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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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 ; Sorzano, Carlos Óscar S ; Gómez, Carmen Elena ; 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.

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.

2015-06-01·Journal of Antimicrobial Chemotherapy2区 · 医学

Safety and immunogenicity of a modified vaccinia Ankara-based HIV-1 vaccine (MVA-B) in HIV-1-infected patients alone or in combination with a drug to reactivate latent HIV-1

2区 · 医学

Article

作者: Lucero, Constanza ; Climent, Nuria ; Cepeda, Victoria ; García, Felipe ; Puertas, María C. ; Rosàs, Miriam ; Benito, José M. ; Mothe, Beatriz ; Guardo, Alberto C. ; Brander, Christian ; Alvarez-Fernández, Carmen ; Gómez, Carmen Elena ; Alcamí, José ; Arnaiz, Joan Albert ; Perdiguero, Beatriz ; León, Agathe ; Alvarez, Carmen ; Sánchez, Sonsoles ; López Bernaldo de Quirós, Juan Carlos ; Muñoz-Fernández, María Angeles ; Blanco, Julià ; Jiménez, José Luis ; Torres, Berta ; Martinez-Picado, Javier ; Sánchez-Palomino, Sonsoles ; García-Arriaza, Juan ; Gatell, Jose M. ; Leal, Lorna ; Peña, José ; Gómez, Carmen E. ; Carrillo, Jorge ; Esteban, Mariano ; Jiménez, Laura ; Blanco, Juliá ; Rallón, Norma ; Gonzalez, Nuria ; Sánchez-Sorzano, Carlos Oscar ; Muñoz-Fernández, María Ángeles ; Pich, Judit ; Cobarsi, Patricia ; Clotet, Bonaventura ; Plana, Montserrat

AbstractObjectivesThe safety, immunogenicity, impact on the latent reservoir and rebound of viral load after therapeutic HIV-1 vaccination with recombinant modified vaccinia Ankara-based (MVA-B) HIV-1 vaccine expressing monomeric gp120 and the fused Gag-Pol-Nef polyprotein of clade B with or without a drug to reactivate latent HIV-1 (disulfiram) were assessed.MethodsHIV-1-infected patients were randomized to receive three injections of MVA-B (n = 20) or placebo (n = 10). Twelve patients (eight who received vaccine and four who were given placebo) received a fourth dose of MVA-B followed by 3 months of disulfiram. Combined ART (cART) was discontinued 8 weeks after the last dose of MVA-B. Clinical Trials.gov identifier: NCT01571466.ResultsMVA-B was safe and well tolerated. A minor, but significant, increase in the T cell responses targeting vaccine inserts of Gag was observed [a median of 290, 403 and 435 spot-forming-cells/106 PBMCs at baseline, after two vaccinations and after three vaccinations, respectively; P = 0.02 and P = 0.04]. After interruption of cART, a modest delay in the rebound of the plasma viral load in participants receiving vaccine but not disulfiram was observed compared with placebo recipients (P = 0.01). The dynamics of the viral load rebound did not change in patients receiving MVA-B/disulfiram. No changes in the proviral reservoir were observed after disulfiram treatment.ConclusionsMVA-B vaccination was a safe strategy to increase Gag-specific T cell responses in chronically HIV-1-infected individuals, but it did not have a major impact on the latent reservoir or the rebound of plasma viral load after interruption of cART when given alone or in combination with disulfiram.

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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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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


TheraVac-02 (IAS2008)	N/A	HIV感染	10	MVA-B	(範積遞壓糧蓋夢鑰餘憲) = 憲廠繭齋積廠鹹積遞蓋蓋網遞憲觸顧鬱窪鑰醖 (餘餘構選願蓋遞簾襯選 ) 更多	-	2008-01-01