RESUMO
Respiratory syncytial virus (RSV) infection is a common cause of hospitalisation in infants and the elderly. Palivizumab prophylaxis is the only approved treatment modality but is costly and only offered to select vulnerable populations. Here, we investigated gene delivery approaches via recombinant adeno-associated virus (rAAV2/8) and simian immunodeficiency virus (rSIV.F/HN) vectors to achieve sustained in vivo production of palivizumab in a murine model. Delivery of palivizumab-expressing vectors 28 days prior to RSV challenge resulted in complete protection from RSV-induced weight loss. This approach offers prophylaxis against RSV infection, allowing for wider use and reduction in treatment costs in vulnerable populations.
Assuntos
Anticorpos Monoclonais Humanizados/genética , Expressão Gênica , Terapia Genética , Palivizumab/genética , Infecções por Vírus Respiratório Sincicial/terapia , Infecções por Vírus Respiratório Sincicial/virologia , Vírus Sinciciais Respiratórios , Animais , Dependovirus/genética , Modelos Animais de Doenças , Feminino , Técnicas de Transferência de Genes , Engenharia Genética , Vetores Genéticos/administração & dosagem , Vetores Genéticos/genética , Injeções Intramusculares , Lentivirus/genética , Camundongos , Infecções por Vírus Respiratório Sincicial/imunologia , Vírus Sinciciais Respiratórios/imunologia , Transdução Genética , Resultado do TratamentoRESUMO
Integrons are genetic elements capable of capturing and expressing open reading frames (ORFs) embedded within gene cassettes. They are involved in the dissemination of antibiotic resistance genes (ARGs) in clinically important pathogens. Although the ARGs are common in the oral cavity the association of integrons and antibiotic resistance has not been reported there. In this work, a PCR-based approach was used to investigate the presence of integrons and associated gene cassettes in human oral metagenomic DNA obtained from both the UK and Bangladesh. We identified a diverse array of gene cassettes containing ORFs predicted to confer antimicrobial resistance and other adaptive traits. The predicted proteins include a putative streptogramin A O-acetyltransferase, a bleomycin binding protein, cof-like hydrolase, competence and motility related proteins. This is the first study detecting integron gene cassettes directly from oral metagenomic DNA samples. The predicted proteins are likely to carry out a multitude of functions; however, the function of the majority is yet unknown.
