INNOVATIVE VECTOR SYSTEMS, ADJUVANTS AND OTHER...
Transcript of INNOVATIVE VECTOR SYSTEMS, ADJUVANTS AND OTHER...
INNOVATIVE VECTOR SYSTEMS, ADJUVANTS AND
OTHER DELIVERY SYSTEMS
THE SCIENTIFIC CHALLENGES
Else Marie Agger
Infectious Disease Immunology
Statens Serum Institut
Denmark
New horizons for vaccine research and innovation, Bruxelles, 2014
ADJUVANTS OFFER A RANGE OF BENEFITS
Reed, Nature Medicine, 2013
MOVING FROM EMPIRICAL APPROACHES
1925: Ramon recognize that a variety of substances increase antigen
specific antibody production to diptheria and tetanus toxoids
1926: Glenny introduce aluminium salts as adjuvants
TIMELINE
1925 Adjuvant effect of: -Agar -Tapioca -Lecitin -Starch oil -Saponin -Bread crumps
1961 Thymus function
1968 T & B cells
1975 MHC
1986 TH1 & TH2
1996 Immuneact. by TLR
1973 DC’s
1994 TLR
1998 TLR-4 act. by LPS
ADJUVANTS IS A GROWING RESEARCH FIELD
PubMed search on vaccine adjuvants
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ADJUVANTS APPROVED FOR HUMAN USE
1920 1940 1930 1950 1960 1970 1980 1990 2000 2010
Aluminum-adjuvants
Virosomes
MF59
AS04
AS03
TIMELINE
EXAMPLES OF ADJUVANTS IN CLINICAL TESTING
Name Mechanism Profile
GLA-SE TLR4, emulsion Ab, Th1
AS01 TLR4, QS21 liposomes Ab, Th1
AS02 TLR4, QS21, emulsion Ab, Th1
AS15 TLR4 and 9, QS21, liposomes Ab, Th1, CD8
ISCOMS Unknown Ab, Th1/Th2, CD8
CD1d ligands CD1d Ab, Th1/Th2, CD8 NKT
CAF01 Mincle, liposomes Th1/Th17
IC31 TLR9, cationic peptides Th1/Th2
Flagellin TLR5 Ab, Th1/Th2
Imidazoquinolines TLR7/8 Ab, Th1
IMMUNOMODULATORS SIGNALLING THROUGH PRR´S
MPL/GLA
Flagellin
CpG polyIC
Resi- quimod
TDB
SYNTHETIC PAMPS IN VACCINE ADJUVANTS
Olive, Exp. Rev. Vaccine 2012
How can we use cross-talk between PRRs
to achieve:
- Balanced responses (CD4/CD8,
Th1/Th17/Tfh)
- Optimal magnitude, avidity, memory
Synergy/antagony: Is is better to combine
different classes of PAMPS signalling
through different signal pathways
(MYD88/TRIF/SYK)
The distribution of PPR´s: on various APC´s,
in neonates and in different species
(rodent/non-rodents and humans)
FUTURE CHALLENGES AND POSSIBILITIES
How to obtain tissue-specific responses:
- Chemokine receptors
- Vitamins
- Targeted immunisations
FUTURE CHALLENGES AND POSSIBILITIES
How to obtain tissue-specific responses:
Accelerate clinical evaluation of novel adjuvants
IC31, CAF01 and AS01 have been used in phase I trials in Leiden and
Lausanne with H1 and 72f (now M72) respectively, supported by TBVAC
LTK63 have been used in phase I trials, supported by MUVAPRED
FUTURE CHALLENGES AND POSSIBILITIES
How to obtain tissue-specific responses:
- Chemokine receptors
Accelerate clinical evaluation of novel adjuvants
H2H comparison of adjuvants
FUTURE CHALLENGES AND POSSIBILITIES
How to obtain tissue-specific responses:
- Chemokine receptors
Accelerate clinical evaluation of novel adjuvants
H2H comparison of adjuvants
Heterologous prime/boost strategies
FUTURE CHALLENGES AND POSSIBILITIES
How to obtain tissue-specific responses:
- Chemokine receptors
Longevity of responses?
Accelerate clinical evaluation of novel adjuvants
H2H comparison of adjuvants
Heterologous prime/boost strategies
H1:IC PHASE I CLINICAL TRIALS
THYB-01
Ag85B ESAT-6
Phase I - Safety (high endemic, ET)
M.tb. naive / BCG vacc / LTBI
Adults, N=48
Phase I – Safety (low endemic, NL)
Adjuvant dose escelation study
Healthy adults, N=36
THYB-02
Phase I – Safety (low endemic, NL)
BCG vacc / LTBI
Adults, N=36 THYB-03
Vaccine generates long term memory in all phase I trials
FUTURE CHALLENGES AND POSSIBILITIES
How to obtain tissue-specific responses:
- Chemokine receptors
Can potency and inflammation be dissociated
Accelerate clinical evaluation of novel adjuvants
H2H comparison of adjuvants
Heterologous prime/boost strategies
Longevity of responses?
ACKNOWLEDGEMENTS
TB vaccine research
Claus Aagaard
Rolf Billeskov
Truc Thanh Hoang
Joshua Woodworth
Thomas Lindenstrøm
Jacob Munk Hansen
Jonathan Filskov
Niels Peter Knudsen
Iben Sohn
Ahmad Ahmad
Adjuvant research
Dennis Christensen
Karen Korsholm
Jes Dietrich
Signe Tandrup Schmidt
Rasmus Julsgaard Mortensen
Collaborators:
University of Göteborg:
Ali Harandi
IDRI:
Rhea Cöler
Steven Reed
Valneva:
Andreas Meinke
Andreas Fritzer
Novartis:
Cecilia Buonsanti
Ugo D´Oro
LUMC:
Tom Ottenhoff
Simone Joosten
Vaccine development
Ingrid Kromann
Charlotte Green Jensen
Kirsten Bisgaard-Frandtzen
Peter Bang
Birgit Thierry-Carstensen
Lars Vibe Andreasen
Vice president, R & D
Peter L. Andersen