Vaccines of the future

Transcription

1 Vaccines of the future Rino Rappuoli Conference on New Horizons for Vaccine Research and Innovation Session on Innovation on Vaccine Design Bruxelles, March

2 Vaccination, the most effective medical intervention ever introduced So far saved >700 million disease cases, >150 million deaths vaccines will save 25 million deaths 2.5 million/year 7000/day 300/hour 5/min

3 From Jenner to Pasteur to Hilleman Isolate Inactivate Inject the microorganism causing disease

4 During the last 30 years, several new technologies made possible vaccines that were previously impossible

5 Today we see an explosion of new technologies 2014

6 Conjugate vaccines

7 Capsular polysaccharides & Conjugates Haemophilus influenzae type B (Hib) Capsule Pneumococcus Capsule Meningococcus Polysaccharide Group B streptococcus Conjugate

8 Reverse Vaccinology

9 Reverse Vaccinology A genomic approach to vaccine discovery In silico vaccine candidates Express recombinant proteins 600 potential vaccine candidates identified 350 proteins successfully expressed in E.coli 91 novel surface-exposed proteins identified 28 novel proteins have bactericidal activity VACCINE CANDIDATES

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11 Bexsero in Princeton

12 Reverse vaccinology allowed us to target many pathogens that were difficult or impossible before Including SUPERBUGS MenB first genome derived vaccine Malaria Group B Streptococcus Group A Streptococcus Yersinia pestis Chlamydia

13 Adjuvants

14 Vaccine efficacy vs. non-influenza control MF59 increases efficacy of influenza vaccine in children from 43 to 86% Fluad TIV Days post-second dose Vaccine also showed satisfactory safety profile: Increased local reactogenicity No increase in serious adverse experiences vs. control Vesikari T, et al. NEJM.

15 pg/ml pg/ml pg/ml pg/ml pg/ml pg/ml pg/ml pg/ml Comparative immunogenicity testing of ADITEC adjuvants: Transcriptomics analysis of ADITEC adjuvants CAF CAF CAF01 CAF IFN-y IL-5 IL-17 IL-2 IC IFN-y IL-5 IL-17 IL-2 IC IFN-y IL-5 IL-17 IL-2 IC31 6h 30% 70% IFN-y IL-5 IL-17 IL-2 0 IFN-y IL-5 IL-17 IL-2 0 IFN-y IL-5 IL-17 IL MF MF MF59 24h 25% 75% 95% 5% IFN-y IL-5 IL-17 IL-2 0 IFN-y IL-5 IL-17 IL-2 0 IFN-y IL-5 IL-17 IL GLA-SE GLA-SE GLA-SE 72h 70% 30% 54% 46% IFN-y IL-5 IL-17 IL-2 0 IFN-y IL-5 IL-17 IL-2 0 IFN-y IL-5 IL-17 IL-2 H56 Tuberculosis MOMP Chlamydia Hemagglutinin

16 Structural Vaccinology Structure-based antigen design

17 Structural Vaccinology the RSV example Pre-fusion Post-fusion

18 Synthetic biology Synthetic seeds Self Amplifying Messenger RNA (SAM)

19 A synthetic Influenza Vaccine Seed in 5 days shipping information instead of viruses

20 Systems biology

21 Systems biology From 10,000 people with 10 data each to 10 people with 10,000 data each

22 ADITEC: 13 Clinical Studies

23 Can these technologies help the aging society?

24 Vaccines for every age R.Rappuoli, C. Mandl, S: Black, E. De Gregorio Nature Reviews Immunology November 2011; doi: /nri3085

25 Vaccines for today s society

26 Vaccines against poverty An Institute to address the gaps in vaccine development In the recent past, no mechanism was in place to develop vaccines needed only in developing countries Novartis Vaccines Institute for Global Health (NVGH) A new non-profit initiative to develop effective and affordable vaccines for neglected infectious diseases of developing countries Located in Siena, Italy Legal entity started in Feb 2007 Allan Saul hired as CEO Sept 2007 Inauguration Feb 22, 2008 Typhoid vaccine licensed to BioE post phase II, June 2013

27 Which organization for vaccine development?

28 Maurice Hillemann One man, nine vaccines, that practically every child gets

29 Collaboration of many partners is necessary for a vaccine development (Big science)

30 challenges for vaccine development

31 Fatigue, misperceptions, failure to assign the right value to vaccines Fatigue Immunization typically prevents diseases, which have been nearly eradicated, so most people lack first-hand experience 2012 Vaccine value in a world of limited resources cost effectiveness becomes important in decision making Health economics not able to assign the right value to vaccines SMART VACCINES 2013 Saving money or saving lives? Should industry invest in vaccines?

32 Institute of Medicine (IOM) initiative SMART Vaccines 28 attributes 8 categories From Cost/QALY To Cost/QALY + 27 attributes Strategic Multi-Attribute Ranking- Toll (SMART) Vaccines