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Jenner Institute Complementary Vaccines Platform Technologies

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Jenner Institute Complementary Vaccines Platform Technologies WHO R&D Blueprint: Janssen Vaccines – Jenner Institute complementary Vaccines Platform Technologies Janssen Vaccines: Jenner Institute: Olga Popova Prof. Sarah Gilbert Jerome Custers WHO Geneva, 21 July 2016 Background • Jenner Institute & Janssen Vaccines presented respective proposals to WHO R&D Blueprint Workshop in April 2016, and were invited to join forces for Round 2 submission • Example of alignment, coordination and partnership between public and private sector stakeholders • Understanding nature of vaccine development, established complementary end‐to‐end skills and capabilities • Long‐term, sustainable & consistent approach and funding • High‐level flexible proposal with illustrative examples • «Bona fide»: collaborative framework to be developed JOINTLY TOWARDS TANGIBLE OUTCOMES x GLOBAL PUBLIC HEALTH 2 Success factors • Available platforms and previous experience with pathogens • Ability to invest time and resources, leverage expertise, minimise opportunity costs and ensure business continuity • Appropriate and functionable operational model, speed • Lean governance, partner alignment and milestone orientation INTERNAL • Reliable & qualified partners, durable commitments • Long‐term reliable funding (min 5‐year horizon) • Resolving vaccination indemnification / liability issue • Consistency in pathogen prioritisation and defined, consistent pre‐ established endpoint commitment • Clear and accelerated / streamlined regulatory pathways, conditions & predictability of licensure EXTERNAL • Anticipated deployment plans and community engagement 3 Jenner ‐ Janssen Partnership: Vaccine Technology Platforms Janssen Vaccines Jenner Institute PER.C6® cell line technology for manufacturing Adenoviral vector technology Whole inactivated vaccines Chimpanzee‐derived adenovirus‐based Attenuated vaccines Extensively clinically tested Recombinant protein or subunit vaccines Thermostabilisation technology for storage at Adenoviral vectors temperatures up to 45C for six months, or ambient temperatures for much longer Modified Vaccinia viral vector technology Adenoviral vector technology Capacity to express multiple antigens Low‐seroprevalent adenovirus‐based Proprietary strong promoters and insertion Extensively clinically tested sites High capacity/low cost manufacturing using PER.C6® cell Access to manufacturing in immortal avian cell line technology lines Liquid formulation compatible with current vaccine Virus Like Particle Technology supply chains: HBsAg fusion VLPs produced in yeast o Current liquid formulation; 1 year stability at 2‐8C AP205 VLPs produced in E. coli o New formulation with at least 2 year real time in vitro stability at 2‐8C 4 The Jenner Institute founded 2005 • Global Health – vaccines that make a difference • HIV, TB, malaria, dengue, pandemic influenza • Emerging pathogens • Translational Research – rapid early clinical testing • 42 vaccines made for clinical trials • One Health – vaccines for humans and other animals 5 Human Vaccines Pipeline a portfolio approach Number Disease Area of GMP Preclinical Phase I Phase IIa Phase Ib Phase IIb Phase III Licensure Vaccines Oxford Patient Group /Endemic Area Malaria 19 TB 4 HCV 3 HIV 5 Pandemic Flu 2 Meningitis 1 RSV 3 Ebola 4 Prostate cancer 2 Staph aureus The busiest pipeline of any non-profit vaccine institute 6 Clinical BioManufacturing Facility University of Oxford This image cannot currently be displayed. This image cannot currently be displayed. 7 Rapid Clinical Trial Capacity • Over 150 clinical trials undertaken in the last decade – over 100 of these with vaccines designed / manufactured in Oxford – over 2000 volunteers enrolled in UK trials per annum – Allows rapid down‐selection of the most promising candidates 8 Challenge Trials or controlled human microbial infections (CHMI) • Malaria – Sporozoite – Blood-stage • Influenza • BCG for TB • Typhoid • Paratyphoid • (RSV) 9 Overseas Trials • KEMRI‐Wellcome Programme, Kilifi, Kenya • Kenyan AIDS Vaccine Initiative Nairobi, Kenya • South African TB Vaccine Initiative, Western Cape • MRC Laboratories, The Gambia • Cheikh Anta Diop University, Dakar, Senegal • CNRFP, Ouagadougou, Burkina Faso • Uganda Virus Research Institute, Entebbe, Uganda • Patan Hospital, Kathmandu, Nepal 10 Replication‐Deficient Viral Vector Vaccines to Maximise both Humoral and Cellular Immunogenicity Rapid initial response plus extended duration of immunity 1 - 8 weeks Adenovirus Prime MVOxford Boost Malaria x 6, HCV, HIV, influenza, TB, RSV, Ebola, prostate cancer 11 Outbreak Pathogen Vaccine Progress Current status Pathogen Construct Immuno‐ Neutralisation Animal GMP Phase Made genicity Efficacy funded I/II Pandemic Flu Rift Valley Fever MERS Zika Chikungunya CCHF Lassa Ebola Zaire Ebola Sudan Ebola x2 + Marburg Marburg Nipah SARS 12 Strong T Cell Responses with a One Week Prime‐Boost Interval in Ebola ‐BN A Monovalent Chimpanzee Adenovirus Ebola Vaccine Boosted with MVA Ewer et al., NEJM 2016. 13 Antibody responses after prime and boost ‐BN A Monovalent Chimpanzee Adenovirus Ebola Vaccine Boosted with MVA Ewer et al., NEJM 2016. 14 ChAdOx1 RVF can be thermostabilised 512 Vaccine thermostabilised p=0.2 256 Stored at various ºC for 6 months 128 Vaccine reconstituted to same dose 64 Cattle immunised, single dose 32 Anti-RVFV antibodies measured Neutralising antibody titre 16 d ºC e 5ºC 80 25ºC 37ºC 45ºC 5 at - in cc va Un For thermostabilisation method see: Alcock R, et al Sci Transl Med 2010 Feb 17;2(19) 15 Jenner ‐ Janssen Partnership: Vaccine Technology Platforms Janssen Vaccines Jenner Institute PER.C6® cell line technology for manufacturing Adenoviral vector technology Whole inactivated vaccines Chimpanzee‐derived adenovirus‐based Attenuated vaccines Extensively clinically tested Recombinant protein or subunit vaccines Thermostabilisation technology for storage at Adenoviral vectors temperatures up to 45C for six months, or ambient temperatures for much longer Modified Vaccinia viral vector technology Adenoviral vector technology Capacity to express multiple antigens Low‐seroprevalent adenovirus‐based Proprietary strong promoters and insertion Extensively clinically tested sites High capacity/low cost manufacturing using PER.C6® cell Access to manufacturing in immortal avian cell line technology lines Liquid formulation compatible with current vaccine Virus Like Particle Technology supply chains: HBsAg fusion VLPs produced in yeast o Current liquid formulation; 1 year stability at 2‐8C AP205 VLPs produced in E. coli o New formulation with at least 2 year real time in vitro stability at 2‐8C 16 Janssen Vaccines expertise • Proven technology platforms, expert teams • PER.C6® cell line unique characteristics and ability to apply for multiple pathogens • Process development, manufacturing capabilities and scale up (>1 mio Ebola vaccine regimens in 1 year, potential for >300.000 doses / week). Optimised temperature stability for field use • Clinical development capabilities and know‐how in potentially affected areas and resource‐limited settings • Managing multilateral partnerships (eg. Ebola IMI) 17 Core Technology Platforms Supporting Janssen Vaccine Development PER.C6® cell line technology . For the manufacturing of: – Whole inactivated virus vaccines – Attenuated virus vaccines – Viral vectors – Protein vaccines and monoclonal antibodies . Highly permissive to human and animal viruses . Culturing at high cell density results in increased volumetric productivities lowering demand of scale and COGs 18 Development of the PER.C6® cell line History of the PER.C6® cell line . Primary human retinoblasts were obtained in 1985 from a healthy donor . Immortalized using adenovirus E1A/E1B in 1995 . Human cell substrates have been used for the manufacture of numerous live attenuated vaccines in the past 40 years . To date >60 material and IP licenses granted for applications with gene therapy vectors, vaccines and recombinant proteins . Tested in compliance with applicable regulations and guidances from US FDA, EU, ICH and WHO . Biologics Master File available at FDA 19 PER.C6® cells: for the replication of human viruses for vaccine manufacturing Picornaviridae Flaviviridae Paramyxoviridae PV1, 2, 3 ZIKV PI 1,2,3 Coxs A9, B2, B4 WNV NDV Echovirus, 7, 11 JEV Measles EV71 YF RSV Togaviridae Herpesviridae Adenoviridae SF HSV‐1 Human AdV Sindbis HSV‐2 Ape AdV Rhabdoviridae Reoviridae Poxviridae VSV Rhesus RV Vaccinia Rabies Human RV Orthomyxoviridae Bunyaviridae Influenza Hantaan 20 PER.C6® cells support substantially higher production of poliovirus than VERO cells Sabin strain yields are greatly enhanced on the PER.C6® cell platform Sanders et al., 2015. Vaccine 33 (48): 6611–6616 Sabin strain yields on the PER.C6® cell platform are maintained at larger scale and provides a high capacity, low cost option for Sabin‐IPV manufacturing Strain Scale # of runs Average Productivity at harvest (D antigen/ml) # doses / ml* Sabin 1 10L 7 2285 > 200 Sabin 2 10L 5 379 > 25 Sabin 3 10L 3 3098 > 40 *Dose assumption: Type 1:2:3 = 10:15:70 D antigen units/dose 21 HIV vaccine development: PER.C6®-derived vaccines provide protection against SHIV challenge Ad26 prime – Env GP140 boost vaccinations in NHP provide increased protection in stringent SHIV-SF162P3 and SIVmac251 challenge models (Science. July 2015 and unpublished data) • NHP study #13-19: BIDMC/MHRP/Janssen collaboration • The Ad26/Ad26+gp140 HIV vaccine regimen provides substantial protection against repetitive (6) rectal SHIV challenges
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