Viejos y nuevos enfoques para el desarrollo de vacunas contra la tuberculosis.
Old and New approaches for Vaccines against tuberculosis.
H. Bercovier.
Department of Clinical Microbiology. The Hebrew University-Hadassah Medical School. Ein Karem, Jerusalem, 91120, Israel.
E-Mail:HB@cc.huji.ac.il ]]>
RESUMEN
¿Necesitamos esfuerzos renovados para desarrollar nuevas vacunas para combatir la tuberculosis? Los datos
epidemiológicos muestran que la disminución de la ya baja incidencia de tuberculosis se ha detenido en los países en desarrollo. En ciertos países occidentales la incidencia de tuberculosis ha aumentado incluso en los últimos 10 años. En Africa y Asia se encontró una alta incidencia de tuberculosis similar a la del mundo occidental en los años 30. ¿Podemos predecir por la historia de la tuberculosis en Europa Occidental que la epidemia de tuberculosis en los países en desarrollo ya alcanzó su pico o se encuentra todavía en aumento? Datos revisados muestran que en Europa la epidemia de tuberculosis comenzó al menos tres siglos antes de alcanzar su apogeo a mediados del siglo XIX. Las razones para la disminución de la tuberculosis en la primera mitad del siglo XX en el mundo occidental todavía no son bien comprendidas.¿Las medidas de salud pública o el adecuado tratamiento con antibióticos reducirán o detendrán la tuberculosis en Africa y Asia o continuará aumentando la tuberculosis? Nuestra posibilidad para controlar la diseminación de la enfermedad se complica por la aparición de cepas resistentes a antibióticos y el VIH. Por lo tanto se requiere una mejor comprensión de la base molecular de la interacción entre el bacilo y sus huéspedes para el desarrollo de mejores enfoques de tratamiento e inmunización. La inmunidad celular y la hipersensibilidad de tipo retardado (HTR) son procesos claves en el curso de la infección por el Mycobacterium y están involucradas tanto en la infección primaria como en la secundaria, así como en la inducción de la inmunidad protectora en el huésped. Los diferentes tipos de vacuna contra la tuberculosis que están siendo reevaluadas incluyen: BCG con dosis de refuerzo, BCG oral, BCG modificada (multivalente), cepas auxotróficas atenuadas del M. tuberculosis, proteínas secretadas o recombinantes de M. tuberculosis con o sin inmunomoduladores y vacunas de ADN. Estas nuevas vacunas inducen una buena inmunidad celular y pueden contribuir al desarrollo de enfoques mejorados
de inmunización y tratamiento.
Palabras claves: Vacunas, tuberculosis, Mycobacterium tuberculosis
ABSTRACT
Do we need renewed efforts to develop new vaccines to fight tuberculosis? Epidemiological data show that the decrease of the already low incidence of tuberculosis has stopped in developed countries. In certain Western countries the incidence of tuberculosis has even increased in the last ten years. In Africa and in Asia, a high incidence of tuberculosis is found similar to that of the Western world in the 1930s. Can we predict from the history of tuberculosis in Western Europe that the epidemic of tuberculosis in developing countries has reached his peak or is still developing? Revisited data from Europe show that the epidemic of tuberculosis started at least three centuries before it reached its apogee in the middle of the 19th century. The reasons for the decrease of tuberculosis in the first half of the 20th century in the Western world are still not well understood. Will public health measures and proper antibiotic treatment reduce and stop tuberculosis in Africa and in Asia or will the incidence of tuberculosis increase? Our ability to control the spread of the disease is complicated by the appearance of antibiotic resistant strains and HIV. Therefore, a better understanding of the molecular basis for the interaction between the bacilli and the hosts is necessary for the development of improved approaches for treatment and immunization. Cellular immunity and delayed type hypersensitivity (DTH) are key processes in the course of mycobacterial infection and are involved in both primary and secondary infection as well as in the induction of protective immunity in the host. The different types of tuberculosis vaccines being reevaluated comprise: BCG with booster, oral BCG, modified BCG (multivalent), auxotrophic M. tuberculosis attenuated strains, M. tuberculosis secreted proteins or recombinant proteins with or without immunomodulators and DNA vaccines. These new vaccines inducing a good cellular immunity may contribute to the development of improved approaches for immunization and treatment.
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REFERENCIAS
1. Andersen P, Heron I. Specificity of protective memory immune response against Mycobacterium tuberculosis. Infect Immun 1993; (61):844-851.
2. Bertolli J, Pangi C, Frerichs R, Halloran ME. A case-control study of the effectiveness of BCG vaccine for preventing leprosy in Yangon, Myanmar. Int J Epidemiol 1997; (26):888-896.
3. Chaussinaud R. Tuberculose et lepre. Maladies antagonistes. Eviction de la lepre par la tuberculose. Intern J Leprosy 1948; 16:430.
4. Corlan E. The incidence of tuberculosis in Romania in 1994. Pneumoftiziologia. 1995; 44:9-16.
5. Cosivi O, Grange JM, Daborn CJ, Raviglione MC, Fujikura T, Cousins D, Robinson RA, Huchzermeyer HFAK, de Kantor I, Meslin FX. Zoonotic tuberculosis due to Mycobacterium bovis in developing countries. Emerg Infect Dis 1998. 4: http://www.cdc.gov/ncidod/EID/vol4no1/cosivi.htm.
6. Daniel M., Bates JH., Downes KA. History of tuberculosis in Tuberculosis, Pathogenesis, Protection and Control. BR. Bloom, ed. Washington, DC: ASM; 1994.
7. Davis HL, Michel ML, Whalen RG. DNA-based immunization induces continuous secretion of hepatitis B surface antigen and high levels of circulating antibody. Human Mol. Genet. 1993; (2):1847-1851.
8. Dolin PJ, Raviglione, MC, Koch, A. Global tuberculosis incidence and mortality during 1990-2000. Bull. World Health Organ. 1994; (72): 213-220.
9. Dubos R. and Dubos J. Tuberculosis, Man, and Society: the White Plague. Boston: Little, Brown & Co.; 1952.
10. Faerman M, Jankauskas R., Gorski A., Bercovier H. Greenblatt CL. Prevalence of human tuberculosis in a medieval population of Lithuania studied by ancient DNA analysis. Ancient Biomolecules 1997; (1):205-214.
11. Fishman Y and Bercovier H. Involvement of L7/L12 in DTH reaction in mycobacterial infections J. Cell Biochem. 1995. Suppl. 19B:77 abstract B3-229.
12. Horwitz MA., Byong-Wha EL., Dillon BJ. and Harth G. Protective immunity against tuberculosis induced by vaccination with major extracellular vaccine of M. tuberculosis Proc. Natl. Acad Sci.,USA. 1994 (92):1530-1534.
13. Hsu-yu H. The epidemiologic status of lung tuberculosis in China 1979 and 1984/85. The result of the 2nd nationwide randomized prevalence study. Pneumologie. 1993; (4):450-455.
14. Karonga Prevention Trial Group. Randomised controlled trial of single BCG, repeated BCG or combined BCG and killed Mycobacterium leprae vaccine for prevention of leprosy and tuberculosis in Malawi. Lancet. 1996; (348):17-24.
15. Lombardi C., Pedrazzani E.S. Pedrazzani JC., Filho PF, Zicker F. Protective efficacy of BCG against leprosy in Sao Paulo. Bull Pan Am Health Organ 1996; (30):24-30.
16. Lowlell A. M. Tuberculosis: its social and economic impact and some thoughts on epidemiology. Microbiol Ser 1984; (15):1021-1055.
17. Lowrie DB., Silva CL., Colston MJ. Ragno S., Tascon RE. Protection against tuberculosis by a plasmid DNA vaccine.Vaccine 1997; 15:834-838.
18. Lozes E., Huygen K., Content J., Denis O., Montgomery D.L., Yawman AM., Vandenbussche P., Van Vooren JP., Drowart A., Ulmer J.F., Liu MA.. Immunogenicity and efficacy of tuberculosis DNA vaccine encoding the components of the secreted antigen 85 complex. Vaccine 1997; 15:830-833.
19. Matsuoka M., Nomaguchi H., Yukitake H., Ohara N., Matsumoto S., Mike S., Yamada T. Inhibition of multipli-cation of Mycobacterium leprae in mouse foot pads by im-munization with ribosomal fraction and culture filtrate from Mycobacterium bovis BCG. Vaccine. 1997;15:1214-1217.
20. Orme IM., Miller E.S., Roberts AD., Furney SK., Griffin JP., Dobos .M., Chi D., Rivoire B., Brennan PJ.. T lymphocytes mediating protection and cellular cytolysis during the course of Mycobacterium tuberculosis infection. Evidence for different kinetics and recognition of a wide spectrum of protein antigens. J. Immunol. 1992; (148): 189-196.
21. Raviglione MC., Snider DE Jr. and A. Kochi, Global epidemiology of tuberculosis. Morbidity and Mortality of worldwide epidemic. JAMA. 1995; (273):220-226.
22. Smith D.W. BCG. Microbiol. Ser. 1984; (15):1057-1070.
23. Sudre P., ten-Dam G., Kochi A. Tuberculosis: a global overview of the situation today. Bull. World Health Organ. 1992; (70):149-159.
24. Ulmer JB., Donnely JJ.,. Parker SE, Rhodes GH., Felgner PL., Dwarki VJ., Gromkowski S.H, Deck RR., Leander C.M., Martinez D., Perry HC., Shiver JW, Mongomery DL. and Liu M.A. Heterologous protection against influenza by injection of DNA encoding a viral protein. Science. 1993; (259):1745-1749.
25. Wang B., Ugen KE., Srikantan V., Agadjanyan MG, Dang K., Refaeli Y., Sato AI, Boyer J., Williams WV, and Weiner DB. Gene inoculation generates immune responses against human immunoideficiency virus type 1. Proc. Natl. Acad. Sci. USA. 1993; (90):4156-4160. ]]>