Dataset Information

Two doses of candidate TB vaccine MVA85A in antiretroviral therapy (ART) naive subjects gives comparable immunogenicity to one dose in ART+ subjects.

ABSTRACT: Tuberculosis (TB) is a global public health problem exacerbated by the HIV epidemic. Here we evaluate a candidate TB vaccine, MVA85A, in a Phase I study in HIV-infected adults in Senegal. 24 patients were enrolled: Group 1?12, antiretroviral therapy (ART) naïve, adults, with CD4 counts >300 and HIV RNA load <100,000 copies/ml. Group 2?12 adults, stable on ART, with CD4 counts >300, and an undetectable HIV RNA load. Safety was evaluated by occurrence of local and systemic adverse events (AEs) and by monitoring of CD4 count, HIV RNA load, haematology and biochemistry. Immunogenicity was evaluated by ex-vivo interferon-gamma ELISpot assay. 87.7% of AEs were mild; 11.6% were moderate; and 0.7% were severe. 29.2% of AEs were systemic; 70.8% were expected local AEs. There were no vaccine-related Serious Adverse Events (SAEs) or clinically significant effects on HIV RNA load or CD4 count. In ART naive subjects, the first MVA85A immunisation induced a significant immune response at 1 and 4 weeks post-immunisation, which contracted to baseline by 12 weeks. Durability of immunogenicity in subjects on ART persisted out to 24 weeks post-vaccination. A second dose of MVA85A at 12 months enhanced immunogenicity in ART naïve subjects. Subjects on ART had higher responses after the first vaccination compared with ART naïve subjects; responses were comparable after 2 immunisations. In conclusion, MVA85A is well-tolerated and immunogenic in HIV-infected subjects in Senegal. A two dose regimen in ART naïve subjects is comparable in immunogenicity to a single dose in subjects on ART. Clinicaltrials.gov trial identifier NCT00731471.

SUBMITTER: Dieye TN

PROVIDER: S-EPMC3696007 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Two doses of candidate TB vaccine MVA85A in antiretroviral therapy (ART) naïve subjects gives comparable immunogenicity to one dose in ART+ subjects.

Dieye Tandakha N TN Ndiaye Birahim P BP Dieng Alle B AB Fall Marema M Brittain Nathaniel N Vermaak Samantha S Camara Makhtar M Diop-Ndiaye Halimatou H Ngom-Gueye Ndeye Fatou NF Diaw Papa A PA Toure-Kane Coumba C Sow Papa S PS Mboup Souleymane S McShane Helen H

PloS one 20130628 6

Tuberculosis (TB) is a global public health problem exacerbated by the HIV epidemic. Here we evaluate a candidate TB vaccine, MVA85A, in a Phase I study in HIV-infected adults in Senegal. 24 patients were enrolled: Group 1∶12, antiretroviral therapy (ART) naïve, adults, with CD4 counts >300 and HIV RNA load <100,000 copies/ml. Group 2∶12 adults, stable on ART, with CD4 counts >300, and an undetectable HIV RNA load. Safety was evaluated by occurrence of local and systemic adverse events (AEs) and ...[more]

PMID: 23840618

Similar Datasets

Project description:OBJECTIVES:To investigate the safety and immunogenicity of a booster BCG vaccination delivered intradermally in healthy, BCG vaccinated subjects and to compare with a previous clinical trial where BCG vaccinated subjects were boosted with a new TB vaccine, MVA85A. DESIGN:Phase I open label observational trial, in the UK. Healthy, HIV-negative, BCG vaccinated adults were recruited and vaccinated with BCG. The primary outcome was safety; the secondary outcome was cellular immune responses to antigen 85, overlapping peptides of antigen 85A and tuberculin purified protein derivative (PPD) detected by ex vivo interferon-gamma (IFN-gamma) ELISpot assay and flow cytometry. RESULTS AND CONCLUSIONS:BCG revaccination (BCG-BCG) was well tolerated, and boosting of pre-existing PPD-specific T cell responses was observed. However, when these results were compared with data from a previous clinical trial, where BCG was boosted with MVA85A (BCG-MVA85A), MVA85A induced significantly higher levels (>2-fold) of antigen 85-specific CD4+ T cells (both antigen and peptide pool responses) than boosting with BCG, up to 52 weeks post-vaccination (p = 0.009). To identify antigen 85A-specific CD8+ T cells that were not detectable by ex vivo ELISpot and flow cytometry, dendritic cells (DC) were used to amplify CD8+ T cells from PBMC samples. We observed low, but detectable levels of antigen 85A-specific CD8+ T cells producing IFNgamma (1.5% of total CD8 population) in the BCG primed subjects after BCG boosting in 1 (20%) of 5 subjects. In contrast, in BCG-MVA85A vaccinated subjects, high levels of antigen 85A-specific CD8+ T cells (up to 14% total CD8 population) were observed after boosting with MVA85A, in 4 (50%) of 8 subjects evaluated. In conclusion, revaccination with BCG resulted in modest boosting of pre-existing immune responses to PPD and antigen 85, but vaccination with BCG-MVA85A induced a significantly higher response to antigen 85 and generated a higher frequency of antigen 85A-specific CD8+ T cells. TRIAL REGISTRATION:ClinicalTrials.gov NCT00654316 NCT00427830.

Project description:BackgroundVaccination against tuberculosis (TB) should provide long-term protective immunity against Mycobacterium tuberculosis (M.tb). The current TB vaccine, Bacille Calmette-Guerin (BCG), protects against disseminated childhood TB, but protection against lung TB in adolescents and adults is variable and mostly poor. One potential reason for the limited durability of protection may be waning of immunity through gradual attrition of BCG-induced T cells. We determined if a MVA85A viral-vector boost could enhance the durability of mycobacteria-specific T cell responses above those induced by BCG alone.MethodsWe describe a long-term follow-up study of persons previously vaccinated with MVA85A. We performed a medical history and clinical examination, a tuberculin skin test and measured vaccine-specific T cell responses in persons previously enrolled as adults, adolescents, children or infants into three different Phase II trials, between 2005 and 2011.ResultsOf 252 potential participants, 183 (72.6%) consented and completed the study visit. Vaccine-induced Ag85A-specific CD4+ T cell responses were remarkably persistent in healthy, HIV-uninfected adults, adolescents, children and infants, up to 6 years after MVA85A vaccination. Specific CD4+ T cells expressed surface markers consistent with either CD45RA-CCR7+ central memory or CD45RA-CCR7- effector memory T cells. Similarly durable Ag85A-specific CD4+ T cell responses were detected in HIV-infected persons who were on successful antiretroviral therapy when MVA85A was administered. By contrast, Ag85A-specific CD4+ T cell frequencies in untreated MVA85A-vaccinated HIV-infected persons were mostly undetectable 3-5 years after vaccination.ConclusionMVA85A induces remarkably durable T cell responses in immunocompetent persons. However, results from a recent phase IIb trial of MVA85A, conducted in infants from the same geographic area and study population, showed no vaccine efficacy, suggesting that these durable T cell responses do not enhance BCG-induced protection against TB in infants.

Project description:BackgroundPatients with human immunodeficiency virus (HIV) are at a significantly higher risk of cardiovascular disease (CVD) compared to HIV-negative people. Left heart dysfunction is the most common cardiac complication in people living with HIV/acquired immune deficiency syndrome (PLWHA), and diastolic dysfunction is an important predictor of cardiovascular events. The aims of this study were (1) to detect changes in left cardiac structure and function in antiretroviral therapy (ART)-naive PLWHA using echocardiography; and (2) to investigate the risk factors for the development of left ventricular diastolic dysfunction (LVDD) in ART-naive PLWHA.MethodsWe retrospectively included 105 ART-naïve PLWHA and included 90 healthy subjects as controls to compare the differences in left heart structure and function between the two groups. Univariate and multifactorial logistic regression were employed to explore the risk factors of the development of LVDD in ART-naive PLWHA.ResultsThe left ventricular end-diastolic internal diameter (LVEDD), left ventricular mass index (LVMI), and left atrial volume index (LAVI) were significantly greater in PLWHA than in controls (p < .05). The E/A ratio, lateral e' velocity, and mitral deceleration time were significantly lower in PLWHA than in controls (p < .05). Average E/e' ratio was significantly higher in PLWHA than in controls (p < .05). Left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) were not significantly different between PLWHA and controls (p > .05). Multifactorial logistic regression analysis showed that age, body mass index (BMI), and CD4+ count <200 cells/μL were independent risk factors for LVDD in ART-naive PLWHA (OR = 1.781, 1.228, 3.683, p < .05).ConclusionsLeft ventricular systolic function did not differ between PLWHA and controls, and left ventricular diastolic function was lower in PLWHA than in controls. Age, BMI, and CD4+ count were independent factors affecting LVDD in ART-naive PLWHA.

Dataset Information

Two doses of candidate TB vaccine MVA85A in antiretroviral therapy (ART) naive subjects gives comparable immunogenicity to one dose in ART+ subjects.

Publications

Two doses of candidate TB vaccine MVA85A in antiretroviral therapy (ART) naïve subjects gives comparable immunogenicity to one dose in ART+ subjects.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets