A universal T cell vaccine for HIV-1

Lead Research Organisation: University of Oxford
Department Name: Central Admin - Research Services

Abstract

HIV infection and AIDS continues to spread in a virtually uncontrolled manner. The best and possibly only hope to change this alarming situation is a safe, effective, accessible protective vaccine. Arguably the biggest challenge in developing such a vaccine is enormous HIV variability, which dwarfs that of almost any other infection. However, all parts of the virus cannot easily change. To remain alive, HIV has to keep some smaller regions of its proteins more or less constant. We have taken an advantage of this and constructed a candidate vaccine designed specifically to overcome HIV variability by focusing the body defences on the conserved regions of the virus, i.e. the Achilles heel of HIV. Here, we are proposing to build on and extend our ongoing vaccine development effort and, if successful, assemble a strong case for further evaluation of this vaccination strategy in larger scale and expensive field efficacy studies.

Technical Summary

The best solution to the HIV/AIDS epidemic is development of an effective prophylactic vaccine. T cell stimulating vaccines offer a realistic alternative, or supplement to, antibody inducing vaccines. The latter are proving extremely difficult to generate and T cell stimulating vaccines, while not preventing infection, do ameliorate disease in monkey/SIV models. However, virus variability is a major problem resulting in poor recognition of infecting virus and easy escape of virus from early T cell control. These issues could be avoided by focusing vaccine-induced T cell responses on conserved regions of HIV-1. While most patients with chronic HIV-1 infection do make some T cell responses to conserved regions, these responses are usually weak (subdominant) and, like broadly neutralizing antibody responses, develop too late in the infection to provide real benefit. We have constructed immunogen HIVconsv, which is derived from the 14 least variable HIV-1 segments and contains over 200 epitopes, and have shown that it stimulates strong T cell responses in mice and in rhesus macaques. Phase I clinical trials in Oxford evaluating safety and immunogenicity of three HIVconsv vaccines delivered as plasmid DNA, recombinant MVA and recombinant chimpanzee adenovirus have started.
Here, we shall further refine the vaccine design to improve the prototype immunogen, vaccine vectors and their formulation. We shall test different vaccination regimens to maximize T cell induction and assess surrogate efficacy in inbred and outbred mice. We shall make a second ?mosaic? immunogen complementing HIVconsv, which will improve perfect matching of amino acids to HIV-1 variants from clades A,B,C and D from 72% to 90%. We shall study in depth vaccine-induced responses in humans, looking at how well the known conserved (but often subdominant in HIV-1 infection) epitopes are presented by antigen-presenting cells exposed to these constructs. We shall examine how efficiently the HIVconsv-specific T cells recognize and kill HIV-1-infected cells. We shall employ state-of-the-art proteomics (tandem MS/nanoflow RPLC) to obtain a comprehensive picture of conserved region peptide processing and presentation on the cell surface, and comparing epitope presentation from the HIVconsv vaccines and HIV-1. This will indicate whether the HIVconsv needs further optimization.
Results generated from this programme together with our complementing, separately funded components (non-human primate and human trials) will be key in assessing the suitability of conserved region T cell vaccines for efficacy trials in high-risk human cohort(s), either alone or with an antibody-based vaccine.

Publications

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publication icon
Abdul-Jawad S (2016) Increased Valency of Conserved-mosaic Vaccines Enhances the Breadth and Depth of Epitope Recognition. in Molecular therapy : the journal of the American Society of Gene Therapy

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Borthwick N (2014) Vaccine-elicited human T cells recognizing conserved protein regions inhibit HIV-1. in Molecular therapy : the journal of the American Society of Gene Therapy

 
Description CHAVI-ID (Duke)
Amount $100,000 (USD)
Organisation National Institutes of Health (NIH) 
Sector Public
Country United States
Start 01/2016 
End 06/2017
 
Description EAVI2020
Amount € 22,900,000 (EUR)
Organisation European Commission 
Sector Public
Country European Union (EU)
Start 11/2015 
End 10/2021
 
Description EDCTP Strategic Primer
Amount € 800,000 (EUR)
Funding ID SP.2011.41304.002 
Organisation Sixth Framework Programme (FP6) 
Department European and Developing Countries Clinical Trials Partnership
Sector Public
Country European Union (EU)
Start 01/2012 
End 01/2015
 
Description FP7
Amount € 7,000,000 (EUR)
Funding ID 305632 
Organisation European Commission 
Sector Public
Country European Union (EU)
Start 10/2013 
End 09/2017
 
Description GMP manufacture
Amount $2,200,000 (USD)
Funding ID SOW4 and SOW5 
Organisation International AIDS Vaccine Initiative (IAVI) 
Sector Charity/Non Profit
Country Global
Start 01/2015 
End 12/2016
 
Description ISSF Wellcome Trust
Amount £50,000 (GBP)
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 07/2012 
End 07/2014
 
Description MRC DCS
Amount £1,031,751 (GBP)
Funding ID MR/J008605/1 
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 11/2012 
End 09/2015
 
Description MRC RIVER DCS
Amount £2,000,000 (GBP)
Funding ID MR/L00528X/1 
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 10/2014 
End 09/2017
 
Title 2nd generation HIVconsv vaccines 
Description 2nd generation improved HIVconsv vaccines Improved immunogens with increased global coverage of HIV variants 
Type Of Material Technology assay or reagent 
Year Produced 2013 
Provided To Others? Yes  
Impact Under construction 
 
Title Elution and analysis of HLA class I-associated peptidomes 
Description Methodology for identifying HLA class i-associated peptides derived from intracellular pathogens 
Type Of Material Technology assay or reagent 
Provided To Others? No  
Impact Publications in preparation or submitted and lots of interest from pathogens other than HIV 
 
Title HIV vaccines inducing antibodies 
Description Vaccines aiming at induction of broadly neutralizing anti-HIV antibody Genes for modified BG505 Env immunogens were inserted into DNA, MVA and ChAdV 
Type Of Material Technology assay or reagent 
Provided To Others? No  
Impact Experiments ongoing 
 
Title Vaccine focus on conserved regions of microbes 
Description The biggest roadblock for many vaccines is the pathogens' variability. This is best tackled by focusing both antibodies and T cells on the functionally most conserved regions of proteins common to many variants including escape mutants. For vectored vaccines, these 'universal' subunit immunogens are most efficiently delivered using heterologous prime-boost regimens, which can be further optimized by adjuvantation and route of delivery. 
Type Of Material Model of mechanisms or symptoms - human 
Year Produced 2011 
Provided To Others? Yes  
Impact Selecting for vaccine immunogens conserved regions of microbes common to many variants - HIV, HCV, Flu, Dengue 
 
Description A Phase I/II Randomized, Placebo-Controlled Trial of Therapeutic Vaccination with Conserved HIV-1 Immunogens in Adults Initiated on Suppressive Antiretroviral Therapy during Acute HIV-1 Infection 
Organisation University of Pittsburgh
Country United States 
Sector Academic/University 
PI Contribution Provision of four GMP vaccines for a clinical trial in HIV-positive adults
Collaborator Contribution Run a clinical trials and outcome assays
Impact none as yet
Start Year 2017
 
Description Adjuvantation by PIV5 DI particles 
Organisation University of St Andrews
Country United Kingdom 
Sector Academic/University 
PI Contribution Adjuvantation by PIV5 DI particles will be evaluated in mice. We shall use our candidate HIVconsv vaccines and carry out the experiments.
Collaborator Contribution Provision of PIV5 DI particles
Impact Multidisciplinary, we shall aim to publish our results.
Start Year 2012
 
Description Analysis of T cell responses in antiretroviral treatment-naive patients 
Organisation University of Kumamoto
Country Japan 
Sector Academic/University 
PI Contribution Identification of conserved regions and provision of corresponding peptides Identification and mapping of conserved region vaccine elicited epitopes
Collaborator Contribution Measurements of T cell responses and HIV viral load in treatment-naive patients and correlation of magnitude and breadth of responses with viral load and CD4 cell counts Determination of HLA-restriction of mapped epitopes
Impact Multidisciplinary, publications out and in preparation
Start Year 2013
 
Description Antibody Vaccine Development 
Organisation Cornell University
Department Weill Cornell Medicine
Country United States 
Sector Academic/University 
PI Contribution Construction of new vaccines Pre-clinical immunogenicity Optimizing co-delivery of Ab and T cell vaccines
Collaborator Contribution Immunogen BG505 SOSIP Structural characterization of expressed proteins
Impact Vaccines under construction
Start Year 2013
 
Description Assessment of tHIVconsvX-specific responses in HIV-positive patients 
Organisation Imperial College London
Country United Kingdom 
Sector Academic/University 
PI Contribution Design and provision of tHIVconsvX peptides
Collaborator Contribution Testing of peptides in HIV-1-positive patients
Impact In progress
Start Year 2014
 
Description Clinical evaluation of ChAdV63.HIVconsv 
Organisation GlaxoSmithKline (GSK)
Country Global 
Sector Private 
PI Contribution GSK acquired Okairos, the developer of the ChAdV-63-based vector platform. We are testing the ChAdV63.HIVconsv in four clinical trials: RIVER, PEACHI 04, HIV-CORE 003 and BCN 01.
Collaborator Contribution The GSK partner added a very slow and cumbersome process of approving of the jointly owned candidate vaccine for use in clinical trials. GSK is not interested in an early stage development of HIV vaccines.
Impact In process.
Start Year 2013
 
Description Clinical trial HIV-CORE 001, 002, 003, 004 and RIVER, BCN01, BCN02 and PEACHI-04 volunteers 
Organisation IrsiCaixa Institute for AIDS Research
Country Spain 
Sector Public 
PI Contribution Providing GMP vaccines, expertise and input on trial design and immunological analysis
Collaborator Contribution Lucy Dorrell will provide a cohort of HIV-1-infected patients and carry out clinical trial evaluating safety and immunogenicity the MVA.HIVconsv vaccine.
Impact Safety and immunogenicity data on the MVA.HIVconsv vaccine.
Start Year 2010
 
Description Clinical trial HIV-CORE 001, 002, 003, 004 and RIVER, BCN01, BCN02 and PEACHI-04 volunteers 
Organisation University College London
Country United Kingdom 
Sector Academic/University 
PI Contribution Providing GMP vaccines, expertise and input on trial design and immunological analysis
Collaborator Contribution Lucy Dorrell will provide a cohort of HIV-1-infected patients and carry out clinical trial evaluating safety and immunogenicity the MVA.HIVconsv vaccine.
Impact Safety and immunogenicity data on the MVA.HIVconsv vaccine.
Start Year 2010
 
Description Comparison of Dendri/c Cell-­Based Therapeu/c Vaccine Strategies for HIV Func/onal Cure 
Organisation University of Pittsburgh
Country United States 
Sector Academic/University 
PI Contribution Design of peptides used in the clinical trials, trial design and outcome analysis
Collaborator Contribution Run a clinical trial and the outcome assays
Impact no output yet
Start Year 2017
 
Description Construction and preclinical evaluation of ChAdOx1.HIVACAT-T vaccines 
Organisation HIVACAT Program IrsiCaixa Institute for AIDS Research
Country Spain 
Sector Multiple 
PI Contribution Design of a synthetic genes and construction of candidate HIV vaccine ChAdOx1.HIVACAT-T
Collaborator Contribution Design of the immunogen and pre-clinical testing
Impact In progress
Start Year 2013
 
Description Construction and testing of Retrovirus-vectored tHIVconsvX vaccines 
Organisation Immune Design
Country United States 
Sector Private 
PI Contribution Provision of 2 tHIVconsvX genes and preclinical testing of candidate vaccines.
Collaborator Contribution Construction of two candidate vaccines.
Impact In progress
Start Year 2013
 
Description Construction of CMV-vectored vaccines and pre-clinical studies 
Organisation Oregon Health and Science University
Country United States 
Sector Academic/University 
PI Contribution Design and provision of two synthetic genes coding for tSIVconsv239 and tSIVconsvE660 Construction of chimp Adenovirus and MAV vectored vaccines carrying the tSIVconsv genes
Collaborator Contribution Construction of CMV.tSIVconsv239 and CMV.tSIVconsvE660 and immunogenicty study in primates
Impact In progress
Start Year 2013
 
Description Construction of HAdV-4-vectored tHIVconsvX vaccines 
Organisation PaxVax, Inc.
Country United States 
Sector Private 
PI Contribution Provision of two tHIVconsvX genes and pre-clinical evaluation
Collaborator Contribution Construction of candidate vaccines
Impact In progress
Start Year 2013
 
Description Construction of ID-lentiviral vectors for delivery of conserved mosaic vaccines 
Organisation Immune Design
Country United States 
Sector Private 
PI Contribution We provided designed and provided genes coding forHIV-derived conserved mosaic immunogens and tested the ImmuneDesign-generated vaccines in mice
Collaborator Contribution Immune Design provided lentiviral vectors and inserted our conserved mosaic immunogens gene into them to construct two candidate vaccines
Impact Manuscript ready for submission
Start Year 2014
 
Description Construction of MVA.HIVACAT-T for pre-clinical and clinical testing 
Organisation HIVACAT Program IrsiCaixa Institute for AIDS Research
Country Spain 
Sector Multiple 
PI Contribution Construction of candidate HIV vaccine MVA.HIVACAT-T carrying a IRSICAIXA-designed T cell immunogen Advice on GMP manufacture
Collaborator Contribution Design of HIVACAT-T immunogen, preclinical testing in mice and monkeys. GMP manufacture
Impact Publication submitted
Start Year 2012
 
Description Construction of rBCG for delivery of conserved mosaic vaccines 
Organisation Albert Einstein College of Medicine
Country United States 
Sector Academic/University 
PI Contribution We provide gene for conserved mosaic HIV vaccine and shall conduct pre-clinical immunogenicity studies in mice
Collaborator Contribution Construct rBCG and provide sufficient stocks for preclinical studies
Impact Work in progress
Start Year 2014
 
Description Design of 2nd generation tHIVconsvX vaccines 
Organisation Los Alamos National Laboratory
Country United States 
Sector Public 
PI Contribution Computer design of the 2nd generation conserved T cell immunogens tHIVconsvX
Collaborator Contribution Designed the 2 mosaics used and helped to select the conserved regions oh the HIV -1 proteome
Impact 2nd generation vaccine - so far pre-clinical grade constructed A joint Patent between UOXF/ISIS and LANL
Start Year 2013
 
Description Determination of binding affinities of peptides for HLA 
Organisation University of Southampton
Country United Kingdom 
Sector Academic/University 
PI Contribution Peptide identification and provision
Collaborator Contribution HLA affinity assay
Impact Manuscript in preparation
Start Year 2014
 
Description Development of RhCMV-vectored conserved region vaccines 
Organisation Oregon Health and Science University
Country United States 
Sector Academic/University 
PI Contribution We provided SIV equivalents of our human conserved region mosaic immunogen (SIVconsv239 and SIVconsvE660) genes and vaccines expressing the same immunogens from ChAdOx1 and MVA
Collaborator Contribution Louis PIcker and Scott Hansen constructed RhCMV-vectored vaccines expressing SIVconsv239 and SIVconsvE660, immunized 16 rhesus macaques and will challenge them with SIVmac239
Impact Work in progress
Start Year 2014
 
Description Development of a conserved mosaic protein as an immunogen 
Organisation Los Alamos National Laboratory
Country United States 
Sector Public 
PI Contribution We describe what immunogen we would like to design and LANL used their computational power to design this immunogen. We then construct it and develop it
Collaborator Contribution Providing an expertise in designing a vaccine immunogen
Impact Early days
Start Year 2010
 
Description European AIDS Vaccine Initiative 2020 (EAVI2020) 
Organisation European AIDS Vaccine Initiative 2020 (EAVI2020)
Country European Union (EU) 
Sector Charity/Non Profit 
PI Contribution We shall provided preclinical and Experimental Medicine research, our conserved mosaic HIV vaccines and our expertise
Collaborator Contribution Our partners will provided preclinical and Experimental Medicine research, their candidate HIV vaccines and their expertise
Impact It is work in progress www.eavi2020.eu Twitter www.twitter.com/eavi2020 Like us on Facebook: www.facebook.com/eavi2020 LinkedIn: www.linkedin.com/company/eavi2020 ResearchGate: https://www.researchgate.net/profile/Eavi_2020
Start Year 2015
 
Description GMP manufacture of ChAdOx1.tHIVconsv5 and ChAdOx1.tHIVconsv6 
Organisation International AIDS Vaccine Initiative (IAVI)
Country Global 
Sector Charity/Non Profit 
PI Contribution Manufacture of two experimental vaccines for clinical use
Collaborator Contribution CBF will manufacture the vaccine IAVI provided the funds for one vaccine
Impact Clinical batches of two vaccines will be produced
Start Year 2015
 
Description GMP manufacture of ChAdOx1.tHIVconsv5 and ChAdOx1.tHIVconsv6 
Organisation University of Oxford
Department The Clinical Biomanufacturing Facility
Country United Kingdom 
Sector Academic/University 
PI Contribution Manufacture of two experimental vaccines for clinical use
Collaborator Contribution CBF will manufacture the vaccine IAVI provided the funds for one vaccine
Impact Clinical batches of two vaccines will be produced
Start Year 2015
 
Description GMP manufacture of MVA.tHIVconsv3 and MVA.tHIVconsv4 
Organisation IDT Biologika GmbH
Country Germany 
Sector Private 
PI Contribution Manufacture of two vaccines for clinical trial use
Collaborator Contribution IDT is the manufacturing house IAVI paid for one rMVA
Impact When completed, clinical lots of two experimental vaccines
Start Year 2015
 
Description GMP manufacture of MVA.tHIVconsv3 and MVA.tHIVconsv4 
Organisation International AIDS Vaccine Initiative (IAVI)
Country Global 
Sector Charity/Non Profit 
PI Contribution Manufacture of two vaccines for clinical trial use
Collaborator Contribution IDT is the manufacturing house IAVI paid for one rMVA
Impact When completed, clinical lots of two experimental vaccines
Start Year 2015
 
Description HIV inhibition assays 
Organisation International AIDS Vaccine Initiative (IAVI)
Department Human Immunology Laboratory, ICL
Country United States 
Sector Charity/Non Profit 
PI Contribution We provide samples from clinical trial, a visiting DPhil student and contribute to the cost of the virus inhibition assay (VIA)
Collaborator Contribution International AIDS Vaccine Initiative provide the expertise in VIA, welcome our student and provided HIV virus stock of various clades
Impact Assays are in progress.
Start Year 2012
 
Description HIVconsv vaccine development 
Organisation International AIDS Vaccine Initiative (IAVI)
Country Global 
Sector Charity/Non Profit 
PI Contribution Developed vaccine strategy, got funding from EDCTP
Collaborator Contribution Contribution towards running of trial HIV-CORE 004 1-year post-doc plus expenses
Impact Clinical trial, optimizing vaccine delivery pre-clinically
Start Year 2012
 
Description HLA associated peptidome characterization 
Organisation University of Oxford
Department Radcliffe Department of Medicine
Country United Kingdom 
Sector Academic/University 
PI Contribution Methodology for eluting and identifying HLA-associated peptidome
Collaborator Contribution expertise in rheumatilogy
Impact Multi-disciplinary collaboration resulting in a publication
Start Year 2012
 
Description Impact of mosaic design on T cell response cloncality 
Organisation Cardiff University
Country United Kingdom 
Sector Academic/University 
PI Contribution Vaccine construction, immunisation of mice and T cell assays, tetramer design
Collaborator Contribution Tetramer sorting of immune mouse splenocytes and T cell receptor analysis
Impact In progress
Start Year 2013
 
Description Impact of mosaic design on T cell response cloncality 
Organisation Los Alamos National Laboratory
Country United States 
Sector Public 
PI Contribution Vaccine construction, immunisation of mice and T cell assays, tetramer design
Collaborator Contribution Tetramer sorting of immune mouse splenocytes and T cell receptor analysis
Impact In progress
Start Year 2013
 
Description Impact of mosaic design on T cell response cloncality 
Organisation National Institutes of Health (NIH)
Country United States 
Sector Public 
PI Contribution Vaccine construction, immunisation of mice and T cell assays, tetramer design
Collaborator Contribution Tetramer sorting of immune mouse splenocytes and T cell receptor analysis
Impact In progress
Start Year 2013
 
Description Importance of vectors for induction of broadly neutralising anti-HIV antibodies 
Organisation Duke University
Department Duke Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID)
Country United States 
Sector Academic/University 
PI Contribution We shall determine the importance of virus vector delivery in heterologous prime-boost regimens for induction of HIV broadly neutralizing antibodies.
Collaborator Contribution CHAVI-ID/Barton Haynes (Duke University) provided HIV Envelope genes from sequential HIV isolates with the idea to guide the maturation of antibody affinity.
Impact In progress
Start Year 2016
 
Description Induction of HIV neutralizing antibodies 
Organisation Cornell University
Department Weill Cornell Medicine
Country United States 
Sector Academic/University 
PI Contribution We are developing heterologous prime-boost immunisation regimen delivering a highly promising HIV Env BG505 uncleaved or as SOSIP for induction of HIV neutralising antibodies. Also we are developing regimens for efficient induction of T cell and B cell responses in parallel.
Collaborator Contribution WCMC - provision or trimeric gp140 BG505 SOSIP protein immunogen IAVI - proviion of gp120 HBG505 unlceaved immunogen Sir Willima Dunn Schol of Pathology - quality control and research assays for characterisation of vector-expressed Ev immunogen Meditox - rabbit immunization study
Impact Studies with BG505 uncleaved - Publication Studies with BG505 SOSIP - In progress
Start Year 2014
 
Description Induction of HIV neutralizing antibodies 
Organisation International AIDS Vaccine Initiative (IAVI)
Country Global 
Sector Charity/Non Profit 
PI Contribution We are developing heterologous prime-boost immunisation regimen delivering a highly promising HIV Env BG505 uncleaved or as SOSIP for induction of HIV neutralising antibodies. Also we are developing regimens for efficient induction of T cell and B cell responses in parallel.
Collaborator Contribution WCMC - provision or trimeric gp140 BG505 SOSIP protein immunogen IAVI - proviion of gp120 HBG505 unlceaved immunogen Sir Willima Dunn Schol of Pathology - quality control and research assays for characterisation of vector-expressed Ev immunogen Meditox - rabbit immunization study
Impact Studies with BG505 uncleaved - Publication Studies with BG505 SOSIP - In progress
Start Year 2014
 
Description Induction of HIV neutralizing antibodies 
Organisation MediTox s.r.o.
Country Czech Republic 
Sector Academic/University 
PI Contribution We are developing heterologous prime-boost immunisation regimen delivering a highly promising HIV Env BG505 uncleaved or as SOSIP for induction of HIV neutralising antibodies. Also we are developing regimens for efficient induction of T cell and B cell responses in parallel.
Collaborator Contribution WCMC - provision or trimeric gp140 BG505 SOSIP protein immunogen IAVI - proviion of gp120 HBG505 unlceaved immunogen Sir Willima Dunn Schol of Pathology - quality control and research assays for characterisation of vector-expressed Ev immunogen Meditox - rabbit immunization study
Impact Studies with BG505 uncleaved - Publication Studies with BG505 SOSIP - In progress
Start Year 2014
 
Description Induction of HIV neutralizing antibodies 
Organisation University of Oxford
Department Sir William Dunn School of Pathology
Country United Kingdom 
Sector Academic/University 
PI Contribution We are developing heterologous prime-boost immunisation regimen delivering a highly promising HIV Env BG505 uncleaved or as SOSIP for induction of HIV neutralising antibodies. Also we are developing regimens for efficient induction of T cell and B cell responses in parallel.
Collaborator Contribution WCMC - provision or trimeric gp140 BG505 SOSIP protein immunogen IAVI - proviion of gp120 HBG505 unlceaved immunogen Sir Willima Dunn Schol of Pathology - quality control and research assays for characterisation of vector-expressed Ev immunogen Meditox - rabbit immunization study
Impact Studies with BG505 uncleaved - Publication Studies with BG505 SOSIP - In progress
Start Year 2014
 
Description LC-MS/MS 
Organisation University of Oxford
Department Central Proteomic Facility
Country United Kingdom 
Sector Academic/University 
PI Contribution The aim is to analyze the HLA-associated peptidome on HIV or HIVconsv expressing cells. Post-doctoral scientist and some key reagents.
Collaborator Contribution Know-how and equipment.
Impact Multidisciplinary, ongoing, publications anticipated.
Start Year 2011
 
Description Phase I therapeutic testing of viral-vectored vaccines that shift CD8+ T-cell immunodominance to conserved regions of HIV-1 
Organisation University of North Carolina at Chapel Hill
Department Department of Microbiology and Immunology
Country United States 
Sector Academic/University 
PI Contribution Provision of two GMP vaccines, input into trial design and evaluation
Collaborator Contribution Running a vaccine trial in HIV-positive individuals
Impact none yet
Start Year 2017
 
Description Sample evaluation at HVTN 
Organisation HIV Vaccine Trials Network, USA
Country United States 
Sector Charity/Non Profit 
PI Contribution We have provided samples from clinical trial HIV-CORE002 and peptides.
Collaborator Contribution Know-how, evaluation of samples in standardized, reference assays.
Impact Comparative data with other vaccine strategies.
Start Year 2012
 
Description Sample evaluation in HIL reference laboratory 
Organisation International AIDS Vaccine Initiative (IAVI)
Department Human Immunology Laboratory, ICL
Country United States 
Sector Charity/Non Profit 
PI Contribution Frozen PBMC samples from clinical trial
Collaborator Contribution IFN-y ELISPOT assays comparative with other HIV vaccine candidates tested by IAVI and others
Impact The results will likely be part of publication describing immunogenicity of the HIVconsv vaccines tested in HIV-CORE002. Comparative data with other vaccine strategies.
Start Year 2012
 
Description Vacc2020 Development of scalable manufacturing processing form ChAdV and MVA 
Organisation IDT Biologika GmbH
Country Germany 
Sector Private 
PI Contribution Application under review
Collaborator Contribution Application under review
Impact Application under review
Start Year 2014
 
Description Vaccine Manufacturing project 
Organisation Advent S.r.l
Country Italy 
Sector Private 
PI Contribution Provision of starting material and guidance throughout the manufacturing process
Collaborator Contribution Pre-GMP development
Impact non yet
Start Year 2016
 
Description Vaccine manufacture 
Organisation IDT Biologika GmbH
Country Germany 
Sector Private 
PI Contribution Provision of starting materials for two vaccines
Collaborator Contribution Pre-GMP development, manufacture and fill finish of two vaccines
Impact Two GMP vaccines
Start Year 2016
 
Title Mosaic conserved region HIV immunogenic polypeptides 
Description Disclosed herein are mosaic conserved region HIV polypeptides that can elicit an immune response to HIV (such as cytotoxic T cell (CTL), helper T cell, and/or hum oral responses). Also disclosed herein are immunogenic polypeptides including one or more of the mosaic conserved region polypeptides. In some examples, two or more of the mosaic conserved region polypeptides are included in a fusion (or chimeric) immunogenic polypeptide. In some 30 embodiments, the disclosed immunogenic polypeptides are included in an immunogenic composition, such as a polyvalent immunogenic composition. Also disclosed herein are methods for treating or inhibiting HIV in a subject including administering one or more (such as two or more) of the disclosed immunogenic polypeptides orcompositions to a subject infected with HIV or at risk of HIV infection. Also disclosed are methods of inducing an immune response to HIV in a subject by administering to the subject at least one (such as two or more) of the immunogenic polypeptides or a nucleic acid encoding at least one of the immunogenic polypeptides disclosed herein. 
IP Reference PCT/US2014/058422 and UK Application No 61/884705 
Protection Patent application published
Year Protection Granted 2014
Licensed No
Impact N/A
 
Title BCN 01 
Description The first immunogenicity evaluation of ChAdV63.HIVconsv prime-MVA.HIVconsv boost vaccine regimen delivering conserved regions of the HIV-1 proteome in HIV-1-infected individuals early on HAART 
Type Therapeutic Intervention - Vaccines
Current Stage Of Development Early clinical assessment
Year Development Stage Completed 2013
Development Status Under active development/distribution
Clinical Trial? Yes
Impact The fist therapeutic use of this vaccine regimen in HIV-infected individuals 
 
Title BCN 02 - ROMI 
Description http://www.croiconference.org/sessions/viral-control-induced-hivconsv-vaccines-romidepsin-early-treated-individuals 
Type Therapeutic Intervention - Vaccines
Current Stage Of Development Initial development
Year Development Stage Completed 2017
Development Status Under active development/distribution
Clinical Trial? Yes
Impact Early times 
URL http://www.croiconference.org/sessions/viral-control-induced-hivconsv-vaccines-romidepsin-early-trea...
 
Title HIV-CORE 001 
Description The first use of conserved region vaccine MVA.HIVconsv in HIV-infected individuals in UK Primarily supported by a MRC award to Dr Lucy Dorrell 
Type Therapeutic Intervention - Vaccines
Current Stage Of Development Early clinical assessment
Year Development Stage Completed 2013
Development Status Actively seeking support
Clinical Trial? Yes
Impact The first use of conserved region vaccine in man 
 
Title HIV-CORE 002 
Description HIVconsv is a universal T cell immunogen focusing T cells responses on the conserved, i.e. common regions of the HIV-1 proteome. HIVconsv was delivered by DNA, modified vaccinia virua Ankara (MVA) and chimpanzee adenovirus serotype 63 (ChAdV-63) to healthy uninfected individual in UK. It is prophylactic, not therapeutic vaccine. 
Type Therapeutic Intervention - Vaccines
Current Stage Of Development Early clinical assessment
Year Development Stage Completed 2012
Development Status Actively seeking support
Clinical Trial? Yes
Impact The first use of HIV vaccine based on conserved regions of the HIV-1 proteome to healthy individuals, the first use of ChAdV-63 for HIV vaccines, the first use of ChAdV-63 prime-MVA boost and DNA-ChAdV-63-MVA regimens for HIV in man 
 
Title HIV-CORE 003 
Description The first assessment of enhancement of DNA vaccination by serum amyloid component B depletion by CPHPC iv infusion in man Primarily supported by an MRC award to Professor Sir Mark Pepys 
Type Therapeutic Intervention - Vaccines
Current Stage Of Development Early clinical assessment
Year Development Stage Completed 2013
Development Status Under active development/distribution
Clinical Trial? Yes
Impact Proof of concept trial 
 
Title HIV-CORE 004 
Description The first evaluation of the conserved region vaccines delivered by DNA (electroporated), MVA and HAdV-35 in healthy HIV-uninfected adults in Nairobi, Kenya Prophylactic, not therapeutic vaccine Trial is in not completed Mainly supported by EDCTP award 
Type Therapeutic Intervention - Vaccines
Current Stage Of Development Refinement. Clinical
Year Development Stage Completed 2013
Development Status Under active development/distribution
Clinical Trial? Yes
UKCRN/ISCTN Identifier Ref no. PPB/ECCT/13/07/01/2013/(100) (Kenya regulator)
Impact The first test of these vaccine in Africa 
 
Title PEACHI 04 
Description We shall test novel potent T cell vaccines delivered in combination to safely induce anti-HCV and anti-HIV T cell immunity simultaneously in a single host. 
Type Therapeutic Intervention - Vaccines
Current Stage Of Development Early clinical assessment
Year Development Stage Completed 2014
Development Status Under active development/distribution
Impact Clinical trial is recruiting. 
 
Title RIVER 
Description Assessment of decreasing latent HIV pool by reactivation and vaccination 
Type Therapeutic Intervention - Vaccines
Current Stage Of Development Early clinical assessment
Year Development Stage Completed 2014
Development Status Under active development/distribution
Impact Testing in process 
 
Description Adjacent Governmant article 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? Yes
Geographic Reach International
Primary Audience Policymakers/politicians
Results and Impact Articles describing the importance of our research

Invitations to do more
Year(s) Of Engagement Activity 2014
 
Description International Innovation Article 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? Yes
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Dissemination of science, research and technology

Many more requests from similar journals
Year(s) Of Engagement Activity 2014
 
Description NDM Podcast 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact The podcast is available on the Univesity wensite.

Public understading.
Year(s) Of Engagement Activity 2012
 
Description Race for Life 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? Yes
Type Of Presentation Workshop Facilitator
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Team building exercise
Websites:
http://www.ccmp.ox.ac.uk/public-engagement
http://www.raceforlifesponsorme.org/kessler-group/eurl.axd/289728e11b02e2478608452b80d5ec5e

Raising awareness for sport as a way to increase health
Year(s) Of Engagement Activity 2012