La vaccinazione Ilfondamento della pratica immunologica Rino - - PowerPoint PPT Presentation

La vaccinazione

Ilfondamento della pratica immunologica

Rino Rappuoli

Firenze

12 Novembre 2016

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Some history of human evolution

55 years gained since 1700 35 years gained since 1900

In 1900 in the USA life was short

In 1900 in the USA people died of infectious diseases

Infectious Diseases

Diphtheria (40million prevented) Measles (35 million prevented) Smallpox ...

Infectious Diseases

Diphtheria (40million prevented) Measles (35 million prevented) Smallpox ...

Non Communicable Diseases

Ischemic Heart Disese Stroke Cancer Diabetes Alzheimer .....

From Jenner to Pasteur to Hilleman

Isolate Inactivate Inject the microorganism causing disease

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

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Conjugate vaccines

Haemophilus influenzae type B (Hib) Pneumococcus Meningococcus Group B streptococcus

Capsular polysaccharides & Conjugates

Capsule

Capsule Polysaccharide Conjugate

MenC Conjugate Vaccine (red) Induced high level of Bactericidal Antibodies in Infants. Plain Polysaccharide (blue) was a poor Immunogen

Meningococcus B capsule is a self antigen and cannot be used for vaccination

Reverse Vaccinology

and a vaccine for Meninigococcus B

In silico vaccine candidates Express recombinant proteins

VACCINE CANDIDATES 600 potential vaccine candidates identified 350 proteins successfully expressed in E.coli 91 novel surface-exposed proteins identified 28 novel proteins have bactericidal activity

Reverse Vaccinology A genomic approach

for a Meningococcus B vaccine

Reverse Vaccinology

Craig Venter

(May 11, 2001)

MenB, first vaccine to receive breakthrough therapy designation by FDA Princeton, USA London, UK

Since september 1st 2015 all newborns in the UK are vaccinated with MenB vaccine

• 43,740 people vaccinated between May 5 and 17 June 2014
• 12,332 followed with active surveillance
• 14-15 % fever in less than 2 years (less than expected but high use of antipyretics )
• 2 convulsions (6 expected)
• 99% willing to receive 2nd dose
• Active surveillance has not identified any severe problem and confirmed significant frequency of local pain, fever (less than expected) and general malaise.

Seguenay-Lac-Saint-Jean, 2014

Vaccination of the entire population from 2 months to 20 years of age

De Serres et al, BIBLIOTHEQUE ET ARCHIVES NATIONALES DU QUEBEC, LIBRARY AND ARCHIVES CANADA . ISBN: 978-2-550-71345-6 (FRENCH PDF),

ISBN: 978-2-550-71653-2 (PDF), c Gouvernement du Quebec (2014) , http://www.inspq.qc.ca. Presentation by G. De Serres, at Feb 2016 ACIP

meeting.

no invasive menB cases observed among the 47,115 vaccinated ages 2 mos-20 years, crude VE=100%

Real efficacy from the field

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83% effectiveness and 94% efficacy during the

first 10 months in the UK

The largest petition ever in the UK is for MenB vaccination (before Brexit)

• More than 820 000 people have backed a

campaign for all children up to the age of 11 years to receive GlaxoSmithKline’s Bexsero, which is currently

used as part of routine vaccination for babies born since May 1, 2015, with doses at 2 months, 4 months, and a booster at 12 months.

– The Lancet Infectious Diseases 16, pg 385, April 2016

Faye’s story

Towards a meningitis free world

Now we can eliminate meningococcal meningitis

Reverse Vaccinology can also provide vaccines for Antibiotic Resistant bacteria (superbugs!!!) Staphylococcus

• E. coli
• C. difficile

Pseudomonas Group A Streptococcus

Reverse Vaccinology 2.0: human immunology instructs vaccine antigen design

Rappuoli, Bottomley, D’Oro, Finco, De Gregorio JEM April 2016

Structural Vaccinology Structure-based antigen design

Pre-fusion Post-fusion

Structural Vaccinology

the RSV example

• Vectors
• Synthetic seeds
• Self Amplifying

Messenger RNA (SAM)

Synthetic biology

Viral vectors

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Ebola Ebola

Adjuvants

Fluad TIV

– 0.6 – 0.4 – 0.2 0.0 0.2 0.4 0.6 0.8 1.0

Vaccine efficacy

• vs. non-influenza control

20 40 60 80 100 120 140 160 180 200 220

Days post-second dose Vesikari T, et al. NEJM.

MF59 increases efficacy of influenza vaccine in children from 43 to 86%

Vaccine also showed satisfactory safety profile:

• Increased local reactogenicity
• No increase in serious adverse

experiences vs. control V a c c i n e + M F 5 9 V a c c i n e

MF59 adjuvant emulsion

• il

SPAN

85

TWEEN 80

Antigens

160nm

First Malaria vaccine licensed

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Ebola vaccine 100% efficacy Zoster vaccine 97% efficacy in the elderly

Three breakthrough vaccines in 2015

Vaccines continue to serve our society

AS01 adjuvant AS01 adjuvant VSV Viral vector

How can these technologies help

• ur society?

Vaccines can do more for our society

R.Rappuoli, C. Mandl, S: Black , E. De Gregorio Nature Reviews Immunology | November 2011; doi:10.1038/nri3085

Great job!

Vaccines can do more for our society

R.Rappuoli, C. Mandl, S: Black , E. De Gregorio Nature Reviews Immunology | November 2011; doi:10.1038/nri3085

N e x t t a r g e t !

Vaccines can do more for our society

R.Rappuoli, C. Mandl, S: Black , E. De Gregorio Nature Reviews Immunology | November 2011; doi:10.1038/nri3085

Great job! N e x t t a r g e t !

Vaccines for today’s society

In low income countries life is still very short

In poor countries people die from Infectious Diseases Vaccines can make a big difference

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)

New name: GSK Vaccine Institute for Global Health (GVGH)

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

• Shighella vaccine Phase I 2014

The Grand Convergence

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To close the health gap between poor and rich countries