Akey B, et al. Identification and characterization of OmpA-like proteins as novel vaccine candidates for leptospirosis. Vaccine 2010; 28: 2277-2283.
| Files | ||
| Issue | Vol 16 No 4 (2024) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijm.v16i4.16314 | |
| Keywords | ||
| Leptospirosis; Immunization; Enzyme-linked immunosorbent assay; Humoral immunity; Cellular immunity | ||
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How to Cite
1.
Golab N, Khaki P, Tebianian M, Esmaelizad M, Harzandi N. Recombinant outer membrane protein Lipl41 from Leptospira interrogans robust immune responses in mice model. Iran J Microbiol. 2024;16(4):545-551.
