Polymeric Approach to Adjuvant System in Antibody Production against Leishmaniasis Based on Hybridoma Technology
-
Asli Pinar Zorba Yildiz
,
Gulnaz Yildirim Koken
,
Emrah Sefik Abamor
,
Melahat Bagirova
,
Ozlem Ayse Tosyali
,
Tanil Kocagoz
,
Adil Allahverdiyev
Abstract
Background: Leishmaniasis is a zoonotic disease, which is one of the serious public health problems in the world. Nowadays, antibody production using hybridoma technology may be a correct approach in terms of sensitivity in the diagnosis of diseases such as leishmaniasis. The aim of this study was investigation of the effectiveness of different adjuvants on polyclonal antibody production against L. tropica based on hybridoma technique.
Methods: Accordingly, Freund's adjuvant (1956, M. tuberculosis), as a classic adjuvant in studies, was used comparatively with the non-toxic polymeric based Polyoxidonium adjuvant. All animal immunization procedures were conducted at Bezm-i Alem University Experimental Animal Research Center. The adjuvant response was tested both in the serum sample and in the antibodies produced by the hybridomas. The antibody titers were determined with ELISA.
Results: Freund’s and Polyoxidonium (PO) group blood titer’s increased approximately 5.5 fold compared to control after the 6th and 8th immunization. Hybridomas produced from mice immunized with PO adjuvant induced only antigen-specific antibody response and did not develop an immune response against the adjuvant.
Conclusion: Adjuvant selection is very important in terms of the specificity of antibody responses of cells produced in hybridoma technology. Therefore, PO is recommended as a new adjuvant system in this study.
1. Roque AL, Jansen AM. Wild and synan-thropic reservoirs of Leishmania species in the Americas. Int J Parasitol Parasites Wildl. 2014; 3:251-262.
2. Ertug S, Gultekin B, Doyuran ES. 2001 Yılında Aydın İl Sağlık Müdürlüğü'ne İhbar Edilen İç Organ ve Deri Leishmaniasis Olguları. ADÜ Tıp Fakultesi Dergisi. 2002; 3:9–12.
3. Handemir E, Oncel T, Kamburgil K. Is-tanbul Sokak Kopeklerinde Visseral Leishmaniasis Seroprevalansı. Turkiye Parazitol Derg. 2004; 28:123-125.
4. Organization WH. Expert Committee on the Control of Leishmaniases. In: Tech-nical Report Series 2010; 949.
5. Serin SM, Dağlıoğlu K, Bağırova M, et al. Rapid diagnosis and genotyping of Leish-mania isolates from cutaneous and visceral Leishmaniasis by microcapillary cultivation and polymerase chain reaction-restriction fragment length polymorphism of mini exon region. Diagn Microbiol Infect Dis. 2005; 53:209-214.
6. Ozbilgin A, Harman M, Karakus M, et al. Leishmaniasis in Turkey: Visceral and cu-taneous leishmaniasis caused by Leishmania donovani in Turkey. Acta Trop. 2017; 173: 90-96.
7. Allahverdiyev AM, Uzun S, Bağırova M, Durdu M, Memişoğlu HR. A sensitive new microculture method for diagnosis of cu-taneous leishmaniasis. Am J Tro Med Hyg. 2004; 70: 294-297.
8. Harith AE, Kolk AH J, Kager PA, et al. Evaluation of a newly developed direct ag-glutination test (DAT) for serodiagnosis and sero-epidemiological studies of viscer-al leishmaniasis: comparison with IFAT and ELISA. Trans R Soc Trop Med Hyg. 1987; 81(4), 603-606.
9. Ashford DA, Badaro R, Eulalio C, et al. Studies on the control of visceral leish-maniasis: validation of the Falcon assay screening test-enzyme-linked immuno-sorbent assay (FAST-ELISA™) for field diagnosis of canine visceral leishmaniasis. Am J Trop Med Hyg. 1993; 48(1):1-8.
10. Ozensoy S, Ozbel Y, Turgay N, et al. Se-rodiagnosis and epidemiology of visceral leishmaniasis in Turkey. Am J Trop Med Hyg. 1998; 59(3): 363-369.
11. El Safi SH, Evans DA. A comparison of the direct agglutination test and enzyme-linked immunosorbent assay in the sero-diagnosis of Leishmaniasis in the Sudan. Trans R Soc Trop Med Hyg. 1989; 83: 334-337.
12. Miller J. “The thymus in immunity”. Princ Med Biol. 1996; 6: 1-20.
13. Mathur P, Samantaray JC. The first proba-ble case of platelet transfusion-transmitted visceral leishmaniasis. Transfus Med. 2004; 14(4), 319–321.
14. Khabiri AR, Bagheri F, Naddaf SR, Ass-mar M, Taghavi AH. Characterization of a Monoclonal Antibody Specific for the Par-asite Surface Antigen-2 of Leishmania major. Iran J Public Health. 2004; 10-14.
15. Fong D, Chang KP. Surface antigenic change during differentiation of a parasitic protozoan, Leishmania mexicana: Identifica-tion by monoclonal antibodies. Proc Natl Acad Sci U S A. 1982; 79(23): 7366-7370.
16. Handman E, Hocking RE. Stage-specific, strain-specific, and cross-reactive antigens of Leishmania species identified by mono-clonal antibodies. Infect Immun. 1982; 37(1), 28-33.
17. Nejad-Moghaddam A, Abolhassani M. Epitope mapping of a common 57 kDa antigen of Leishmania species by monoclo-nal antibodies. Vaccine. 2010; 28(37), 6036-6040.
18. Nejad-Moghaddam A, Abolhassani M. Production and characterization of mono-clonal antibodies recognizing a common 57-kDa antigen of Leishmania species. Iran Biomed J. 2009; 13(4): 245-251.
19. Aguilar JC, Rodriguez EG. Vaccine adju-vants revisited. Vaccine. 2007; 25: 3752-3762.
20. Nouri A, Mohamed FAN, Laraba-Djebari F. New and safe formulation for scorpion immunotherapy: Comparative study be-tween saponin and FCA adjuvants associ-ated to attenuated venom. Vaccine. 2018; 36(13): 1720-1727.
21. Oscherwitz J, Hankenson FC, Yu F, Cease KB. Low-dose intraperitoneal Freund's ad-juvant: Toxicity and immunogenicity in mice using an immunogen targeting amy-loid-β peptide. Vaccine. 2006; 24(15): 3018-3025.
22. Dyakonova VA, Dambaeva SV, Pinegin BV, Khaitov RM. Study of interaction be-tween the polyoxidonium immunomodu-lator and the human immune system cells. Int. Immunopharmacol. 2004; 4(13):1615-1623.
23. Toptygina A, Semikina E, Alioshkin V. Influence of an immunopotentiator poly-oxidonium on cytokine profile and anti-body production in children vaccinated with Priorix. Arch Physiol Biochem. 2012; 118(4): 197-203.
24. Aydogdu M, Bagirova M, Allahverdiyev A, et al. Large-scale cultivation of Leishmania infantum promastigotes in stirred bioreac-tor. J Vector Borne Dis. 2019;56(4):345-350.
25. Tosyali OA, Allahverdiyev A, Bagirova M, et al. Nano-co-delivery of lipophosphogly-can with soluble and autoclaved Leishmania antigens into PLGA nanoparticles: Evalua-tion of in vitro and in vivo immunostimu-latory effects against visceral leishmaniasis. Mater Sci Eng C Mater Biol Appl. 2021; 120:111684.
26. Ethan A, Lerner BA. How to Make a Hy-bridoma. Yale J Biol Med. 1981; 54: 387-402.
27. Sereda AD, Makarov VV, Sachivkina NP, et al. Effectiveness of combined use: inac-tivated vaccines with immunostimulants on the in vivo model of teschen disease. Adv Anim Vet Sci. 2020; ISSN (Online) 2307-8316; ISSN (Print) 2309-3331.
28. Nourizadeh E, Zargar SJ, Alimohammadi-an MH, Ajdary S, Mahdavi M. Develop-ment of monoclonal antibodies against axenic amastigotes of Leishmania infantum strain in Iran: implication for diagnosis of Kala-azar. Iran J Basic Med Sci. 2018; 21(4):388.
29. El Roufaie Mohammed EA, Wright E, Kager PA, Laarman J, Pondman K. ELI-SA using intact promastigotes for immu-nodiagnosis of kala-azar. Trans R Soc Trop Med Hyg. 1985; 79: 344-350.
30. Allahverdiyev AM, Koc RC, Bagirova M, et al. A new approach for development of vaccine against visceral leishmaniasis: Lip-ophosphoglycan and polyacrylic acid con-jugates. Asian Pac J Trop Med. 2017; 10(9):877-886.
31. Topuzogullari M, Cakir Koc R, Dincer Isoglu S, et al. Conjugation, characteriza-tion and toxicity of lipophosphoglycan-polyacrylic acid conjugate for vaccination against leishmaniasis. J Biomed Sci. 2013; 3;20(1):35
32. Herwaldt BL. Leishmaniasis. Lancet. 1999; 354:1191-1199.
33. Rezaei Z, Van Reet N, Pouladfar G, et al. Expression of a rK39 homologue from an Iranian Leishmania infantum isolate in Leish-mania tarentolae for serodiagnosis of visceral leishmaniasis. Parasit Vectors. 2019; 18;12(1):593.
34. Sanchez MCA, Celeste BJ, Lindoso JAL, et al. Performance of rK39-based immu-nochromatographic rapid diagnostic test for serodiagnosis of visceral leishmaniasis using whole blood, serum and oral fluid. PLoS One. 2020; 15(4):e0230610.
35. Paul WE. The Immune System: An Intro-duction, Fundamental Immunology. 7th Ed 2013.
36. Delves PJ, Martin SJ, Burton DR, Roitt IM. Roitt's essential immunology. Wiley-Blackwell. 2011.
37. Janeway CA, Travers P, Walport M, Shlomchik M. Immunobiology: The Im-mune System in Health & Disease. 2005.
38. Freund J. The mode of action of immuno-logical adjuvants. Adv Tuberc Res. 1956; 7:130–148.
39. Basu P, Saha N, Saha T, Saha P. Polymeric hydrogel based systems for vaccine deliv-ery: A review. Polymer. 2021; Volume 230, 124088.
40. W. Jianga, R.K. Gupta, M.C. Deshpande, S.P. Schwendeman. Biodegradable poly (lactic-co-glycolic acid) microparticles for injectable delivery of vaccine antigens. Adv Drug Deliv Rev. 57. 2005; 391–410.
2. Ertug S, Gultekin B, Doyuran ES. 2001 Yılında Aydın İl Sağlık Müdürlüğü'ne İhbar Edilen İç Organ ve Deri Leishmaniasis Olguları. ADÜ Tıp Fakultesi Dergisi. 2002; 3:9–12.
3. Handemir E, Oncel T, Kamburgil K. Is-tanbul Sokak Kopeklerinde Visseral Leishmaniasis Seroprevalansı. Turkiye Parazitol Derg. 2004; 28:123-125.
4. Organization WH. Expert Committee on the Control of Leishmaniases. In: Tech-nical Report Series 2010; 949.
5. Serin SM, Dağlıoğlu K, Bağırova M, et al. Rapid diagnosis and genotyping of Leish-mania isolates from cutaneous and visceral Leishmaniasis by microcapillary cultivation and polymerase chain reaction-restriction fragment length polymorphism of mini exon region. Diagn Microbiol Infect Dis. 2005; 53:209-214.
6. Ozbilgin A, Harman M, Karakus M, et al. Leishmaniasis in Turkey: Visceral and cu-taneous leishmaniasis caused by Leishmania donovani in Turkey. Acta Trop. 2017; 173: 90-96.
7. Allahverdiyev AM, Uzun S, Bağırova M, Durdu M, Memişoğlu HR. A sensitive new microculture method for diagnosis of cu-taneous leishmaniasis. Am J Tro Med Hyg. 2004; 70: 294-297.
8. Harith AE, Kolk AH J, Kager PA, et al. Evaluation of a newly developed direct ag-glutination test (DAT) for serodiagnosis and sero-epidemiological studies of viscer-al leishmaniasis: comparison with IFAT and ELISA. Trans R Soc Trop Med Hyg. 1987; 81(4), 603-606.
9. Ashford DA, Badaro R, Eulalio C, et al. Studies on the control of visceral leish-maniasis: validation of the Falcon assay screening test-enzyme-linked immuno-sorbent assay (FAST-ELISA™) for field diagnosis of canine visceral leishmaniasis. Am J Trop Med Hyg. 1993; 48(1):1-8.
10. Ozensoy S, Ozbel Y, Turgay N, et al. Se-rodiagnosis and epidemiology of visceral leishmaniasis in Turkey. Am J Trop Med Hyg. 1998; 59(3): 363-369.
11. El Safi SH, Evans DA. A comparison of the direct agglutination test and enzyme-linked immunosorbent assay in the sero-diagnosis of Leishmaniasis in the Sudan. Trans R Soc Trop Med Hyg. 1989; 83: 334-337.
12. Miller J. “The thymus in immunity”. Princ Med Biol. 1996; 6: 1-20.
13. Mathur P, Samantaray JC. The first proba-ble case of platelet transfusion-transmitted visceral leishmaniasis. Transfus Med. 2004; 14(4), 319–321.
14. Khabiri AR, Bagheri F, Naddaf SR, Ass-mar M, Taghavi AH. Characterization of a Monoclonal Antibody Specific for the Par-asite Surface Antigen-2 of Leishmania major. Iran J Public Health. 2004; 10-14.
15. Fong D, Chang KP. Surface antigenic change during differentiation of a parasitic protozoan, Leishmania mexicana: Identifica-tion by monoclonal antibodies. Proc Natl Acad Sci U S A. 1982; 79(23): 7366-7370.
16. Handman E, Hocking RE. Stage-specific, strain-specific, and cross-reactive antigens of Leishmania species identified by mono-clonal antibodies. Infect Immun. 1982; 37(1), 28-33.
17. Nejad-Moghaddam A, Abolhassani M. Epitope mapping of a common 57 kDa antigen of Leishmania species by monoclo-nal antibodies. Vaccine. 2010; 28(37), 6036-6040.
18. Nejad-Moghaddam A, Abolhassani M. Production and characterization of mono-clonal antibodies recognizing a common 57-kDa antigen of Leishmania species. Iran Biomed J. 2009; 13(4): 245-251.
19. Aguilar JC, Rodriguez EG. Vaccine adju-vants revisited. Vaccine. 2007; 25: 3752-3762.
20. Nouri A, Mohamed FAN, Laraba-Djebari F. New and safe formulation for scorpion immunotherapy: Comparative study be-tween saponin and FCA adjuvants associ-ated to attenuated venom. Vaccine. 2018; 36(13): 1720-1727.
21. Oscherwitz J, Hankenson FC, Yu F, Cease KB. Low-dose intraperitoneal Freund's ad-juvant: Toxicity and immunogenicity in mice using an immunogen targeting amy-loid-β peptide. Vaccine. 2006; 24(15): 3018-3025.
22. Dyakonova VA, Dambaeva SV, Pinegin BV, Khaitov RM. Study of interaction be-tween the polyoxidonium immunomodu-lator and the human immune system cells. Int. Immunopharmacol. 2004; 4(13):1615-1623.
23. Toptygina A, Semikina E, Alioshkin V. Influence of an immunopotentiator poly-oxidonium on cytokine profile and anti-body production in children vaccinated with Priorix. Arch Physiol Biochem. 2012; 118(4): 197-203.
24. Aydogdu M, Bagirova M, Allahverdiyev A, et al. Large-scale cultivation of Leishmania infantum promastigotes in stirred bioreac-tor. J Vector Borne Dis. 2019;56(4):345-350.
25. Tosyali OA, Allahverdiyev A, Bagirova M, et al. Nano-co-delivery of lipophosphogly-can with soluble and autoclaved Leishmania antigens into PLGA nanoparticles: Evalua-tion of in vitro and in vivo immunostimu-latory effects against visceral leishmaniasis. Mater Sci Eng C Mater Biol Appl. 2021; 120:111684.
26. Ethan A, Lerner BA. How to Make a Hy-bridoma. Yale J Biol Med. 1981; 54: 387-402.
27. Sereda AD, Makarov VV, Sachivkina NP, et al. Effectiveness of combined use: inac-tivated vaccines with immunostimulants on the in vivo model of teschen disease. Adv Anim Vet Sci. 2020; ISSN (Online) 2307-8316; ISSN (Print) 2309-3331.
28. Nourizadeh E, Zargar SJ, Alimohammadi-an MH, Ajdary S, Mahdavi M. Develop-ment of monoclonal antibodies against axenic amastigotes of Leishmania infantum strain in Iran: implication for diagnosis of Kala-azar. Iran J Basic Med Sci. 2018; 21(4):388.
29. El Roufaie Mohammed EA, Wright E, Kager PA, Laarman J, Pondman K. ELI-SA using intact promastigotes for immu-nodiagnosis of kala-azar. Trans R Soc Trop Med Hyg. 1985; 79: 344-350.
30. Allahverdiyev AM, Koc RC, Bagirova M, et al. A new approach for development of vaccine against visceral leishmaniasis: Lip-ophosphoglycan and polyacrylic acid con-jugates. Asian Pac J Trop Med. 2017; 10(9):877-886.
31. Topuzogullari M, Cakir Koc R, Dincer Isoglu S, et al. Conjugation, characteriza-tion and toxicity of lipophosphoglycan-polyacrylic acid conjugate for vaccination against leishmaniasis. J Biomed Sci. 2013; 3;20(1):35
32. Herwaldt BL. Leishmaniasis. Lancet. 1999; 354:1191-1199.
33. Rezaei Z, Van Reet N, Pouladfar G, et al. Expression of a rK39 homologue from an Iranian Leishmania infantum isolate in Leish-mania tarentolae for serodiagnosis of visceral leishmaniasis. Parasit Vectors. 2019; 18;12(1):593.
34. Sanchez MCA, Celeste BJ, Lindoso JAL, et al. Performance of rK39-based immu-nochromatographic rapid diagnostic test for serodiagnosis of visceral leishmaniasis using whole blood, serum and oral fluid. PLoS One. 2020; 15(4):e0230610.
35. Paul WE. The Immune System: An Intro-duction, Fundamental Immunology. 7th Ed 2013.
36. Delves PJ, Martin SJ, Burton DR, Roitt IM. Roitt's essential immunology. Wiley-Blackwell. 2011.
37. Janeway CA, Travers P, Walport M, Shlomchik M. Immunobiology: The Im-mune System in Health & Disease. 2005.
38. Freund J. The mode of action of immuno-logical adjuvants. Adv Tuberc Res. 1956; 7:130–148.
39. Basu P, Saha N, Saha T, Saha P. Polymeric hydrogel based systems for vaccine deliv-ery: A review. Polymer. 2021; Volume 230, 124088.
40. W. Jianga, R.K. Gupta, M.C. Deshpande, S.P. Schwendeman. Biodegradable poly (lactic-co-glycolic acid) microparticles for injectable delivery of vaccine antigens. Adv Drug Deliv Rev. 57. 2005; 391–410.
| Files | ||
| Issue | Vol 17 No 4 (2022) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijpa.v17i4.11278 | |
| Keywords | ||
| Leishmaniasis Antibody Hybridoma technology Adjuvant Vaccine | ||
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How to Cite
1.
Zorba Yildiz A, Yildirim Koken G, Abamor E, Bagirova M, Tosyali O, Kocagoz T, Allahverdiyev A. Polymeric Approach to Adjuvant System in Antibody Production against Leishmaniasis Based on Hybridoma Technology. Iran J Parasitol. 2022;17(4):506-516.
