A POTENTIAL MUCOSAL VACCINE AGANIST TUBERCULOSIS

MORELLI, MARIA PAULA; ZUAZO ROCIO; CANDELA MARTIN; MARIA PAULA DEL MEDICO ZAJAC; GABRIELA CALAMANTE; KARINA PASQUEVICH; LORENA CORIA; JULIANA CASSATARO; GARCIA VERONICA

San Luis

Congreso; LXXI REUNIÓN CIENTÍFICA ANUAL DE LA SOCIEDAD ARGENTINA DE INMUNOLOGÍA (SAI); 2023

BACKGROUND: Mycobacterium bovis BCG is not effective against pulmonary tuberculosis (TB), the most common form of TB in adults and teenagers. Thus, new vaccines conferring protection during the whole life of the individual are required. With the purpose to achieve multistage resistance against M. tuberculosis (Mtb) infection, we investigated the response of the host to two Mtb antigens: the 85A antigen (Ag85A), the protein most expressed in the initial stages of TB infection, and the Rv2626c antigen, a protein expressed under hypoxic conditions. To do this, we analysed the potential of both recombinant proteins or Modified Ankara Virus (MVA) vectors to be used as mucosal vaccines.METHODS: Balb/c mice were initially immunized by the sublingual (sl) or intranasal routes with Rv2626c and Ag85A proteins together with the Omp19 adjuvant (3 doses every 7 days). After 4 weeks, the animals were challenged with the pathogenic H37Rv Mtb strain by intratracheal inoculation. Thirty days post infection, lungs were aseptically removed and Mtb CFU counting was performed. Besides, we also assayed other immunization schedule by using two doses of MVA2626c Omp19 delivered by sl or intramuscular routes. Ten days after the last immunization, splenocytes were obtained and stimulated with recombinant Rv2626c, CD4+T cell-specific Rv2626c peptides, or CD8+T cell-specific MVA peptides. IFNγ production was measured by ELISA or Flow cytometry. Moreover, a group of experimental mice was challenged with H37Rv Mtb strain and afterward, CFUs were determined in lungs.RESULTS: By determining the CFUs in mice lungs, we observed that the intranasal Rv2626c+Ag85A+Omp19 vaccine preparation induced higher protection as compared to the same vaccine administered sublingually (p