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PLoS One ; 12(2): e0171677, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28192534

RESUMO

Schistosomiasis is a neglected parasitic disease of major public health concern as it affects over 250 million people in developing countries. Currently there is no licensed vaccine available against schistosomiasis. The Schistosoma mansoni calpain protein, Sm-p80, is a leading vaccine candidate now ready to move to clinical trials. In order to better assess Sm-p80 vaccine immunogenicity; here we used a systems biology approach employing RNA-sequencing to identify gene signatures and epistatic interactions following Sm-p80 vaccination in mouse and baboon models that may predict vaccine efficacy. Recombinant Sm-p80 + CpG-oligodeoxynucleotide (ODN) vaccine formulation induced both cellular and humoral immunity genes with a predominant TH1 response as well as TH2 and TH17 gene signatures. Early gene responses and gene-network interactions in mice immunized with rSm-p80 + ODN appear to be initiated through TLR4 signaling. CSF genes, S100A alarmin genes and TNFRSF genes appear to be a signature of vaccine immunogenicity/efficacy as identified by their participation in gene network interactions in both mice and baboons. These gene families may provide a basis for predicting desirable outcomes for vaccines against schistosomiasis leading to a better understanding of the immune system response to vaccination.


Assuntos
Antígenos de Helmintos/imunologia , Schistosoma mansoni/imunologia , Esquistossomose mansoni/imunologia , Vacinas/imunologia , Animais , Anticorpos Anti-Helmínticos/imunologia , Epistasia Genética/genética , Epistasia Genética/imunologia , Feminino , Redes Reguladoras de Genes/genética , Redes Reguladoras de Genes/imunologia , Imunidade Celular/genética , Imunidade Celular/imunologia , Imunidade Humoral/genética , Imunidade Humoral/imunologia , Masculino , Camundongos Endogâmicos C57BL , Oligodesoxirribonucleotídeos/administração & dosagem , Oligodesoxirribonucleotídeos/imunologia , Papio , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Schistosoma mansoni/metabolismo , Schistosoma mansoni/fisiologia , Esquistossomose mansoni/parasitologia , Esquistossomose mansoni/prevenção & controle , Transdução de Sinais/genética , Transdução de Sinais/imunologia , Transcriptoma/genética , Transcriptoma/imunologia , Vacinação/métodos , Vacinas/administração & dosagem
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