O OMPeoma de Treponema pallidum e a busca por uma vacina contra sífilis.
DOI:
https://doi.org/10.5327/DST-2177-8264-1480Resumo
Apesar de mais de um século de investigação, o desenvolvimento de uma vacina contra a sífilis tem sido historicamente dificultado pela membrana externa incomum de Treponema pallidum subsp. pallidum (TPA) e pela incapacidade de propagar a espiroqueta in vitro. Observações iniciais utilizando o modelo animal coelho demonstraram que uma imunidade protetora mediada por anticorpos é possível. A recente descoberta do repertório de proteínas de membrana externa (OMPs) de TPA definiu os possiveis alvos de anticorpos protetores e promoveu a base para o desenvolvimento atual de vacinas contra sífilis. Baseando-se em uma abordagem denominada “Learning from nature”, o mapeamento dos anticorpos induzidos durante a infecção natural contra as OMPs permitiu a identificação e priorização de loops extracelulares (ECLs) como alvos vacinais. A imunização de animais com scaffolds proteicos exibindo esses alvos gera títulos elevados de anticorpos capazes de reconhecer regiões expostas na superfície do espiroqueta. Avanços recentes no cultivo in vitro de longo prazo e na manipulação genética de TPA possibilitaram o desenvolvimento de ensaios para avaliar diretamente a atividade funcional desses anticorpos na promoção da opsonofagocitose, inibição do crescimento, comprometimento da motilidade e ruptura da membrana externa. Plataformas de segunda geração estão sendo exploradas para aumentar a imunogenicidade, simplificar a produção e facilitar a escalabilidade desses imunógenos até ensaios clínicos. Paralelamente, pesquisadores estão identificando a variabilidade da sequência de OMPs entre cepas circulantes de TPA para compreender como mutações podem afetar a ligação de anticorpos e a eficácia global da vacina. Coletivamente, esses avanços posicionam estrategicamente o campo para englobar conhecimentos estruturais, imunológicos e microbiológicos, visando finalmente, alcançar uma vacina eficaz contra a sífilis.
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