MVA-B(Hospital Clinic of Barcelona)(MVA-B(Hospital Clinic of Barcelona))

概要

基本信息

药物类型

生物药

别名-

靶点-

作用机制-

治疗领域

免疫系统疾病感染泌尿生殖系统疾病

在研适应症-

非在研适应症

HIV感染

原研机构

Hospital Clínic de Barcelona

在研机构-

非在研机构

Hospital Clínic de Barcelona

最高研发阶段无进展临床1期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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关联

2

项与 MVA-B(Hospital Clinic of Barcelona) 相关的临床试验

PER-073-13 / Unknown status临床1期

A PHASE IB CLINICAL TRIAL TO ASSESS THE SAFETY AND IMMUNOGENICITY OF MVA-B IMMUNISATIONS ADMINISTERED VIA THE INTRAMUSCULAR AND TRANSCUTANEOUS ROUTES IN HEALTHY MALE AND FEMALE VOLUNTEERS

开始日期2014-01-07

申办/合作机构

Asociación Civil Impacta Salud y Educación

NCT00679497 / Completed临床1期IIT

A Phase I Study of MVA-B in Healthy Volunteers at Low Risk of HIV Infection

The purpose of this clinical trial is to study a modified pox viral vector considering:
HIV subtype B accounts for the most frequent virus strain in Europe and North America, as well as in many parts of the world.
This novel vaccinia construct expressing HIV subtype B gag, pol, env and nef antigens is to be studied in humans for the first time.

开始日期2008-06-01

申办/合作机构

Hospital Clínic de Barcelona

100 项与 MVA-B(Hospital Clinic of Barcelona) 相关的临床结果

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100 项与 MVA-B(Hospital Clinic of Barcelona) 相关的转化医学

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100 项与 MVA-B(Hospital Clinic of Barcelona) 相关的专利（医药）

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29

项与 MVA-B(Hospital Clinic of Barcelona) 相关的文献（医药）

2023-01-01·Frontiers in cellular and infection microbiology

An MVA-based vector expressing cell-free ISG15 increases IFN-I production and improves HIV-1-specific CD8 T cell immune responses.

Article

作者: Albert, Manuel ; Coloma, Rocio ; Falqui, Michela ; Marcos-Villar, Laura ; McGrail, Joseph Patrick ; Esteban, Mariano ; Gómez, Carmen Elena ; Sorzano, Carlos Óscar S ; Guerra, Susana ; Perdiguero, Beatriz

The human immunodeficiency virus (HIV), responsible of the Acquired Immune Deficiency Syndrome (AIDS), continues to be a major global public health issue with any cure or vaccine available. The Interferon-stimulated gene 15 (ISG15) encodes a ubiquitin-like protein that is induced by interferons and plays a critical role in the immune response. ISG15 is a modifier protein that covalently binds to its targets via a reversible bond, a process known as ISGylation, which is the best-characterized activity of this protein to date. However, ISG15 can also interact with intracellular proteins via non-covalent binding or act as a cytokine in the extracellular space after secretion. In previous studies we proved the adjuvant effect of ISG15 when delivered by a DNA-vector in heterologous prime-boost combination with a Modified Vaccinia virus Ankara (MVA)-based recombinant virus expressing HIV-1 antigens Env/Gag-Pol-Nef (MVA-B). Here we extended these results evaluating the adjuvant effect of ISG15 when expressed by an MVA vector. For this, we generated and characterized two novel MVA recombinants expressing different forms of ISG15, the wild-type ISG15GG (able to perform ISGylation) or the mutated ISG15AA (unable to perform ISGylation). In mice immunized with the heterologous DNA prime/MVA boost regimen, the expression of the mutant ISG15AA from MVA-Δ3-ISG15AA vector in combination with MVA-B induced an increase in the magnitude and quality of HIV-1-specific CD8 T cells as well as in the levels of IFN-I released, providing a better immunostimulatory activity than the wild-type ISG15GG. Our results confirm the importance of ISG15 as an immune adjuvant in the vaccine field and highlights its role as a potential relevant component in HIV-1 immunization protocols.

2018-01-02·Human Vaccines & Immunotherapeutics3区 · 医学

Sequential administration of MVA-based vaccines and PD-1/PD-L1-blocking antibodies confers measurable benefits on tumor growth and survival: Preclinical studies with MVA-βGal and MVA-MUC1 (TG4010) in a murine tumor model

3区 · 医学

Article

作者: Nourtier, Virginie ; Sansas, Benoit ; Hortelano, Julie ; Remy-Ziller, Christelle ; Bendjama, Kaïdre ; Gantzer, Murielle ; Claudepierre, Marie-Christine ; Préville, Xavier ; Rittner, Karola ; Quemeneur, Eric ; Thioudellet, Christine

TG4010, a Modified Vaccinia virus Ankara (MVA) expressing human mucin1 (MUC1) has demonstrated clinical benefit for patients suffering from advanced non-small cell lung cancer (NSCLC) in combination with chemotherapy. To support its development, preclinical experiments were performed with either TG4010 or β-galactosidase-encoding MVA vector (MVA-βgal) in mice presenting tumors in the lung. Tumor growth was obtained after intravenous injection of CT26 murine colon cancer cells, engineered to express either MUC1 or βgal. Mice showed increased survival rates after repeated intravenous injections of TG4010 or MVA-βgal, compared to an empty MVA control vector. Treatment with MVA vectors led to the accumulation of CD3^dimCD8^dim T cells, with two subpopulations characterized as KLRG1⁺CD127^- short-lived effector cells (SLECs), and KLRG1^-CD127^- early effector cells (EECs) comprising cells releasing IFNγ, Granzyme B and CD107a upon antigen-specific peptide stimulation. EECs were characterized by an up-regulation of PD-1. Tumor growth in the diseased lung correlated with the appearance of PD1⁺ Treg cells that partially disappeared after TG4010 treatment. At late stage of tumor development in the lung, PD-L1 was detected on CD45^- tumor cells, on CD4⁺ cells, including Treg cells, on CD3⁺CD8⁺ and CD3^dimCD8^dim T lymphocytes, on NK cells, on MDSCs and on alveolar macrophages. We demonstrated that targeting the PD-1/PD-L1 pathway with blocking monoclonal antibodies several days after TG4010 treatment, at late stage of tumor development, enhanced the therapeutic protection induced by the vaccine, supporting the ongoing clinical evaluation of TG4010 immunotherapy in combination with Nivolumab.

2016-02-20·AIDS2区 · 医学

Balance between activation and regulation of HIV-specific CD8+ T-cell response after modified vaccinia Ankara B therapeutic vaccination

2区 · 医学

Article

作者: Brander, Christian ; Ligos, Jose M. ; Mothe, Beatriz ; Esteban, Mariano ; Benito, Jose M. ; Montoya, Maria ; Rallon, Norma ; Plana, Montserrat ; Lopez Bernaldo de Quiros, Juan C. ; Garcia, Felipe ; Munoz-Fernandez, Maria A.

BACKGROUNDThe causes of HIV-vaccines failure are poorly understood. Therapeutic vaccination with modified vaccinia Ankara (MVA)-B in HIV-1-infected individuals did not control the virus upon analytical treatment interruption (ATI). We investigated whether the functional characteristics of HIV-specific CD8 T-cell responses stimulated by this vaccine, and the level of exhaustion of these cells might explain these results.METHODSTwenty-one HIV-1 chronically infected patients on combination antiretroviral therapy, included in the therapeutic vaccine trial RISVAC03, were studied: 13 immunized and eight controls. Functional characteristics, cytotoxic potential and exhaustion of HIV-specific CD8 T cells, were evaluated by polychromatic flow cytometry. Differences between groups were tested using nonparametric tests.RESULTSMVA-B vaccine induced an increase in HIV-specific CD8 T-cell response, but also increased their levels of exhaustion. At week 18 (following three immunizations) the level of response increased with respect to baseline (P = 0.02). A significant increase at weeks 18 and 24 (ATI) in granzyme B content was also observed. Interestingly, an increase in expression of exhaustion markers was found at weeks 18 (P = 0.006) and 24 (P = 0.01). However, there was no significant change in the functional profile of vaccine-induced CD8 cells. At week 36, in parallel to the rebound of plasma viremia after 12 weeks ATI, a significant increase in the level of CD8 response, in granzyme B content and in exhaustion markers expression, was observed in both groups.CONCLUSIONWe show that therapeutic vaccination with MVA-B tilts the balance between activation and regulation of the response of HIV-specific CD8 T cells towards regulation, which impacts on the viral rebound after ATI.

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
HIV感染	临床1期	西班牙	Hospital Clínic de Barcelona	2008-06-01

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT00679497 (RISVAC02, Pubmed \| Vaccine)	临床1期	-	30	MVA-B	鏇廠糧醖廠獵觸鬱獵艱(廠壓築壓膚觸繭餘餘網) = 壓獵衊糧廠廠艱鹹夢憲積觸選襯顧選願鹽鹹獵 (鬱鹹顧範簾鏇餘蓋餘衊 )	-	2011-10-26
TheraVac-02 (IAS2008)	N/A	HIV感染	10	MVA-B	(鏇鑰襯糧製鏇獵壓遞積) = 積鑰選窪壓襯艱網膚壓構製窪鏇製壓選襯夢壓 (艱糧糧糧膚憲選壓鹽願 ) 更多	-	2008-01-01