Original article. Inmunoprotector potential of cellular vaccine formulations developed from Leptospira interrogans Ballum using Mesocricetus auratus as biomodel

Open access

Abstract

Background: In the last years, Leptospira spp Ballum has increased its representation in human clinical isolations in Cuba. Effective vaccines are needed to control this zoonotic disease.

Objective: With the objective of developing a new vaccine candidate able to generate an effective protection against this serovar, two monovalent formulations developed by two highly virulent strains were evaluated (FoBa and FoBb).

Methods: Clinical isolates of Leptospira serovar Ballum were subjected to serial passages in hamsters and monovalent vaccines were produced by modified methods developed for vax-SPIRAL®. The vaccine efficacy was tested in both experimental and control hamsters.

Results: The Mesocricetus auratus biomodel showed that both formulations generated a protection of 100% against the Ballum lethal infection together to high levels of IgG antibodies and were efficient in the elimination of homologous carrier state but not heterologous carrier states.

Conclusion: Both FoBa and FoBb vaccines were protective against leptospirosis with high IgG titers, absence of clinical signs and dead, and absence of leptospires in kidney of sacrificed animals.

1. Panamerican Health Organization. Poors desease [Internet]. 2009 [cited 2009 Mar 4]. Available from: http://www.paho.org/Spanish/AD/DPC/CD/psit-ndposter.htm

2. Brenner D, Kaufmann A, Sulzer K, Steigerwalt A, Rogers F, Weyant R. Further determination of DNA relatedness between serogroups and serovars in the family Leptospiraceae with a proposal for Leptospira alexanderi sp. and four new Leptospira genomospecies. Int J Syst Bacteriol. 1999; 49:839-58.

3. Adler B, de la Peña M. Leptospira and Leptospirosis. Vet Microbiol. 2009; 2:4382-92.

4. Levett P. Leptospirosis. Clin Microbiol Rev. 2001; 14: 296-326.

5. Cinco M, Domenis R, Perticarari S, Presani G, Marangoni A, Blasi E. Interaction of leptospires with murine microglial cells. New Microbiol. 2006; 29:193-9.

6. McBride A, Athanazio D, Reis M, Ko A. Leptospirosis. Curr Opin Infect Dis. 2005; 18:376-86.

7. WHO/FAO/OIE Collaborating Centre for Reference and Research on Leptospirosis. National Leptospirosis Surveillance Report number 17 [Internet]. 2009 [cited 2009 Mar 4]. Available from: http://www.health.qld.gov.au/qhcss/documents/lepto/08_annual.pdf;2009

8. World Health Organization. WHO Guidelines on Non-clinical Evaluation of Vaccines. 2003.

9. Faine S. Leptospira and Leptospirosis. Clayton, Victoria, Australia: CRC Press. 1994.

10. Haake D, Chao G, Zuerner R, Barnett J, Barnett D, Mazel M. The leptospiral major outer membrane protein LipL32 is a lipoprotein expressed during mammalian infection. Infect Immun. 2000; 68:2276-85.

11. Andre-Fontaine G, Branger C, Gray A, Klaasen H. Comparison of the efûcacy of three commercial bacterins in preventing canine leptospirosis. Vet Rec. 2003; 153:165-9.

12. Wan Z, Jin L, Wegrzyn A. Leptospirosis vaccines. Microb Cell Fac. 2007; 6:1-10.

13. Martínez R, Pérez A, Baró M, Alvarez M, Menéndez J, Díaz M. Evaluation of the effectiveness of a new vaccine against human leptospirosis in groups at risk. Rev Panam Sal Pub. 2000; 8:385-92.

14. Rodríguez I, Fernández C, Obregon A, Zamora Y, Rodríguez J, Rodríguez N. Epidemological behavior of the leptospirosis in Cuba 2006-2008, Leptospirosis Havana 2009. Proceedings of I SAW Scientific Meeting, 2009 Jun 8-12; Havana, Cuba.

15. Haake D. Hamster model of leptospirosis. Curr Protoc Microb. 2006 Sep;Chapter 12:Unit 12E.2.

16. Silva E, Santos S, Athanazio D, Seyffert N, Seixas F, Cerqueira G. Characterization of virulence of Leptospira isolates in a hamster model. Vaccine. 2008; 26:3892-6.

17. González M, Martínez R, Cruz R, Infante J, González I. vax-SPIRALR. Trivalent antileptospirosic vaccine for human use, investigation, development and impact on the illness in Cuba. Biotec. Aplic. 2004; 2:107-11.

18. American Veterinary Medical Association. Guidelines on Euthanasia. Fromerly report of the AVMA panel on Euthanasia; 2007.

19. Silva E, Medieros M, Mc Bride A, Matasunga J, Esteves G, Ramos J. The terminal portion of leptospiral immunoglobulin-like protein Lig A confers protective immunity against lethal infection in the hamster model of leptospirosis. Vaccine. 2007; 25:6277-86.

20. Reed J, Muench H. simple method of estimation ûfty percent end-points. American Journal of Hygiene. 1938; 27:493-7.

21. Finlay Institute. Sanitary Registration of vax- SPIRAL (trivalent antileptospirosic vaccine); 1998. p.23-25.

22. Freudenstein H, Hein B. Potency of Leptospiral vaccines and protection against chronic infection in golden hamsters. Comp Immunol Microb Infect Dis. 1991; 14:229-34.

23. Tepstra W, Hartskeerl R, Smits H, Korver H. International Course in Laboratory Techniques for the Diagnosis of Leptospirosis. KIT Biomedical Research. International. Royal Tropical Institute, Amsterdam, 2006, 1-124.

24. Hem A, Smith A, Solberg P. Saphenous vein puncture for blood sampling of the mouse, rat, hamster, gerbil, guinea pig, ferret, and mink. Lab Anim. 1998; 32:364-8.

25. Silva M, Camargo E, Batista L, Vaz A, Brandao A, Nakamura P. Behaviour of specific IgM, IgG and IgA class antibodies in human leptospirosis during the acute phase of the disease and during convalescence. J Trop Med Hyg. 1995; 98:268-72.

26. Nu ez J, Fajardo E, Perez E, Ontivero I, Silva D, Munoz P. Evaluation of two different potency tests for leptospirosis vaccine vax-spiral. Rev Cub Med Tropic. 2005; 57:67-8.

27. Falkow S. Molecular Koch’s postulates applied to microbial pathogenicity. Rev Infect Dis. 1988; 10: 274-6.

28. Shenberg E, Torten M. A new leptospiral vaccine for use in man. I. Development of a vaccine from Leptospira grown in a chemicacally defined medium. J Inf Dis.1973; 128:642-6.

29. Levett P, Morey R, Gallowway R, Turner D, Steigerwalt A, Mayer L. Detection of pathogenic leptospires by real-time quantitative real-time PCR. J Med Microbiol. 2005; 54:45-9.

30. Matsunaga J, Barocchi M, Croda J, Young T, Sanchez Y, Siqueira I. Pathogenic Leptospira species express surface-exposed proteins belonging to the bacterial immunoglobulin superfamily. Molecul Microbiol. 2003; 49:929-46.

31. Choy H, Kelley M, Chen T, Moller A, Matsunaga J, Haake D. Physiological osmotic induction of Leptospira interrogans adhesion: LigA and LigB bind extracellular matrix proteins and fibrinogen. Infect Immun. 2007; 75:2441-50.

32. Gonzalez A, Rodriguez Y, Batista N, Valdes Y, Nu ez J, Gonzalez M. Booster effect of an active immunization with Leptospira interrogans serogroup Ballum in hamsters vaccinated with vax-SPIRAL. Vacci Monitor. 2003; 12:1-6.

33. Faine S, Adler B, Bolin C, Perolat P: Leptospira and Leptospirosis. 2nd edition. Melbourne, Australia: MediSci; 1999.

34. Sonrier C, Branger C, Michel V, Ruvoen N, Ganiere J, Andre G. Evidence of cross-protection within Leptospira interrogans in an experimental model. Vaccine. 2000; 19:86-94.

35. Coutinho ML, Choy HA, Kelley MM, Matsunaga J, Babbitt JT, Lewis M, Aleixo JA, Haake D. A LigA Three- Domain Region Protects Hamsters from Lethal Infection by Leptospira interrogans. PLoS Negl Trop Dis. 2011; 5:e1422.

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