Agency: European Commission | Branch: H2020 | Program: RIA | Phase: PHC-08-2014 | Award Amount: 25.06M | Year: 2015
The TBVAC2020 proposal builds on the highly successful and long-standing collaborations in subsequent EC-FP5-, FP6- and FP7-funded TB vaccine and biomarker projects, but also brings in a large number of new key partners from excellent laboratories from Europe, USA, Asia, Africa and Australia, many of which are global leaders in the TB field. This was initiated by launching an open call for Expressions of Interest (EoI) prior to this application and to which interested parties could respond. In total, 115 EoIs were received and ranked by the TBVI Steering Committee using proposed H2020 evaluation criteria. This led to the prioritisation of 52 R&D approaches included in this proposal. TBVAC2020 aims to innovate and diversify the current TB vaccine and biomarker pipeline while at the same time applying portfolio management using gating and priority setting criteria to select as early as possible the most promising TB vaccine candidates, and accelerate their development. TBVAC2020 proposes to achieve this by combining creative bottom-up approaches for vaccine discovery (WP1), new preclinical models addressing clinical challenges (WP2) and identification and characterisation of correlates of protection (WP5) with a directive top-down portfolio management approach aiming to select the most promising TB vaccine candidates by their comparative evaluation using objective gating and priority setting criteria (WP6) and by supporting direct, head-to head or comparative preclinical and early clinical evaluation (WP3, WP4). This approach will both innovate and diversify the existing TB vaccine and biomarker pipeline as well as accelerate development of most promising TB vaccine candidates through early development stages. The proposed approach and involvement of many internationally leading groups in the TB vaccine and biomarker area in TBVAC2020 fully aligns with the Global TB Vaccine Partnerships (GTBVP).
Hirao L.A.,University of Pennsylvania |
Hokey D.A.,Aeras Global TB Vaccine Foundation |
Morrow M.P.,University of Pennsylvania |
Morrow M.P.,Inovio Pharmaceuticals, Inc. |
And 2 more authors.
PLoS ONE | Year: 2011
Costimulatory molecules play a central role in the development of cellular immunity. Understanding how costimulatory pathways can be directed to positively influence the immune response may be critical for the generation of an effective HIV vaccine. Here, we evaluated the ability of intravenous administration of a blocking monoclonal antibody (mAb) directed against the negative costimulatory molecule CTLA-4, and an agonist mAb directed against the positive costimulatory molecule 4-1BB, either alone or in combination, to augment intramuscular SIV DNA immunizations. We then tested the ability these of these responses to impact a high-dose SIVmac251 challenge. Following immunization, the groups infused with the anti-4-1BB mAb exhibited enhanced IFN-γ responses compared to the DNA vaccine only group. Interestingly, although CTLA-4 blockade alone did not enhance IFN-γ responses it did increase the proliferative capacity of the CD4 + and CD8 + T cells. The combination of both mAbs enhanced the magnitude of the polyfunctional CD8 + T cell response. Following challenge, the group that received both mAbs exhibited a significant, ~2.0 log, decrease in plasma viral load compared to the naïve group the included complete suppression of viral load in some animals. Furthermore, the use of the CTLA-4 blocking antibody resulted in significantly higher viral loads during chronic infection compared to animals that received the 4-1BB mAb, likely due to the higher CD4 + T cell proliferative responses which were driven by this adjuvant following immunization. These novel studies show that these adjuvants induce differential modulation of immune responses, which have dramatically different consequences for control of SIV replication, suggesting important implications for HIV vaccine development. © 2011 Hirao et al.
Jin T.H.,Aeras Global TB Vaccine Foundation |
Tsao E.,Aeras Global TB Vaccine Foundation |
Goudsmit J.,Crucell |
Dheenadhayalan V.,Aeras Global TB Vaccine Foundation |
Sadoff J.,Aeras Global TB Vaccine Foundation
Vaccine | Year: 2010
A powder vaccine intended for aerosol delivery was formulated by spray drying the Ad35-vectored tuberculosis (TB) AERAS-402 vaccine with mannitol-based stabilizers. Thermodynamic properties, water absorption, particle size distribution and morphology of the powders were evaluated. Virus survival during spray drying and storage was determined by medium Tissue Culture Infectious Dose (TCID50). A mannitol-based powder (mannitol-cyclodextrin-trehalose-dextran, MCTD) had a narrow size distribution with a median volume diameter around 3.2-3.5 μm (suitable for pulmonary vaccination of humans) and good aerosolization characteristics. The spray dry powders generated from mannitol-based formulations were hydrophobic, which benefits virus survival during both production and storage at 4 °C, 25 °C and 37 °C as compared to the hygroscopic formulations (trehalose, sucrose, dextran, PVP, leucine). In conclusion, this study demonstrates that it is possible to produce in a one-step spray drying process a stable dry powder formulation of a TB vaccine suitable for mass vaccination. © 2010 Elsevier Ltd. All rights reserved.
Delogu G.,Catholic University of the Sacred Heart |
Fadda G.,Catholic University of the Sacred Heart |
Brennan M.J.,Aeras Global TB Vaccine Foundation
Protein and Peptide Letters | Year: 2012
Among the few well characterized virulence factors of Mycobacterium tuberculosis (Mtb) is the heparinbinding hemagglutinin (HBHA). HBHA is a 21-kDa protein that localizes to the mycobacterial surface where it can interact with host components. Interaction with epithelial cells and components of the extracellular matrix is mediated by the methylated lysine-rich C-terminal domain of the protein. The N-terminal end of HBHA contains a coiled coil motif which is involved in protein oligomerization and bacterial-bacterial aggregation. In this report, we will focus our attention on what is known about the structure of the HBHA protein and the protein function and role in TB pathogenesis. © 2012 Bentham Science Publishers.
Beresford B.,Aeras Global TB Vaccine Foundation |
Sadoff J.C.,Aeras Global TB Vaccine Foundation
Clinical Infectious Diseases | Year: 2010
Current tuberculosis (TB)-control methods, which do not include an adequate vaccine, do not effectively block transmission of TB. Modeling studies show that mass vaccination campaigns using new vaccines could prevent 85.9 million new cases and 14.5 million deaths from 2015 through 2050 in southern Asia alone. After a dearth of many years, the development pipeline now includes 7 vaccine candidates that are being tested in humans. Two nonreplicating viral vectored vaccines have very recently entered the first phase Hb efficacy trial in infants (the first such trial in 80 years) and in human immunodeficiency virus-infected adults. Science is moving forward, but the scientific advancements need to be accompanied by political mobilization to ensure that the resources are available to develop, manufacture, and distribute the new vaccines and, thus, save millions of lives. © 2010 by the Infectious Diseases Society of America. All rights reserved.
Hawkridge T.,Aeras Global TB Vaccine Foundation |
Mahomed H.,Aeras Global TB Vaccine Foundation |
Mahomed H.,University of Cape Town
Paediatric Respiratory Reviews | Year: 2011
Tuberculosis in infants and young children remains an all too common cause of morbidity and mortality in high burden countries, despite the fact that the majority of these children receive vaccination with BCG in infancy. BCG confers incomplete and variable protection against pulmonary tuberculosis [PTB] and is unsafe in HIV positive persons. Newer TB vaccines, which, it is hoped, will either replace or complement BCG are being developed and a number of these have reached the stage of clinical trials, with two booster vaccines going into Phase IIB trials in 2009. Prospects for at least one new licensed TB vaccine within the next 5-10 years appear reasonable. This article explores some of the issues around the development of new vaccines against TB and details the leading candidates. © 2010 Elsevier Ltd.
Hokey D.A.,Aeras Global TB Vaccine Foundation |
Misra A.,CSIR - Central Electrochemical Research Institute
Tuberculosis | Year: 2011
Pulmonary delivery of vaccines against airborne infection is being investigated worldwide, but there is limited effort directed at developing inhaled vaccines for tuberculosis (TB). This review addresses some of the challenges confronting vaccine development for TB and attempts to link these challenges to the promises of mucosal immunity offered by pulmonary delivery. There are several approaches working toward this goal including subunit vaccines, recombinant strains, a novel vaccine strain Mycobacterium w, and DNA vaccine approaches. While it is clear that lung-resident adaptive immunity is an attainable goal, vaccine platforms must ensure that damage to the lung is limited during both vaccination and when memory cells respond to pathogenic infection. © 2010 Elsevier Ltd. All rights reserved.
Aeras Global Tb Vaccine Foundation, French Institute of Health and Medical Research | Date: 2012-04-16
Recombinant Mycobacteria (rMyc) which contain sequences encoding a heparin-binding hemagglutinin (HBHA) fusion protein are provided, as are methods of making and using the rMyc and the fusion protein. The fusion protein includes an amino terminal mycobacterial antigen Ag85B leader peptide and transcription of the fusion protein is driven by an Ag85B promoter sequence. The recombinant fusion protein is produced in abundance by the rMyc, is post-translationally methylated, and is highly antigenic.
Aeras Global Tb Vaccine Foundation | Date: 2014-06-24
The present disclosure provides fusion proteins comprising Mycobacterium tuberculosis (Mtb) antigens, nucleic acid molecules encoding the same, vectors comprising nucleic acid molecules, compositions comprising the same, and methods of eliciting an immune response against tuberculosis.
Aeras Global Tb Vaccine Foundation | Date: 2013-04-08
Bacterial delivery systems with improved transgene expression are provided. The recombinant bacterial delivery systems deliver transgenes of interest and suppressors of the eukaryotic Type I interferon response to eukaryotic cells. Suppression of the eukaryotic Type I interferon response allows improved expression of the encoded transgene.