J Pharm Pharmacogn Res 2(Suppl. 1): S9, 2014
Special supplement with the abstract book of LATINFARMA 2013
C 028: DEVELOPMENT OF EXPERIMENTAL STRATEGIES FOR THE PROPHYLAXIS AND TREATMENT OF TUBERCULOSIS
Acosta A1, Kadir R2, Ahmad F2, Puig A1, Borrero R1, Garcia MA1, Rodriguez L1, Camacho F1, Reyes F1, Aguilar A1, Otero O1, Rubio P1, Marron R1, Tirado Y1, Reyes F1, Alvarez N1, Infante JF1, Fernandez S1, Zayas C1, Lanio ME3, Acevedo R1, Mohd Nor N2, Perez Quiñoy JL1, Sarmiento ME.1
Tuberculosis remains as one of the main causes of morbidity and mortality due to infectious diseases. The current situation of the disease is characterized by an elevated morbidity and mortality, the low sensitivity of the diagnostic methods, the relative low therapeutic coverage, the growing appearance of multidrug resistant strains and the low efficacy of BCG in the prevention of adult pulmonary tuberculosis and the transmission of the disease. Taking into consideration these antecedents, the development of new prophylactic, diagnostic and therapeutic strategies are of the maximal priority internationally. Here we present our results in two main areas: The study of role of specific antibodies in the protection against mycobacteria, where different formulations of antibodies were evaluated in models of tuberculosis in mice. The administration of monoclonal IgA antibodies against Hspx antigen of M. tuberculosis by the mucosal route demonstrated a protective effect. M. tuberculosis preincubated with the same antibody decreased its infective capacity. In order to explore the potential for protection of human antibodies in the same model, human IgG formulations administered by the intranasal route protects mice from infection. The same effect was obtained when M. tuberculosis was administered to mice after preincubation with the human antibody formulation. Secretory human IgA purified from colostrums showed similar behavior than the previous formulations when evaluated in the same animal model. In another strategy, using the phage display technology, ligands specific for M. tuberculosis infected cells where developed. The results obtained with the different antibody formulations demonstrated the protective capacity of the specific antibody response against M. tuberculosis and support the application of these findings to the development of new vaccines and therapeutic tools against tuberculosis. Another area of interest is the evaluation of proteoliposomes and liposomes obtained from non pathogenic mycobacteria which where immunogenic and protective in mice.