Avaliação da ação terapêutica da vacina de DNA-hsp65 em um modelo de neurotuberculose

• Ano de defesa: 2021
• Autor(a) principal: Alcântara, Isabela Santos
• Orientador(a): Souza, Patrícia Rodrigues Marques de
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Programa de Pós-Graduação: Pós-Graduação em Biologia Parasitária
• Palavras-chave em Português: Tuberculose; Vacinas; Sistema nervoso central
• Palavras-chave em Inglês: Tuberculosis; Vaccine; Central nervous system; DNA vaccine
• Área do conhecimento CNPq: CIENCIAS BIOLOGICAS::PARASITOLOGIA
• Link de acesso: http://ri.ufs.br/jspui/handle/riufs/15717

Tuberculosis is a disease caused by Mycobacterium tuberculosis (Mtb) and is currently the leading cause of death from a single infectious agent, accounting for approximately 40% of deaths among people infected with the Human Immunodeficiency Virus (HIV). Tuberculosis in the Central Nervous System (CNS), also known as neurotuberculosis or tuberculous meningitis, results from the hematogenous spread of Mtb from the lung to the CNS and has a high mortality rate. One of the weapons against the disease is the BCG vaccine (Bacillus Calmette-Guérin), whose protection level is on average 60%. Due to the limitations presented by BCG, there have been substantial efforts in recent years for the development of new vaccines. A promising candidate is the recombinant DNA vaccine that encodes the heat shock protein, HSP65, which has shown both prophylactic and therapeutic effect in experimental Tuberculosis, until the present study the therapeutic effect of the DNA-hsp65 vaccine against Tuberculosis in the CNS had not been studied. Therefore, the therapeutic effect of the DNA-hsp65 vaccine on experimental neurotuberculosis was evaluated. For this, C57BL/6 mice were used and the stereotaxis protocol was performed for intracerebroventricular microinjection with the laboratory strain (H37Rv) of Mtb for induction of neurotuberculosis, after this procedure the animals were divided into three groups, where one of them was immunized only with the pVAX plasmid vector (Vector Group), another group received only PBS (PBS Group) and the third group was immunized with the pVAX-hsp65 plasmid DNA (Vaccinated Group). Two weeks after the last dose, the animals were euthanized and submitted to collection of brains and lungs for histological analysis and determination of the number of colony forming units (CFU). The results showed that the DNAhsp65 vaccine was not able to reduce the bacterial load in the organs of the animals, but induced a decrease in local inflammatory damage, demonstrating tissue preservation in both the brain and the lungs of the animals. In summary, immunotherapy with DNA-hsp65 showed an immunological regulatory role demonstrating an immunotherapeutic effect in CNS TB.