Abstract:
:The tuberculosis (TB) vaccine MTBVAC is the only live-attenuated Mycobacterium tuberculosis (Mtb)-based vaccine in clinical development, and it confers superior protection in different animal models compared to the current vaccine, BCG (Mycobacterium bovis bacillus Calmette-Guérin). With the aim of using MTBVAC as a vector for a dual TB-HIV vaccine, we constructed the recombinant MTBVAC.HIVA2auxo strain. First, we generated a lysine auxotroph of MTBVAC (MTBVACΔlys) by deleting the lysA gene. Then the auxotrophic MTBVACΔlys was transformed with the E. coli-mycobacterial vector p2auxo.HIVA, harboring the lysA-complementing gene and the HIV-1 clade A immunogen HIVA. This TB-HIV vaccine conferred similar efficacy to the parental strain MTBVAC against Mtb challenge in mice. MTBVAC.HIVA2auxo was safer than BCG and MTBVAC in severe combined immunodeficiency (SCID) mice, and it was shown to be maintained up to 42 bacterial generations in vitro and up to 100 days after inoculation in vivo. The MTBVAC.HIVA2auxo vaccine, boosted with modified vaccinia virus Ankara (MVA).HIVA, induced HIV-1 and Mtb-specific interferon-γ-producing T cell responses and polyfunctional HIV-1-specific CD8+ T cells producing interferon-γ (IFN-γ), tumor necrosis factor alpha (TNF-α), and CD107a in BALB/c mice. Here we describe new tools to develop combined vaccines against TB and HIV with the potential of expansion for other infectious diseases.
journal_name
Mol Ther Methods Clin Devjournal_title
Molecular therapy. Methods & clinical developmentauthors
Broset E,Saubi N,Guitart N,Aguilo N,Uranga S,Kilpeläinen A,Eto Y,Hanke T,Gonzalo-Asensio J,Martín C,Joseph-Munné Jdoi
10.1016/j.omtm.2019.01.014subject
Has Abstractpub_date
2019-02-07 00:00:00pages
253-264issn
2329-0501pii
S2329-0501(19)30017-8journal_volume
13pub_type
杂志文章abstract::Vaccinia virus (VACV) was successfully used as a vaccine in the smallpox eradication campaign. Since then, it has been widely used in the development of vaccine and therapeutic vectors. However, methods of generating and purifying recombinant VACVs (rVACVs) are often time-consuming, cumbersome, and in some cases requi...
journal_title:Molecular therapy. Methods & clinical development
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abstract::rAAVrh74.MCK.GALGT2 is a surrogate gene therapy that inhibits muscular dystrophy in multiple animal models. Here, we report on a dose-response study of functional muscle GALGT2 expression as well as toxicity and biodistribution studies after systemic intravenous (i.v.) delivery of rAAVrh74.MCK.GALGT2. A dose of 4.3 × ...
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journal_title:Molecular therapy. Methods & clinical development
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journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
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journal_title:Molecular therapy. Methods & clinical development
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journal_title:Molecular therapy. Methods & clinical development
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journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
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journal_title:Molecular therapy. Methods & clinical development
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journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章,评审
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更新日期:2017-03-18 00:00:00
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journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
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更新日期:2016-05-11 00:00:00
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journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
doi:10.1016/j.omtm.2020.11.013
更新日期:2020-11-20 00:00:00
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journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
doi:10.1016/j.omtm.2018.10.012
更新日期:2018-12-05 00:00:00
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journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
doi:10.1016/j.omtm.2017.11.002
更新日期:2017-11-07 00:00:00
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journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
doi:10.1016/j.omtm.2018.06.005
更新日期:2018-07-23 00:00:00
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journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
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abstract::[This corrects the article DOI: 10.1038/mtm.2015.16.]. ...
journal_title:Molecular therapy. Methods & clinical development
pub_type: 已发布勘误
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journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
doi:10.1016/j.omtm.2018.04.004
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journal_title:Molecular therapy. Methods & clinical development
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abstract::Preclinical studies have demonstrated that a single injection of an adeno-associated virus (AAV) vector into the cerebrospinal fluid (CSF) can achieve widespread gene transfer throughout the central nervous system. Successfully translating this approach to humans requires identifying factors that influence AAV distrib...
journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
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abstract::Recombinant adeno-associated virus (rAAV) is one of the main vectors used in gene therapy. An accurate genome titer is not only critical for clinical dosing, but also a prerequisite for many analytical assays for AAV product characterization. AAV genome titer is traditionally determined by qPCR; however, assay precisi...
journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
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更新日期:2020-10-01 00:00:00
abstract::Duchenne muscular dystrophy (DMD) is a fatal disease of striated muscle deterioration. A unique therapeutic approach for DMD is the use of synthetic membrane stabilizers to protect the fragile dystrophic sarcolemma against contraction-induced mechanical stress. Block copolymer-based membrane stabilizer poloxamer 188 (...
journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
doi:10.1038/mtm.2015.42
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abstract::Human immunodeficiency virus (HIV) is an attractive target for chimeric antigen receptor (CAR) therapy. CAR T cells have proved remarkably potent in targeted killing of cancer cells, and we surmised that CAR T cells could prove useful in eradicating HIV-infected cells. Toward this goal, we interrogate several neutrali...
journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
doi:10.1016/j.omtm.2020.09.014
更新日期:2020-09-28 00:00:00
abstract::Retroviral vectors, including those derived from gammaretroviruses and lentiviruses, have found their way into the clinical arena and demonstrated remarkable efficacy for the treatment of immunodeficiencies, leukodystrophies, and globinopathies. Despite these successes, gene therapy unfortunately also has had to face ...
journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章,评审
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更新日期:2017-10-05 00:00:00
abstract::Crigler-Najjar syndrome is a severe metabolic disease of the liver due to a reduced activity of the UDP Glucuronosyltransferase 1A1 (UGT1A1) enzyme. In an effort to translate to the clinic an adeno-associated virus vector mediated liver gene transfer approach to treat Crigler-Najjar syndrome, we developed and optimize...
journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
doi:10.1038/mtm.2016.49
更新日期:2016-07-20 00:00:00
abstract::Adeno-associated virus (AAV) vectors have emerged as a safe and efficient gene therapy platform. One complication is that a significant amount of empty particles have always been generated as impurities during AAV vector production. However, the effects of such particles on AAV vector performance remain unclear. Here ...
journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
doi:10.1016/j.omtm.2016.12.004
更新日期:2016-12-24 00:00:00