the vaccine formulation laboratory - whothe vaccine formulation laboratory university of lausanne,...
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The Vaccine Formulation Laboratory
FIFTH MEETING WITH INTERNATIONAL PARTNERS ON
PROSPECTS FOR INFLUENZA VACCINE TECHNOLOGY TRANSFER
TO DEVELOPING COUNTRY VACCINE MANUFACTURERS
Nicolas Collin, Beograd, 28 March
2012
Adjuvant Hub &
Training Center on Vaccine
Formulation
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The Challenge of Access to Adjuvants
Adjuvants: substances added to vaccines to improve specific immune response
• Increase antibody titers, induce long-lasting immunity
• Trigger cell-mediated immunity
• Enable immunization in weakened immune system
• Reduce antigen dose and number of doses: antigen-sparing
Essential components of modern vaccines
Access to adjuvants and to vaccine formulation know-how is difficult for:
• Developing Countries Vaccine Manufacturers
• Public Sector
• Biotech Companies
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January 2010: creation of the Adjuvant Hub
The Vaccine Formulation Laboratory
University of Lausanne, Switzerland
WHO Collaborating Centre in Immunology
March 2012: VFL at a glance
6 grants and respective programmes currently on going
Over 20 collaborations with academics, industries, DCVM
Expansion of adjuvant portfolio, laboratory space & staff
October 2010: 1st grant from HHS / BARDA
Technology transfer of oil-in-water adjuvants
to DCVMs for pandemic influenza vaccines
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SOPsSOPs SOPs
GMPVaccine developer - DCVM
Lausanne Training platform Preclinical / GMP-compatible
Advice
ManufactureFormulation
with antigenQC Preclinical Clinical trials
Choice of
adjuvant
SOPs
How do we work?
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Trainings at the VFL – a la carte
• 1. Vaccine formulation: optimized combination of antigens and
adjuvants, stability of formulations, etc.
• 2. Quality Control assays of adjuvanted vaccines
• 3. Preclinical evaluation of adjuvanted vaccines
• Stability studies
• Head-to-head studies in animal models
• Immunological read-outs (Humoral, T-cell responses)
• 4. Technology transfer of adjuvant technology
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The BARDA project
Example: Pandemic influenza vaccine
Development and Sustainable Manufacturing of Adjuvanted Pandemic Influenza
Vaccines in Developing Countries
OCT 2010 - OCT 2011
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Bio Farma - adjuvanted H5N1 vaccine development
SOPsSOPs SOPs
Lausanne
Advice
ManufactureFormulation
with antigenQC Preclinical Clinical trials
Choice of
adjuvant
SOPs
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Adjuvant for pandemic influenza vaccines
H2O
H2O
OIL
H2OH2OH2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
Technology selected: squalene-in-water emulsion
• Emulsions vary in their composition and biology
• Technology used is licensed since 1997:
most mature adjuvant technology after aluminium salts
• Tens of millions of doses distributed (seasonal and pandemic influenza
vaccines), no severe adverse events
Remarkable dose-sparing effect with H5N1 influenza split / subunit vaccines
2 doses of 90µg (HA) without adjuvant > 2 doses of 7.5µg (HA) with adjuvant
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Transfer of adjuvant technology to Bio Farma
• December 2010: Kick-off meeting in Bandung, project team
• March 2011: First training at the VFL
• May 2011: On-site visit in Bandung
• June 2011:
• Pilot-scale and QC facilities installed - SOP transferred and translated
• 3 consistency lots manufactured
• QC performed at both sites
• GMP documentation list drafted
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Oil-in-water emulsion characteristics
RP-HPLC squalene content in BF emulsion Particle size of BF emulsion
0
20
40
60
80
100
120
140
160
180
0 100 200 300 400
Par
ticl
e d
iam
eter
, nm
Days
Stability of BF emulsion over time (2-8 °C) Adjuvant activity of emulsion in mice (HI)
- formulated with H5N1 turkey/Turkey (2 ug)
ADJ - + - + - +
DAY 0 21 35
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Much more than 3 lots
• Technology transfer completed in 9 months
• Project is continuing:
- optimization of process development
- new adjuvant lots produced on regular basis at Bio Farma
- preclinical evaluation of adjuvanted Bio Farma H5N1 vaccines
• One more step for Indonesia towards Pandemic Preparedness
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1) choose antigen of interest
Example of vaccines that we currently work with: Pandemic influenza, Shigella, E. Coli,
MenB, HepB, Inactivated Polio, Malaria, Lupus, HIV, Cancer, etc.
2) choose adjuvants: commercial, manufactured at VFL, MTA
Ex: aluminium salts (hydroxide, phosphate), water-in-oil emulsions, oil-in-water
emulsions, saponins, TLR4 agonists, liposomes, etc.
3) customized trainings in Lausanne or at your place of choosing
Current collaborators are from: Vietnam, Germany, Indonesia, The Netherlands, Ireland,
France, USA, South Korea, Italy, UK, India, etc.
VFL adjuvant services: to sum-up
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Hvala – thank you
• Roland Ventura
• Livia Brunner
• Patrice Dubois
• Simon Heuking
• Maude Marti
• Thérèse Sidibé
• Maria Lawrenz
• Aurélie Demierre
• Virginie Jakob
• Christophe Barnier
• Lana Cridland
• Chuong Huynh
• Michael O’Hara
• David Behnam
• Martin Friede
• Marie-Paule Kieny
• Mahendra Suhardono & colleagues
• Le Kim Hoa & colleagues
• All our collaborators and trainees over
the world!
• Otto de Boer & colleagues