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Avalia????o de vacinas recombinantes contra a leptospirose

By Michel Quevedo FAGUNDES

Abstract

A leptospirose ?? considerada um problema global para a sa??de p??blica e veterin??ria. No Brasil, a enfermidade possui maior impacto em popula????es vulner??veis, as quais est??o distribu??das nas favelas das grandes cidades, onde tradicionalmente ocorre elevada morbidade e mortalidade. Desta forma, torna-se necess??rio o estabelecimento de novas efetivas de interven????o para a redu????o dos casos. As vacinas dispon??veis para a preven????o da enfermidade em humanos e animais s??o comprovadamente limitadas, j?? que induzem imunidade pouco duradoura e sorovar-espec??fica, al??m de provocarem efeitos colaterais. Novas estrat??gias para o desenvolvimento de uma vacina contra a leptospirose t??m sido empregadas, como a caracteriza????o de prote??nas recombinantes, a constru????o de vacinas de DNA e o teste de novos adjuvantes para modula????o da resposta imune. Neste contexto, as prote??nas de membrana externa LipL32, LigB e LigA foram selecionadas para este trabalho, pois s??o conservadas e encontradas somente entre sorovares patog??nicos de Leptospira. Assim, os genes lipL32 e ligA foram clonados no vetor de express??o em eucariotos pVAX para a obten????o de vacinas de DNA, e as prote??nas rLigBNI e rLipL32 foram testadas utilizando o pr??polis como co-adjuvante na forma de vacinas de subunidade. Ap??s a produ????o das vacinas, hamsters foram vacinados e a resposta imune foi avaliada atrav??s de ELISA, qPCR e desafio. Dentre as prepara????es testadas, a resposta imune teve n??veis mais elevados e significativos para a vacina de DNA contendo o gene lipL32 e para a vacina de subunidade de LigBNI. Al??m disso, estas vacinas foram capazes de proteger significativamente os animais contra o desafio hom??logo, mostrando o potencial destas formula????es para o desenvolvimento de uma vacina recombinante para a leptospirose.Leptospirosis is considered a global problem regarding both veterinary medicine and public health. In Brazil, the disease has greater impact in vulnerable populations, living in slums of great cities, where high morbidity and mortality occur. This situation requires the establishment of new intervention policies in order to reduce cases. Available vaccines to prevent the disease in humans and animals are notoriously underachieving, producing short term, serovar specific protection and collateral effects. New strategies are being employed to develop novel vaccines against leptospirosis, such as the characterization of recombinant proteins, construction of DNA vaccines, and use of alternative adjuvants. Surface exposed proteins LipL32, LigB, and LigA are highly conserved and found only in pathogenic serovars, therefore these were selected to be used in this study. LigA and LipL32 genes were cloned into the pVAX eukaryote expression vector to be used as DNA vaccines. rLigBNI and rLipL32 were assessed as subunit recombinant antigens using propolis as a co-adjuvant. Hamsters were immunized and the response was assessed through qPCR, ELISA, and lethal challenge. DNA vaccine containing the LipL32 gene, and the subunit rLigBNI vaccine had the highest results in the immune-stimulation assays. Furthermore, these imunogens were able to significantly protect animals against lethal challenge, demonstrating their potential for leptospirosis vaccine development

Topics: leptospirose, prote??nas recombinantes, vacinas de DNA, pr??polis, leptospirosis, recombinant vaccines, DNA vaccines, propolis, CNPQ::CIENCIAS BIOLOGICAS::IMUNOLOGIA
Publisher: Universidade Federal de Pelotas
Year: 2012
OAI identifier: oai:agregador.ibict.br.RI_UFPEL:oai:repositorio.ufpel.edu.br:123456789/1220
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