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Vacinas em desenvolvimento para a tuberculose
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A tuberculose é uma doença infeciosa, causada por espécies pertencentes ao complexo Mycobacterium tuberculosis. Esta doença altamente transmissível, constitui atualmente um dos maiores problemas de saúde pública, a nível mundial, sendo uma das que causa maior morbilidade e mortalidade, nomeadamente em países em vias de desenvolvimento.
Os indivíduos podem desenvolver doença, ou permanecer infetados, de forma assintomática, um estado em que não há transmissão e que se designa por tuberculose latente. A forma mais comum da doença, afeta o pulmão, uma vez que, o bacilo da tuberculose multiplica-se bem em tecidos bem oxigenados, onde irá desenvolver a infeção e ativação do sistema imunológico, dando origem a uma estrutura que a caracteriza, o granuloma. Pode ainda manifestar-se extrapulmonarmente, quando há disseminação dos bacilos da tuberculose pela circulação sanguínea, podendo todos órgãos serem atingidos. O sucesso do Mycobacterium tuberculosis deve-se, em grande parte, à capacidade de estabelecer um nicho de sobrevivência intracelular em macrófagos e de evadir as respostas imunes do hospedeiro.
A única vacina aprovada, o bacillus Calmette -Guérin é o método profilático disponível, para prevenir a tuberculose e este tem demonstrado eficácia na prevenção da forma meníngea, em recém-nascidos, mas a sua eficácia em adultos varia geograficamente.
Dada a complexidade da infeção, novas vacinas deverão ser desenhadas para induzir proteção de forma a atingi eficazmente os seus diferentes estádios, desde a primo-infeção à latência ou doença ativa. Além disso, em indivíduos infetados com o vírus da imunodeficiência humana, a co-infeção com Mycobacterium tuberculosis, é bastante frequente e em consequência essas novas vacinas em desenvolvimento deverão ser adequadas e seguras para doentes imunocomprometidos.
Nas últimas décadas, registaram-se progressos na investigação e desenvolvimento de vacinas contra a tuberculose. Assim, pretendeu-se com este trabalho fazer uma análise do estado-da-arte no desenvolvimento de novas vacinas em curso e as suas categorias, para a prevenção efetiva da tuberculose, incluindo vacinas para uso profilático, de reforço ou terapêutico.
Tuberculosis is an infectious disease caused by species belonging to the Mycobacterium tubercolosis complex. This highly transmissible disease is currently one of the world´s biggest public health problems, causing the greatest morbidity and mortality, particularly in developing countries. Individuals can develop the disease or remain infected asymptomatically, a state in which there is no transmission and which is known as latent tuberculosis. The most common form of the disease affects the lungs, since the tubercle bacillus multiplies well in well-oxiygenated tissues, where it will develop the infection and activate the immune system, giving rise to its characteristic structure, the granuloma. It can also manifest itself extrapulmonarily, when the tubercle bacilli spread through the bloodstream and all organs can be affected. The success of Mycobacterium tuberculosis is largely due to its ability to estabilish an intracellular survival niche in macrophages and evade the host´s immune responses. The only approved vaccine, bacillus Calmette-Guérin, is the prophylactic method available to prevent tuberculosis and it has shown efficacy in preventing the meningeal form in newborns, but its efficacy in adults varies geographically. Given the complexity of the infection, new vaccines should be designed to induce protection in order to effectively target its different stages, from early infection to latency or active disease. Futhermore, in individuals infected with the human immunodeficiency virus, co-infection with Mycobacterium tuberculosis is quite common and, as a result, these new vaccines under development should be suitable and safe for immunocompromised patients. In recent decades, progress has been made in research and development of vaccines against tuberculosis. The aim of this study was therefore to analyze the state of the art in the development of new vaccines and their categories for the effective prevention of tuberculosis, including vaccines for prophylactic, booster or therapeutic use.
Tuberculosis is an infectious disease caused by species belonging to the Mycobacterium tubercolosis complex. This highly transmissible disease is currently one of the world´s biggest public health problems, causing the greatest morbidity and mortality, particularly in developing countries. Individuals can develop the disease or remain infected asymptomatically, a state in which there is no transmission and which is known as latent tuberculosis. The most common form of the disease affects the lungs, since the tubercle bacillus multiplies well in well-oxiygenated tissues, where it will develop the infection and activate the immune system, giving rise to its characteristic structure, the granuloma. It can also manifest itself extrapulmonarily, when the tubercle bacilli spread through the bloodstream and all organs can be affected. The success of Mycobacterium tuberculosis is largely due to its ability to estabilish an intracellular survival niche in macrophages and evade the host´s immune responses. The only approved vaccine, bacillus Calmette-Guérin, is the prophylactic method available to prevent tuberculosis and it has shown efficacy in preventing the meningeal form in newborns, but its efficacy in adults varies geographically. Given the complexity of the infection, new vaccines should be designed to induce protection in order to effectively target its different stages, from early infection to latency or active disease. Futhermore, in individuals infected with the human immunodeficiency virus, co-infection with Mycobacterium tuberculosis is quite common and, as a result, these new vaccines under development should be suitable and safe for immunocompromised patients. In recent decades, progress has been made in research and development of vaccines against tuberculosis. The aim of this study was therefore to analyze the state of the art in the development of new vaccines and their categories for the effective prevention of tuberculosis, including vaccines for prophylactic, booster or therapeutic use.
Descrição
Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, 2024, Universidade de Lisboa, Faculdade de Farmácia.
Palavras-chave
Tuberculose Vacinas Ensaios clínicos Linfócitos T Citocinas Antigénios Mestrado integrado - 2024