Development of a universal HIV-1 vaccine

Lead Research Organisation: University of Oxford
Department Name: Experimental Medicine

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 the enormous HIV variability, which dwarfs 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 simple candidate vaccine designed specifically to overcome the HIV variability by focusing the body defences on the conserved viral parts. Here, we are proposing to test this approach for the first time in a small pilot study in healthy individuals in Oxford. Successful outcome of this study would strongly support further evaluation of this vaccination strategy in larger and more expensive clinical studies.

Technical Summary

This proposal will test for the first time in humans several novel, state-of-the-art technologies combined to provide maximum benefit to vaccinated individuals. First, one of the big roadblocks in development of HIV-1/AIDS vaccines is the enormous diversity of HIV-1, which could limit the value of any HIV-1 vaccine candidate currently under test. To address the HIV-1 variation, we designed a novel T cell immunogen, designated HIVconsv, by assembling the 14 most conserved regions of the HIV-1 proteome into one chimaeric protein. Each segment is a consensus sequence from one of the four major HIV-1 clades A, B, C and D, which alternate to ensure equal clade coverage. We demonstrated that these conserved regions prime CD8+ and CD4+ T cell to highly conserved epitopes in patients during natural HIV-1 infection and that these epitopes, although usually subdominant, generate memory T cells. Here, we propose to test the immunogenicity of the HIVconsv chimearic protein in a pilot small phase I trial in healthy HIV-1-uninfected individuals in Oxford to assess the breadth, specificity and cross-clade reactivity of the vaccine induced T cells. Second, we shall deliver the HIVconsv gene in a novel vaccine vector based on adenovirus of chimpanzee origin (AdC), which matches and possibly outperforms the currently perceived most immunogenic vaccine vector, human Adenovirus serotype 5 (AdHu5). Third, we shall use the AdC.HIVconsv vaccine in a heterologous prime-boost regimen of DNA/AdC/modified vaccinia virus Ankara (MVA) to further increase the vaccination potency. The HIVconsv-induced T cell responses will be assessed in a comprehensive analysis of frequency, phenotype and functionality, which will indicate according to pre-determined stringent criteria whether or not our vaccine strategy should advance to a larger proof-of-principle trial. In summary, our vaccination approach provides an attractive and testable alternative for overcoming the HIV-1 variability, while focusing T cell responses on regions of the virus that are less likely to mutate and escape. Furthermore, it has merit in the simplicity of design and delivery, requiring only a single immunogen to provide extensive coverage of global HIV-1 population diversity.

Publications

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publication icon
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 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 IAVI post-doctoral fellowship
Amount £50,000 (GBP)
Funding ID N/A 
Organisation International AIDS Vaccine Initiative (IAVI) 
Sector Charity/Non Profit
Country Global
Start 01/2014 
End 12/2014
 
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
 
Description Programme grant
Amount £1,322,832 (GBP)
Funding ID G1001757/1 
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 07/2011 
End 06/2016
 
Title 3 GMP candidate HIV-1 vaccines 
Description New candidate HIV vaccine 
Type Of Material Technology assay or reagent 
Year Produced 2009 
Provided To Others? Yes  
Impact Interest of peers, new collaborations, new grant submission 
 
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 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 CHERUB RIVER 
Organisation Imperial College London
Country United Kingdom 
Sector Academic/University 
PI Contribution Contributed to development of research proposal for submission to MRC DCS scheme. Contributed to development of clinical trial protocol. Contributed to immunological data analysis plan. Am contributing to project management and clinical trial steering.
Collaborator Contribution Led development of research proposal for submission to MRC DCS scheme Trial led by Imperial College.
Impact Application has now been funded by MRC. My group has undertaken the immunological assays for this trial. Data analysis will be completed in 2018.
Start Year 2012
 
Description CHERUB RIVER 
Organisation King's College London
Country United Kingdom 
Sector Academic/University 
PI Contribution Contributed to development of research proposal for submission to MRC DCS scheme. Contributed to development of clinical trial protocol. Contributed to immunological data analysis plan. Am contributing to project management and clinical trial steering.
Collaborator Contribution Led development of research proposal for submission to MRC DCS scheme Trial led by Imperial College.
Impact Application has now been funded by MRC. My group has undertaken the immunological assays for this trial. Data analysis will be completed in 2018.
Start Year 2012
 
Description CHERUB RIVER 
Organisation University of Cambridge
Country United Kingdom 
Sector Academic/University 
PI Contribution Contributed to development of research proposal for submission to MRC DCS scheme. Contributed to development of clinical trial protocol. Contributed to immunological data analysis plan. Am contributing to project management and clinical trial steering.
Collaborator Contribution Led development of research proposal for submission to MRC DCS scheme Trial led by Imperial College.
Impact Application has now been funded by MRC. My group has undertaken the immunological assays for this trial. Data analysis will be completed in 2018.
Start Year 2012
 
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 BCN01 in Barcelona 
Organisation HIVACAT Program IrsiCaixa Institute for AIDS Research
Country Spain 
Sector Multiple 
PI Contribution Providing knowhow, GMP vaccines and some reagents for a clinical trial BCN01 testing immunogenicity of HIVconsv vaccines in newly-infected patients treated with antiretrovirals within the first 6 months of infection.
Collaborator Contribution Cohort of patients identified during AHI, antiretrovirals drugs, running the trial and primary immunological assays.
Impact Trial approved, recruitment started.
Start Year 2012
 
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 Clinical trial HIV-CORE003 in London 
Organisation University College London
Department National Amyloidosis Centre
Country United Kingdom 
Sector Academic/University 
PI Contribution This an MRC DCS award to Prof Sir Mark Pepys, to which we are contributing know-how, GMP vaccines, immunological reagents and evaluation of immunogenicity output.
Collaborator Contribution Execution of clinical the trial HIV-CORE003, serum amyloid component P-depleting drug CHPHC.
Impact Multidisciplinary collaboration, the anticipated start of recruitment is March 2013.
Start Year 2012
 
Description Clinical trial HIV-CORE004 in Nairobi 
Organisation Kenya AIDS Vaccine Initiative (KAVI)
Country Kenya 
Sector Charity/Non Profit 
PI Contribution This is a EDCTP-funded clinical trial HIV-CORE004. We are providing know-how, GMP vaccines and immunological reagents and help with data analysis.
Collaborator Contribution Running of the clinical trial and primary safety and immunogenicity evaluations.
Impact Multidisciplinary, recruitment is planned to commence in March 2013.
Start Year 2012
 
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 testing of ChAdV63.HIVconsv 
Organisation Okairos
Country Italy 
Sector Private 
PI Contribution We provided to Okairos an HIV-1-derived immunogen gene, which was inserted in chimpanzee adenovirus 63 by company Okairos. We have tested the immunogen expression and induction of HIV-1-specific T cells in mice and rhesus macaques. Okairos owns the ChAdV-63 vector.
Collaborator Contribution Construction of ChAdV63.HIVconsv candidate vaccine against HIV-1 vectored by chimpanzee adenovirus 63.
Impact ChAdV63.HIVconsv has been highly immunogenic alone and in combination with other vaccine modalities. Construction has been completed, CHADV63.HIVconsv has been released to HIV-CORE002 trial, shelf-life stability tests and pre-clinical immunogenicity studies are on going
Start Year 2007
 
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 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 DNA electroporation 
Organisation Cellectis
Department Cyto Pulse
Country United States 
Sector Private 
PI Contribution Immunogenicity of electroporated DNA
Collaborator Contribution Expertise and instrument for DNA electroporation
Impact T cell immunogenicity of electroporated DNA alone and in combination with other vaccine modalities in mice and non-human primates are on-going
Start Year 2008
 
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 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 Development of a pan-filovirus vaccine 
Organisation Public Health Agency of Canada
Country Canada 
Sector Public 
PI Contribution Provision of research grade vaccines and design of a challenge experiments in mice and non-human primates
Collaborator Contribution Challenge and immunological and virological assays
Impact Protection of mice against lethal challenge with EBOV and MARV
Start Year 2017
 
Description GMP manufacture ChAdV63.HIVconsv/QP release 
Organisation University of Oxford
Department Nuffield Department of Clinical Medicine
Country United Kingdom 
Sector Academic/University 
PI Contribution Process Development for manufacture of ChAdV63.HIVconsv QP release of vaccines
Collaborator Contribution Process Development for and GMP manufacture of ChAdV63.HIVconsv QP release to GMP of ChAdV63.HIVconsv QP release to two trials of two MVA.HIVconsv and ChAdV63.HIVconsv vaccines
Impact Manufacture of a clinical batch of ChAdV63.HIVconsv has been completed at the university's Clinical BioManufacturing Facility and it was released to HIV-CORE002 trial
Start Year 2008
 
Description GMP manufacture of DNA vaccine pTH.HIVA 
Organisation Recipharm
Department Recipharm Cobra Biologics
Country Sweden 
Sector Private 
PI Contribution We designed and constructed an HIV-1-derived immunogene and the expression cassette, and used Cobra's Operator-Repressor Titration system for manufacture of plasmid with any antibiotic-resistance genes
Collaborator Contribution GMP products enable us to test novel vaccine concepts in humans
Impact GMP products enable us to test novel vaccine concepts in humans 19770697, 19266489, 18812202, 18440674, 17250931, 17170430, 17013989, 16641265, 16176847
 
Description GMP manufacture of MVA.HIVconsv/Qp release 
Organisation IDT Biologika GmbH
Country Germany 
Sector Private 
PI Contribution Manufacture of GMP MVA.HIVconsv
Collaborator Contribution GMP manufacture of MVA.HIVconsv vaccine and QP release to GMP
Impact Clinical batch of MVA.HIVconsv vaccine has been manufactured and released to two trials HIV-CORE001 and HIV-CORE002. Shelf-life stability tests are on going.
Start Year 2008
 
Description GMP manufacture of pSG2.HIVconsv DNA/QP release 
Organisation University of Bristol
Department School of Clinical Sciences
Country United Kingdom 
Sector Academic/University 
PI Contribution GMP manufacture and QP release of clinical batch of plasmid DNA
Collaborator Contribution Expertise in GMP manufacture of plasmid DNA vaccine pSG2.HIVconsv QP release to GMP and clinical trial
Impact GMP batch of plasmid DNA has been completed
Start Year 2008
 
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 HIV-CORE 003 
Organisation University College London
Department National Amyloidosis Centre
Country United Kingdom 
Sector Academic/University 
PI Contribution Design of clinical trial protocol
Collaborator Contribution Lead investigators of clinical trial combining our vaccines with an agent to improve responses to DNA vaccine through depletion of SAP
Impact Trial is completed.
Start Year 2012
 
Description IAVI-replication-competent virus vectors 
Organisation International AIDS Vaccine Initiative (IAVI)
Country Global 
Sector Charity/Non Profit 
PI Contribution MRC-owned insert HIVconsv is being inserted into IAVI-owned vectors by IAVI for joint preclinical and clinical collaborative studies
Collaborator Contribution Provision of highly-purified peptides for the immunologicla readout of HIVconsv-specific responses in animals and humans
Impact vector are being constructed
Start Year 2010
 
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 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 Pre-clinical toxicology 
Organisation Huntingdon Life Sciences
Country United Kingdom 
Sector Private 
PI Contribution Pre-clinical toxicology in mice
Collaborator Contribution Expertise in pre-clinical toxicology
Impact Two toxicology studies UNO0011 (MVA.HIVconsv) and UNO0012 (pSG2.HIVconsv and ChAdV63.HIVconsv), which support the MHRA applications to trials HIV-CORE001 and HIV-CORE002 have now been completed.
Start Year 2008
 
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 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 ChAV63.HIVconsv, MVA.HIVconsv, vorinostat 
Description Prime-boost HIV vaccine regimen given in combination with HDAC inhibitor vorinostat to HIV-positive patients who initiate antiretroviral therapy during primary HIV infection. 
Type Therapeutic Intervention - Vaccines
Current Stage Of Development Early clinical assessment
Year Development Stage Completed 2015
Development Status Under active development/distribution
Clinical Trial? Yes
Impact Recruitment and follow up completed. Data analysis on going. 
 
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 002 pTHr.HIVconsv, MVA.HIVconsv, ChAdV63.HIVconsv 
Description pTHr.HIVconsv, MVA.HIVconsv, ChAdV63.HIVconsv are HIV vaccine candidates that have been tested in 3 different prime-boost combinations in healthy HIV-negative volunteers. Safety evaluations have been completed. Immunogenicity analyses are ongoing. This work is funded by an MRC Experimental Medicine award for which I am a co-applicant. 
Type Therapeutic Intervention - Vaccines
Current Stage Of Development Early clinical assessment
Year Development Stage Completed 2012
Development Status Under active development/distribution
Clinical Trial? Yes
Impact Immunogenicity data have been published (PMID: 24166483). Other phase I studies are ongoing and funding has been obtained. 
URL http://clinicaltrials.gov/ct2/show/NCT01151319
 
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 Invited speaker 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Large audience

Publicity, awareness
Year(s) Of Engagement Activity 2012
 
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