ABSTRACT
Objective/background: The search for new vaccines more efficacious than bacille Calmette-Guerin for tuberculosis prevention is of paramount importance for the control of the disease. The expression of Mycobacterium tuberculosis antigens in Mycobacterium smegmatis is one of the current strategies for the development of new-generation vaccines against tuberculosis. The objective of this study was to evaluate the immunogenicity in mice of M. smegmatis expressing epitopes from Ag85B antigen
Methods: M. smegmatis expressing three T cell epitopes from M. tuberculosis Ag85B [P21, P26, and P53] was constructed [rMs064]. rMs064 was used to immunize BALB/C mice for immunogenicity evaluation. The present study investigates the capacity of rMs064 to induce specific cellular and humoral immune responses against the expressed epitopes. Cytokine production upon stimulation with Ag85B peptides and specific total immunoglobulin G and immunoglobulin G subclasses were determined
Results: The results showed a significant production of interleukin-12 and interleukin-23 when splenocytes were stimulated with P21, P26, and P53 peptides, and interferon-gamma after stimulation with P21 in animals immunized with rMs064 compared with controls. The total immunoglobulin G and its subclasses showed significant increases against the Ag85B epitapes in the sera of rMs064-immunized mice compared with the control groups
Conclusion: The results of this study support the future evaluation of rMs064 as a vaccine candidate against tuberculosis in challenge experiments
Subject(s)
Animals, Laboratory , Immunity, Humoral , Immunity, Cellular , Epitopes , Recombinant Fusion Proteins , Tuberculosis Vaccines , Tuberculosis , Antigens, Bacterial , MiceABSTRACT
Research, development, and production of vaccines are still highly dependent on the use of animal models in the various evaluation steps. Despite this fact, there are strong interests and ongoing efforts to reduce the use of animals in vaccine development. Tuberculosis vaccine development is one important example of the complexities involved in the use of animal models for the production of new vaccines. This review summarises some of the general aspects related with the use of animals in vaccine research and production, as well as achievements and challenges towards the rational use of animals, particularly in the case of tuberculosis vaccine development.
ABSTRACT
Uno de los problemas de la seguridad para las vacunas de ADN es la inducción de fenómenos de autoinmunidad. Nosotros examinamos el efecto de la inmunización con ácidos nucleicos de Trypanosoma cruzi en la inducción de diferentes autoanticuerpos en ratones de Balb/c. Los animales fueron divididos en cinco grupos: los primeros cuatro recibieron diferentes esquemas: 25 µg de la biblioteca genómica de expresión (grupo L), 25 µg de antígenos solubles de T. cruzi (grupo T), 25 µg del plásmido pcDNA3 (grupo P), 25 µg de genómica ADN de T. cruzi (grupo G) y un grupo control de animales no inmunizados. Los anticuerpos antinucleares y anticuerpos contra músculo cardíaco fueron evaluados por immunofluorescencia indirecta y los anticuerpos anti ADN de doble, simple cadena y el anti IgG factor reumatoideo fueron determinados semanalmente por ELISA. La vacunación no provocó la inducción de anticuerpos anti ADN de doble o simple cadena, anticuerpos antinucleares ni contra músculo cardíaco. Se observó un aumento transitorio del Factor Reumatoideo IgG en los ratones inmunizados con la biblioteca genómica de expresión de T. cruzi. Nuestros hallazgos sugieren que la inducción de respuestas autoinmunes frente al ADN utilizado en la inmunización es poco probable