Methods and clinical development of adenovirus-vectored vaccines against mucosal pathogens

Afkhami, Sam; Yao, Yushi; Xing, Zhou

doi:10.1038/mtm.2016.30

Cited by 90 publications

(104 citation statements)

References 90 publications

(146 reference statements)

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“…Adenovirus has a natural tropism for the mucosal epithelium, which makes it an ideal vector for vaccination against infections acquired via mucosal surfaces [19]. Intranasal immunization in different experimental settings has been reported to provide potent protection against intravaginal challenge [18, 20–22].…”

Section: Introductionmentioning

confidence: 99%

Chlamydial Type III Secretion System Needle Protein Induces Protective Immunity againstChlamydia muridarumIntravaginal Infection

Koroleva

Kobets

Щербинин

et al. 2017

BioMed Research International

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Chlamydia trachomatis imposes serious health problems and causes infertility. Because of asymptomatic onset, it often escapes antibiotic treatment. Therefore, vaccines offer a better option for the prevention of unwanted inflammatory sequelae. The existence of serologically distinct serovars of C. trachomatis suggests that a vaccine will need to provide protection against multiple serovars. Chlamydia spp. use a highly conserved type III secretion system (T3SS) composed of structural and effector proteins which is an essential virulence factor. In this study, we expressed the T3SS needle protein of Chlamydia muridarum, TC_0037, an ortholog of C. trachomatis CdsF, in a replication-defective adenoviral vector (AdTC_0037) and evaluated its protective efficacy in an intravaginal Chlamydia muridarum model. For better immune responses, we employed a heterologous prime-boost immunization protocol in which mice were intranasally primed with AdTC_0037 and subcutaneously boosted with recombinant TC_0037 and Toll-like receptor 4 agonist monophosphoryl lipid A mixed in a squalene nanoscale emulsion. We found that immunization with TC_0037 antigen induced specific humoral and T cell responses, decreased Chlamydia loads in the genital tract, and abrogated pathology of upper genital organs. Together, our results suggest that TC_0037, a highly conserved chlamydial T3SS protein, is a good candidate for inclusion in a Chlamydia vaccine.

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Section: Introductionmentioning

confidence: 99%

Chlamydial Type III Secretion System Needle Protein Induces Protective Immunity againstChlamydia muridarumIntravaginal Infection

Koroleva

Kobets

Щербинин

et al. 2017

BioMed Research International

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“…In fact, the first oncolytic virus was approved by US Food and Drug Administration (FDA), as a cancer treatment for advanced melanoma in 2015 . Adenoviruses have also shown a great potential fighting against infectious diseases . For these reasons different cell lines have been evaluated and are now available to produce adenoviruses being human embryonic kidney 293 (HEK293) cell line the most widely used cell line .…”

Section: Introductionmentioning

confidence: 99%

Establishing Suspension Cell Cultures for Improved Manufacturing of Oncolytic Adenovirus

Moreira

Silva

Sousa

et al. 2020

Biotechnology Journal

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Recent clinical trials have shown the potential of oncolytic adenoviruses as a cancer immunotherapy. A successful transition of oncolytic adenovirus to clinical applications requires efficient and good manufacturing practice compatible production and purification bioprocesses. Suspension cultures are preferable for virus production as they can reduce process costs and increase product quality and consistency. This work describes the adaptation of the A549 cell line to suspension culture in serum‐reduced medium validated by oncolytic adenovirus production in stirred tank bioreactor. Cell concentrations up to 3 × 106 cells mL−1 are obtained during the production process. At harvest 1.4 × 1010 infectious particles mL−1 and 6.9 ± 1.1 × 1010 viral genome mL−1 are obtained corresponding to a viral genome: infectious particles ratio of 5.2 (± 1.9): 1 confirming the virus quality. Overall, the suspension characteristics of these A549 cells support an easily scalable, less time‐consuming, and more cost‐effective process for expanded success in the use of oncolytic viruses for cancer therapy.

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“…A terapia gênica faz uso de genes ao invés de drogas para o tratamento de doenças 1 . A facilidade na manipulação de vetores e a grande evolução na área da genética tornaram a terapia gênica uma alternativa ao tratamento convencional para resolver problemas complexos relacionados à saúde humana, como a cura de doenças genéticas herdadas, ou de doenças contraídas ao longo da vida 2 . Desta forma, a terapia gênica utiliza técnicas de DNA recombinante para construir a sequência gênica dentro de um vírus que será o doador deste material nas células do paciente 3 .…”

Section: -Introduçãounclassified

Uso de vírus adeno-associado: um avanço na terapia gênica

Colombo¹,

Melo²,

Matter³

2017

RICSB

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ResumoA terapia gênica utiliza técnicas de engenharia genética para interferir na origem de uma doença. Nesta técnica introduz-se uma sequência de DNA codificante nas células do paciente como tratamento para a correção de um problema recorrente devido a um gene mutado. O uso de vetores virais recombinantes para introduzir o gene correto no indivíduo tem se mostrado bastante desafiador e promissor. Este artigo tem como objetivo apresentar de forma atualizada os conceitos básicos e as perspectivas da terapia gênica para doenças as doenças: fibrose cística, artrite reumatoide, hemofilia e dislipidemia (deficiência da lipoproteína lipase) utilizando o vírus adeno-associado (VAA) como vetor doador do novo gene. Os avanços obtidos no emprego desta técnica, como método de tratamento, podem contribuir largamente para a otimização da terapêutica e, consequentemente, melhorar a qualidade de vida de pacientes portadores de diferentes doenças incuráveis. Neste sentido, os VAA têm se mostrado tecnologicamente versáteis, seguros e efetivos veículos no procedimento.Palavras-chave: terapia gênica, vírus adeno-associado, fibrose cística, artrite reumatóide, hemofilia, LPLD. AbstractGene therapy uses genetic engineering techniques to interfere with the origin of a disease. In this technique a DNA coding sequence is introduced into the patient's cells as treatment for the correction of a recurring problem due to a mutated gene. The use of recombinant viral vectors to introduce the correct gene into the patient has shown to be quite challenging and promising approach. This article aims to update the basic concepts and the perspectives of gene therapy for diseases such as cystic fibrosis, rheumatoid arthritis, hemophilia and dyslipidemia (lipoprotein lipase deficiency) using adenoassociated virus (AAV) as the donor vector of the new gene. The advances obtained with the use of this technique as a treatment can contribute greatly to the optimization of the therapy and, consequently, improve the life quality of patients with different incurable diseases. In this way, AAV has proven to be technologically versatile, safe and effective vehicles in the procedure.

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Methods and clinical development of adenovirus-vectored vaccines against mucosal pathogens

Cited by 90 publications

References 90 publications

Chlamydial Type III Secretion System Needle Protein Induces Protective Immunity againstChlamydia muridarumIntravaginal Infection

Chlamydial Type III Secretion System Needle Protein Induces Protective Immunity againstChlamydia muridarumIntravaginal Infection

Establishing Suspension Cell Cultures for Improved Manufacturing of Oncolytic Adenovirus

Uso de vírus adeno-associado: um avanço na terapia gênica

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