WHO Cnsideratins fr Shigella vaccine develpment WHO s 2018 Prduct Develpment fr Vaccines Advisry Cmmittee meeting: A year in review BMGF Shigella Internatinal ELISA and Standards Wrkshp Birgitte Giersing, PhD Initiative Birgitte K. Giersing fr Vaccine Lndn 5 Research, December 2017 WHO 26 th June 2018
What des PDVAC d? PDVAC s missin is t accelerate prduct develpment f vaccines and technlgies that are urgently needed and ensure they are apprpriately targeted fr use in lw and middle incme cntexts. Vaccine candidates Mnclnal antibdies Delivery technlgies
What des PDVAC d? Hrizn scanning f vaccine in early clinical develpment Evaluates prbability f technical and regulatry success and a rle fr WHO Unmet public health need fr a vaccine frm an LMIC perspective and cmmunicate pririties
What is the prblem we are trying t slve? Prduct Prduct Translatin gap Launch Implementatin gap Intrductin Discvery Preclinical Phase I-III Registratin WHO plicy & PQ Implementatin studies Financing & Prcurement Uptake
Hw des PDVAC wrk? Preferred prduct characteristics and the glbal preferred prduct prfile describe vaccine preferences Pathgen-specific guidance fr LMIC use PPC: Indicatin, target ppulatin, schedule, efficacy target, rute f admin. gppp: Frmulatin, primary cntainer, packaging Radmaps and pathway cnsultatins facilitate hw t achieve PPCs Cnsideratins fr prduct develpment pathways Vaccine radmap Develped by PDVAC Develped by Vaccine Presentatin and Packaging Advisry Grup (VPPAG)
WHO PPCs seek t braden the scpe f Target prduct prfiles (TPPs)* t incrprate LMIC market Parameter WHO PPC TPP Fcus Pathgen-specific Candidate (prduct) specific Cntent Audience Describes preferences fr LMICs Any entity seeking eventual PQ/LMIC market Sets minimal criteria fr develpment Stakehlders interested in return n investment Pathgen-specific guidance fr LMIC use PPC gppp PPCs infrm Candidate Specific target prduct prfiles (TPPs) TPP Purpse Encurage innvatin, braden vaccine target ppulatins Guide investment decisin making Prcess f develpment Public health stakehlder cnsultatin Within institutins * TPPs are develped by ther stakehlders and entities, typically private industry
Full Public Health Value Prpsitins (FPHVP)* fr Vaccines Meeting f the Strategic Advisry Grup f Experts (SAGE) n Immunizatin, Geneva, 17-18 April 2018 7 TITLE frm VIEW and SLIDE MASTER July 19, 2018
Full Public Health Value Prpsitins (FPHVP)* fr Vaccines Meeting f the Strategic Advisry Grup f Experts (SAGE) n Immunizatin, Geneva, 17-18 April 2018 *Full public health value f vaccines (FPHVV) 8 TITLE frm VIEW and SLIDE MASTER July 19, 2018
What is the prblem we are trying t slve? Prduct Prduct Translatin gap Launch Implementatin gap Intrductin Discvery Preclinical Phase I-III Registratin WHO plicy & PQ Implementatin studies Financing & Prcurement Uptake Articulating the public health value, PPCs, radmaps early in prduct develpment help t define the value prpsitin, encurage investment and mitigate against the implementatin gap
Human Immundeficiency virus (HIV) Tw HIV vaccine candidates are currently in late stage clinical trials in HIV-uninfected ppulatins, as heterlgus prime-bst appraches. mab als in late stage. Data anticipated in 2020-21 2017 PDVAC recmmendatin: Facilitate scenari planning and develpment f cmmunicatin strategies in preparatin fr HIV vaccine and mnclnal antibdy study utcmes. Evaluate the develpment pathway beynd nging prf-f-cncept studies. Identify gaps in guidelines t supprt licensure, availability and use in LMICs February 2018: Frm prf f efficacy t plicy decisin, access and use f prduct fr passive and active immunizatin t prevent HIV infectin: Prepare fr Success
Tuberculsis (TB) Primary strategic public health gal: reductin f disease in adlescents and adults Seven tuberculsis vaccine candidates in phase II clinical studies, and ne in phase III. 2017 PDVAC recmmendatin: Cntinue t facilitate and seek t accelerate develpment f vaccines fr preventin f tuberculsis in adults and adlescents Develpment f a PPC fr this indicatin. Octber 2017: WHO Initiative fr Vaccine Research & Glbal Tuberculsis Prgram Cnsultatin n Tuberculsis Vaccine Research and Develpment PPC published
Malaria Prgress twards start f RTS,S/AS01 pilt implementatin studies Fractinal RTS,S/AS01 dse regimen with ptential fr increased prtectin : nging evaluatin Prgress in several areas f translatinal clinical develpment, including investigating IV administratin f attenuated sprzites Past WHO PPC and radmap date back > 5 years. Warrants recnsideratin fr secnd generatin malaria vaccines.
Influenza WHO Preferred Prduct Characteristics fr Next-Generatin Influenza Vaccines have been published. Several candidate vaccines designed t elicit antibdies t cnserved epitpes n the hemagglutinin head r stem are advancing t early stage clinical develpment with the gal f achieving brad and durable immunity. BMGF meeting n Influenza Human Challenge Mdel fr universal flu vaccine develpment
Entertxigenic E.cli (ETEC) Accrding t the mst recent IHME estimates, ETEC mrtality has declined BUT causes 75 millin episdes f diarrhea each year During VASE 2018, BMGF annunced t phase ut investment in ETEC vaccine develpment due t lwer perceived burden and technical feasibility The leading ETEC vaccine candidate has advanced t a Phase IIb prf-f cncept field study in adult travelers; data expected 2019 Same candidate has cmpleted a phase II study in infants and children in Bangladesh 2017 PDVAC recmmendatin: Develp PPCs and clarity n develpment pathways fr use in LMICs Octber 2017: ETEC Vaccine Preferred Prduct Characteristics (PPCs) February 2018: Jint WHO-NIAID-PATH Wrkshp n develpment and standardizatin f ETEC assays and antigens
Shigella Accrding t IHME, Shigella is the secnd mst deadly diarrheal disease. WHO AMR pririty list Clinical pipeline f subunit, live and killed appraches Three next generatin O-Ag based vaccines priritized by BMGF, with a view t understanding hw CHIM can accelerate licensure 2017 PDVAC recmmendatin: Develp PPCs and clarity n develpment pathways fr use in LMICs Octber 2017: Shigella Vaccine Preferred Prduct Characteristics (PPCs) May 2018: WHO Cnsultatin n Prduct develpment and Plicy pathways fr O- antigen based cnjugate Shigella vaccines
Respiratry Syncytial Virus (RSV) Prgress in vaccine indicatins fr maternal immunizatin and mnclnal antibdies Lead candidate Ph3 evaluatin prgressing, having successfully passed a futility analysis Multiple gaps identified n the pathway t future implementatin in LMICs Cllabrative platfrm n maternal immunizatin, driven by RSV WHO R&D and technical radmap and PPC available WHO AC set up, wrk expanding fr preparing cnsideratin fr plicy decisin
Grup B streptcccus (GBS) Currently tw GBS vaccine candidates underging clinical evaluatin, with several in preclinical develpment. Effrts t characterize f the relatinship between levels f antibdies and prtectin are cntinuing in parallel with cnsultatins regarding an acceptable regulatry rute t licensure and plicy decisin. 2017 recmmendatins: Pursue effrts t identify a crrelate f prtectin. Evaluate the vaccine value prpsitin cnsidering health, ecnmic and scietal dimensins. WHO PPC and Radmap publically available December 2017: GBS vaccines: the rle f crrelates f prtectin in the pathway t licensure and plicy February 2018: WHO Scientific Advisry Grup t prvide inputs t the develpment f a value prpsitin fr Grup B Streptcccus (GBS) Vaccine
Grup A streptcccus (GAS) New burden estimates: An estimated 18 millin peple suffer frm a serius GAS disease, and 1.8 millin new cases and 517,000 deaths ccur annually. The greatest burden is due t rheumatic heart disease, but invasive GAS diseases (including maternal and nenatal sepsis) als cntribute significantly 2018 WHA reslutin n Rheumatic Fever and Rheumatic Heart Disease 2017 recmmendatins: Evaluate the vaccine value prpsitin cnsidering health, ecnmic and scietal dimensins. WHO PPC and Radmap publically available May 2018: WHO Cnsultatin n GAS vaccine research and develpment Renewed cnsensus develpment pathway, active cllabratins n the value prpsitin
Herpes Simplex Virus (HSV) Prphylactic HSV2 vaccines are preferred fr LMICs, but current clinical candidates being tested as therapeutic vaccines Therapeutic vaccines have demnstrated clinical POC, but have nt prgressed Therapeutic HSV2 candidates culd have ppulatin impact in LMICS if able t reduce HSV2 transmissin and/r HIV acquisitin, as well as GUD Need t articulate strng value prpsitins fr prphylactic and therapeutic HSV vaccines in LMICs HSV PPC drafted Several activities underway t strengthen the full public health value f HSV vaccines Estimates f HSV GUD, HSV-2-assciated HIV, HSV-1 utcmes HSV ecnmic burden HSV vaccine impact mdeling
Nucleic acid vaccine (NAVs) platfrms Advances in the in viv expressin, stabilizatin and delivery f bth RNA and DNA have imprved the prspects fr immunizatin by NAVs. Increasingly, NAV vaccines are cnsidered t be a ptential game changer fr epidemic and pandemic respnse due t the expectatin that they may be significantly faster and cheaper t manufacture, simpler t administer, and ptentially mre effective than cnventinal vaccines. WHO Cnsultatin held t determine whether the existing DNA guidelines were due fr revisin r if they remained relevant with tday s status f nucleic acid vaccine develpment and maturity twards licensure February 2018: Prduct develpment and prgrammatic cnsideratins fr nucleic acid based vaccines & WHO Cnsultatin n Nucleic acid vaccine guidelines
Micrarray patch prduct develpment fr MR vaccines Recmmendatin by SAGE, Octber 2016: SAGE acknwledged the imprtance f peratinal and technlgical research t address the barriers t achieving GVAP [Glbal Vaccine Actin Plan] measles and rubella gals. In particular, SAGE recmmended that the mst expeditius clinical develpment and regulatry pathway t licensure f measles cntaining vaccines (MCV) micr-array patch (MAP) be determined, and that barriers t the develpment, licensure, and use f MAPs fr measles and rubella vaccine delivery be identified and addressed urgently. March 2018: Measles cntaining vaccines (MCV) Micrarray Patch (MAP) prduct develpment
Nvel appraches t priritize vaccine innvatins t imprve cverage and equity Vaccine cverage fr rutine vaccines has failed t reach the glbal targets f 90% using current delivery strategies. Develpment and uptake f nvel vaccines, delivery appraches and delivery technlgies are needed t reach the immunizatin targets
Nvel appraches t priritize vaccine innvatins t imprve cverage and equity Gavi, WHO, Unicef, PATH and BMGF are wrking tgether t develp tw new tls t identify and priritise high impact innvatins that meet the preferences and pririties f lw and middle incme cuntries Ttal Systems Effectiveness (TSE) is a hlistic apprach t evaluate and priritize vaccine innvatins, by cnsidering their ptential t increase the cverage and t infrm nvel vaccine innvatins thrugh Vaccine Innvatin Priritizatin Strategy (VIPS).
WHO versight and guidance f vaccine prduct develpment and intrductin Early-stage value prpsitin Late-stage value prpsitin Discvery WHO Regist Implement Preclinical Phase I Phase II Phase III plicy F&P Uptake ratin n studies & PQ PDVAC: Early stage (pre-phase II POC) IVIR-AC: Plicy preparatin & decisin-making IPAC PQ SAGE PDVAC: Prduct Develpment fr Vaccines Advisry Cmmittee IVIR-AC: Immunizatin and Vaccines-related Implementatin Research Advisry Cmmittee IPAC: Immunizatin Practices Advisry Cmmittee SAGE: Strategic Advisry Grup f Experts n Immunizatin PSPQ: Prequalificatin
Glbal Vaccine and Immunizatin Research Frum (GVIRF) Bangkk, March 2018 C-hsted by WHO, the Natinal Institute f Allergy and Infectius Diseases, and the Bill & Melinda Gates Fundatin. All research aspects related t the Glbal Vaccine Actin Plan (GVAP) Pathgen and crss-cutting tpics such as expanding and leveraging DCVMs, maternal and adlescent immunizatin platfrms, innvating fr equity Tracks prgress, identifies gaps, creates alignment and crdinates activities t increase the efficiency and impact f activities and resurces. http://www.wh.int/immunizatin/research/frums_and_initiatives/gvirf/frum_2018/en/
References Generic Preferred Prduct Prfile fr Vaccines (gppp) http://www.wh.int/immunizatin/plicy/cmmittees/vppag_generic_ppp_and_wrkplan.pdf?ua=1 Assessing the prgrammatic suitability f vaccine candidates fr WHO prequalificatin (Revisin 2014) http://apps.wh.int/iris/bitstream/10665/148168/1/who_ivb_14.10_eng.pdf?ua=1 IVR vaccine PPCs and Radmaps: http://www.wh.int/immunizatin/research/ppc-tpp/preferred_prduct_characteristics/en/