Immune Response to the Recombinant Apa Protein from Mycobacterium tuberculosis Expressed in Streptomyces lividans After Intranasal Administration in Mice. Induction of Protective Response to Tubercle Bacillus Aerosols Exposure
Por:
Martínez-Sotelo, JA, Vallecillo, AJ, Parada, C, Segura, E, Campuzano, J, Silva-Miranda, M, Servín-González, L, Espitia, C
Publicada:
1 jul 2024
Resumen:
Identifying and evaluating potential vaccine candidates has become one of the main objectives to combat tuberculosis. Among them, mannosylated Apa antigen from Mycobacterium tuberculosis and the non-mannosylated protein expressed in Escherichia coli, have been studied. Although both proteins can induce a protective response in mice, it has been considered that native protein can be dispensed. In this work, we study the protective response induced by Apa expressed in E. coli and in Streptomyces lividans. The latter, like native is secreted as a double band of 45/47 kDa, however, only its 47 kDa band is mannosylated. Both antigens and BCG were intranasal administrated in mice, and animals were then challenged by aerosol with M. tuberculosis H37Rv. The results showed that both, Apa from S. lividans and E. coli conferred statistically significantly protection to animals compared to controls. The cytokine immune response was studied by an immunoassay after animals' immunization, revealing that Apa from S. lividans induced a statistically significant proliferation of T cell, as well as the expression of IFN-gamma, IL-1 beta, IL-17 and IL-10. In contrast, non-proliferation was obtained with non-mannosylated protein, but induction of IL-12 and IL-17 was observed. Together, these results demonstrate that both proteins were able to modulate a specific immune response against M. tuberculosis, that could be driven by different mechanisms possibly associated with the presence or not of mannosylation. Furthermore, stimulation of cells from BCG-vaccinated animals with the proteins could be an important tool, to help define the use of a given subunit-vaccine after BCG vaccination.
Filiaciones:
Univ Nacl Autonoma Mexico, Dept Inmunol, Inst Invest Biomed, Mexico City 04510, Mexico
Univ Nacl Autonoma Mexico, Dept Inmunol, Catedrat CONAHCYT, Inst Invest Biomed, Mexico City 04510, Mexico
Univ Cuenca, Escuela Med Vet & Zootecnia, Fac Ciencias Agr, Cuenca 010205, Ecuador
Univ Nacl Autonoma Mexico, Fac Med Vet & Zootecnia, Dept Patol, Mexico City 04510, Mexico
Univ Nacl Autonoma Mexico, Dept Biol Mol & Biotecnol, Inst Invest Biomed, Mexico City 04510, Mexico
Green Accepted, hybrid, All Open Access; Hybrid Gold Open Access
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