Report from working group C

Further Research and Development

Six Presentations

• Review of new vaccine platforms and vaccine pipelines - Rick Bright

• Correlates of protection in the evaluation of vaccine efficacy: current concepts and research – Arnold Monto

• Research on new vaccine delivery methods -Bruce Weniger

• Perspectives from industry – Giuseppe del Giudice

• Overview of financial activities on influenza vaccine research – Robin Robinson

• WHO activities on influenza vaccine research –John Tam

Egg-basedinactivated

Cell-cultureinactivated

LAIV

Recombinant (VLPs)

Universal

Vectors

SERUM INSTITUTE OF

INDIA LTD

WIVWIVEgg inactivated H5N1 WIV +Alum SplitH5N1 Surface

antigen w/ AlPO4 Split Split

H5N1 AS03WIV Split WIV H9N2 virosomal & whole

H5N1 Surface Antigen +Alum H5N1 WIV w/ Adjuvant Proteosome intranasalProprietary Adjuvant SplitSplitWhole Virion Adimmune- TaiwanH5N1 Split w/ AF03 H1N1 Split w/ AF03

H5N1, WIV WIV

InstitutulCantacuzino

Split

MDCK H5N1H5N1 EB 66 CellsMDCK Influvac TC

subunit (Netherlands) Monkey Kidney Cell H1N1 Cell; HN-VAC (India)

MDCK subunit (EU) US 2009/2010

Vero, Influject/ Cevapan(EU)

Vero, Influject/ Cevapan(US)

MDCK subunit US (S)

SIIL

Egg

MDCK H5N1 dNS1 - Vero Egg H5N1/H9N2 Cell Egg, H5N2 Egg, Thailand

Serum Institute of India Ltd

EggEgg Egg (Russia)

dNS1- Vero

VLP / HA VLP, Insect cells VLP, 293 cells rHA, Plants rHA Insect cells VLP, Plants rHA, Insect cellsVLP, Insect Cells

Salmonella, Oral VLP, Fungus Yeast, IN - Oral

Salmonella, OralChimeric VLP + microneedles VLP, insect cells

Molecular HAs

NYU / MSSMHA Fusion Peptide M2 Protein Peptides from HA & NP M2e Novel peptides

M2e M2e flagellin

NP & ISS Tech Peptide based

HA, Flagellin, e coli

MVA Based Adenovirus M & NP Adenovirus Adenovirus, Oral Split

Alphavirus

MVA

MVA Based Adenovirus, OralAdenovirus

DNADNA / Vaxfectin

DNA / Vaxfectin DNA

DNA / SnyCon w/ Electroporation H5

Seasonal

Pandemic

Seasonal & Pandemic

US License

Influenza Vaccine Landscape

Updated: 07/07/2011

M2e Liposome

rHA, Plants rHA, Plants

DNA / SnyCon w/ Electroporation

rHA Insect Cells

Mass Gen HospitalListeria

Correlates of protectionCorrelates of protection

�� Revisit the precise role of HAI antibody in Revisit the precise role of HAI antibody in

protection using contemporary endpointsprotection using contemporary endpoints

�� Understand better the role of antigenic drift, Understand better the role of antigenic drift,

concentrating initially on concentrating initially on hemagglutininhemagglutinin

�� Further develop of standards Further develop of standards --HAI and MN first, HAI and MN first,

then moving to those elements of CMI responsethen moving to those elements of CMI response

�� Identify whether correlates are different with Identify whether correlates are different with

different vaccine formulations and vaccine match; different vaccine formulations and vaccine match;

different age groups; further work necessary for different age groups; further work necessary for

LAIVLAIV

�� Use efficacy trials results to provide updated data Use efficacy trials results to provide updated data

on correlates of protection; data sharing?on correlates of protection; data sharing?

New Delivery Methods Influenza – potential dose sparing and needle free

• Cutaneous, including Classic Intradermal (ID)

� Improving on Dr. Mantoux’s ID Method

� Mechanical Disruption of Stratum Corneum

� Coated Microtines

� Hollow Microneedles

� Dissolving Microneedles

� Other (Kinetic, Electromagnetic, Chemical, Sonic)

• Jet Injection

• Intranasal Spray

• Pulmonary Inhalation of Wet/Dry Aerosols

• Oral Ingestion

Perspectives from Industry

• Industry is playing a key and active role

• Demand drives supply

• New vaccines have been successfully introduced (adjuvanted, cell-derived, intradermal, high-dose)

• Need for constant, open dialogue with broad range of stakeholders (e.g. regulatory, public sector)

77

BARDA ARD

NIH

Vaccine Developmentis Risky, Lengthy, & Expensive

3-7 yr 0.5-2 yr 1-2 yr 2-3.5 yr 2.5 -4 yr 1-2 yrs TIMETIME

$100M -130M $60-70M $70M-100M $130M-160M $190M-220M $18M-20MPIPELINEPIPELINEPHASE COSTPHASE COST

“Valley of Death”

Discovery Phase I Phase II LicensurePhase IIIPreclinical

DevelopmentProduction & Delivery

PROBABILITY OF SUCCESS TO LICENSURE

PR

OD

UC

T P

IPE

LIN

EP

RO

DU

CT

PIP

ELIN

E

LicensedProduct

1-3% 5-17% 10-25% 18-35% 45-70% 90%

IND BLA

PHASESPHASES

NIH ($11.8B)

BARDA ($540M)

Project BioShield ($5.6B)

Discovery Phase I Phase II LicensurePhase IIIPreclinical

DevelopmentProduction & Delivery

PROBABILITY OF SUCCESS TO LICENSURE

PR

OD

UC

T P

IPE

LIN

EP

RO

DU

CT

PIP

ELIN

E

LicensedProduct

1-3% 5-17% 10-25% 18-35% 45-70% 90%

IND

PHASESPHASES

NIH

BARDA

BARDA

88

Changing Tides for Influenza Vaccine R&D Funding Sources

$100’s M

$10’s B $1’s B

Robin Robinson, BARDA

DiscussionVaccine development - general

• Goal with vaccine development – more, better, sooner, and lower cost

• R&D landscape: active, evolving rapidly but significant challenges ahead and need for continued stakeholder support

• As funding decreases, strategic prioritizing becomes more important

• Regulatory challenges for novel vaccines and new technology– Correlates of protection

• While a long-term goal, R&D into “universal”vaccines should remain a priority

Discussion- Sustainability“What will keep factories going?”

• “Risk-benefit ratio” - Understanding safety and impact of vaccines, both current and new vaccines, is critical– Vaccine probe studies (BOD)

– Innovative, cost-efficient trial designs

• Outcomes that will resonate with decision makers and public– Impact on maternal and child health

– Impact on pneumonia/death reduction in all ages

– Impact on health care infrastructure and quality

• Multi-purpose facilities

DiscussionOther priority research topics

• Improving vaccine performance• Immunogenicity, duration of protection, cross-protection,

additional strains• Development of criteria for progressing candidates

• Better, faster, lower cost• Regulatory

– Catalytic and coordinating role of WHO for technical assays (immune, release), pharmacovigilance, vaccine quality

• Delivery of vaccine– Technology– Stability– Operational: e.g. time-in-motion studies

Discussion

• Identify clear short, medium and long-term goals

• Assumptions should be explicit and periodically revisited

• Define clear roles and responsibilities of WHO and other stakeholders