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Rappuoli slide scienza e industria 27:11:2013rid
This document discusses the potential for vaccines to serve global health and outlines Rino Rappuoli's talk on this topic. It notes that vaccines have allowed people to live longer and have been a paradigm of research in service of global health. New technologies over the last 30 years have made possible vaccines that were previously difficult or impossible. These include conjugate vaccines, reverse vaccinology, adjuvants, and synthetic biology.
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Rappuoli slide scienza e industria 27:11:2013rid
- 1. Vaccini come paradigmadi ricerca al servizio della salute globale Rino Rappuoli Scienza e industria Ricerca e innovazione in biomedicina Università Bocconi, Milano, 27 novembre 2013
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- 5. The unfinished cathedral In Siena, an unfinished cathedral is the largest existing monument to Infectious Diseases, standing reminder of a flourishing economy and culture wiped out forever in just three months by the 1348 PLAGUE
- 6. Smallpox: An Ancientand Deadly Disease Daniel Bernoulli (mathematician and physician; 1700 – 1782) estimated that, in Europe, there were, on average, ca. 600,000 deaths each year from Smallpox. European population ca. 80M Every year 1 person every 140 died from the disease
- 7. Smallpox: An Ancientand Deadly Disease - 1707 36% of Island population died - 1709 14,000 died in Paris - 1753 20,000 died in Paris - 1768 60,000 died in Naples
- 8. Vaccination, the mosteffective medical intervention ever introduced So far saved >700 million disease cases, >150 million deaths 2011-2020 vaccines will save 25 million deaths 2.5 million/year 7000/day 300/hour 5/min WHO Global Action Plan http://www.who.int/immunization/global_vaccine_action_plan/GVAP_doc_2011_2020/en/index.html) 8
- 9. From Jenner toPasteur to Hilleman Isolate Inactivate Inject the microorganism causing disease
- 10. During the last30 years, several new technologies made possible vaccines that were previously impossible
- 11. During the last30 years, several new technologies made possible vaccines that were previously impossible
- 12. Meningococcal disease Caused byNeisseria meningitidis capsular serogroups A, Death B, C, Y, W135 Severe disability Dreaming the olympic games like Pistorius Tragedies covered by media
- 13. During the last30 years, several new technologies made possible vaccines that were previously impossible Conjugate vaccines
- 14. Capsular polysaccharides &Conjugates Haemophilus influenzae type B (Hib) Capsule Pneumococcus Meningococcus Group B streptococcus Capsule Polysaccharide Conjugate
- 15. MenC Conjugate Vaccine(red) Induced high level of Bactericidal Antibodies in Infants. Plain Polysaccharide (blue) was a poor Immunogen
- 16. Conjugate vaccines forMeningococcus C eliminated the disease in the UK Laboratory Confirmed Cases of Serogroup C Meningococcal Disease (England & Wales) Since the introduction of the UK MenC vaccine in 1999 Vaccine >13,000 cases prevented > 1,300 deaths prevented >2,750 permanent sequelae prevented Week No. (totals from mid-year)
- 17. Meningococcus B capsuleis a self antigen and cannot be used for vaccination
- 18. During the last30 years, several new technologies made possible vaccines that were previously impossible Reverse Vaccinology
- 19. Reverse vaccinology a genomicapproach to vaccine discovery Express recombinant proteins 600 potential vaccine candidates identified 350 proteins successfully expressed in E.coli In silico vaccine candidates 91 novel surface-exposed proteins identified 28 novel proteins have bactericidal activity VACCINE CANDIDATES
- 20. 4CMenB Vaccine Composition Three protein antigens (two fusion proteins and one single polypeptide) Outer Membrane Vesicle (OMV) component (NZ PorA is P1.4) LPS PorA OMV Class 4 NadA fHBP NHBA Class 5 PorB 4CMenB is a suspension for injection Dose NHBA- fHbp- GNA1030 GNA2091 NadA OMV 0.5ml 50 µg 50 µg 50 µg 25 µg Al3+ 0.5 mg
- 21. Clinical Development Immunogenicity, Persitance,Concomitant administration, Tolerability Infants and children 2 months to <2 years of age 5850 •5850 received at least 1 dose of BEXSERO •3285 received booster dose in second year of life Children 2 to 10 years of age •250 were included 250 1703 Adolescents and adults ≥11 years of age • 1703 were included *Evaluated in 13 studies including 9 randomized controlled clinical trials.
- 23. MenB Vaccine UKmedia CHMP positive opinion 16 November 2012
- 24. Towards a meningitisfree world The first vaccine lot was released this week Now we can eliminate meningococcal meningitis
- 25. Reverse vaccinology allowedus to target many pathogens that were difficult or impossible before Including SUPERBUGS 4CMenB first genome derived vaccine t!!!! stan s i res ccu c ioti yloco ntib aph A coli ile t S E. fic s . dif mona C o eud Ps !!! GS BU ER UP S Group B Streptococcus Yersinia pestis Group A Streptococcus Chlamydia Malaria
- 26. During the last30 years, several new technologies made possible vaccines that were previously impossible Adjuvants
- 27. MF59: oil-in-water adjuvantlicensed with seasonal trivalent (1997) and pandemic monovalent vaccine Progenitor of other oil-in-water based adjuvants 160nm Oil-in-water emulsion adjuvant licensed for use in seasonal influenza vaccine FLUAD→* since 1997 • More than 200 million oil commercial doses distributed >120 Clinical studies, >200,000 subjects • No safety signals in either Safety MF59 adjuvant emulsion shown also in pregnant women Antigens Pediatric studies and efficacy trial in >3,000 subjects SPAN 85 TWEEN 80 Licensed for 2009 A(H1N1) pandemic vaccine (all ages)
- 28. MF59 increases efficacyof influenza vaccine in children from 43 to 86% cci Va 1.0 ne 59 MF + Vaccine efficacy vs. non-influenza control 0.8 0.6 ci ac V 0.4 ne 0.2 Vaccine also showed satisfactory safety profile: •Increased local reactogenicity •No increase in serious adverse experiences vs. control 0.0 – 0.2 Fluad – 0.4 – 0.6 0 TIV 20 40 60 80 100 120 140 Days post-second dose Vesikari T, et al. NEJM. 160 180 200 220
- 29. During the last30 years, several new technologies made possible vaccines that were previously impossible Synthetic biology Synthetic seeds Self Amplifying Messenger RNA (SAM)
- 30. Influenza, eggs &cell culture time to retire the eggs? TechnoIogy of 1930’s Cell culture, licensed by the FDA in 2012
- 31. A synthetic InfluenzaVaccine Seed in 5 days shipping information instead of viruses
- 32. During the last30 years, several new technologies made possible vaccines that were previously impossible What do we do with all these technologies?
- 33. Vaccines have beendeveloped for children With an aging society, we need a new model for health care R.Rappuoli, C. Mandl, S: Black , E. De Gregorio Nature Reviews Immunology | November 2011; doi:10.1038/nri3085
- 34. Vaccines for everyage R.Rappuoli, C. Mandl, S: Black , E. De Gregorio Nature Reviews Immunology | November 2011; doi:10.1038/nri3085
- 36. Vaccines against poverty AnInstitute 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
- 37. Master Program inVaccinology & Pharmaceutical Clinical Development: •Has reached so far 24 countries of the developing world •70% of the former students are actively working in the vaccinology field •Former students are followed for 5 y
- 38. Jobs, investments, brains 1992 Jobs 2006 2013 234 1100 2000 Investments Investmentsin R&D ------280M---------890M----- People 45% of our collaborators are women 45% are graduated employees 40% are less than 35 years old Collaborators come from 43 different countries