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Gaps in knowledge of RSV Louis Bont

Lecture Louis Bont_World Vaccine Conference Washington_2015

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Page 1: Lecture Louis Bont_World Vaccine Conference Washington_2015

Gaps in knowledge of RSV

Louis Bont

Page 2: Lecture Louis Bont_World Vaccine Conference Washington_2015

ReSViNET: a Clinical RSV Research Network

• A global network of experts in RSV infections and clinical trial infrastructure

• Vision: combine expertise and leadership to decrease the global burden of RSV infection.

• Mission: perform high quality research to improve knowledge of RSV epidemiology, and to develop safe and effective therapeutic and preventive interventions.

1st ANNUAL RSV EXPERT MEETING JANUARY 2015

ORGANISED BY ReSViNET

2014

2015

Page 3: Lecture Louis Bont_World Vaccine Conference Washington_2015

Outline

1. Morbidity and Mortality

2. Timing of Vaccination

3. RSV, Wheeze and Asthma

Page 4: Lecture Louis Bont_World Vaccine Conference Washington_2015

RSV Epidemiology

• 34,000,000 Patients • 3,400,000 Hospitalizations • 253,000 Deaths

Page 5: Lecture Louis Bont_World Vaccine Conference Washington_2015

Pipeline RSV: Vaccines Overview

Page 6: Lecture Louis Bont_World Vaccine Conference Washington_2015

Can we prevent RSV mortality?

Schickli J Clin Invest 2015

McLellan, Science 2013

Corti Nature 2013

Page 7: Lecture Louis Bont_World Vaccine Conference Washington_2015

What is the peak age of RSV mortality?

[email protected]

Chu JID 2014 Bont PIDJ 2011

Page 8: Lecture Louis Bont_World Vaccine Conference Washington_2015

Prevention ICU admisions

[email protected]

• Multicenter ICU study (n=250)

• Healthy term

• Co- morbidity

• Prematurity

• Protection (hypothetical)

• 30 / 60 / 90 / 120 days

• Proportion prevented (%) 0

102030405060708090

100

30 60 90 120P

reve

nta

ble

Pts

(%

)

Duration of Protection (days)

Co-morbidity

0102030405060708090

100

30 60 90 120

Pre

ven

tab

le P

ts (

%)

Duration of Protection (days)

Healthy Term

Scheltema, in progress

Page 9: Lecture Louis Bont_World Vaccine Conference Washington_2015

Three Distinct Wheezing Phenotypes

RSV Infants wheeze Asthma

Stein Lancet 1999

Sigurs Thorax 2010

Bacharier JACI 2013

Page 10: Lecture Louis Bont_World Vaccine Conference Washington_2015

RSV and Asthma

RSV Bronchiolitis in Early Life (RBEL), n=206, < 13 months

Asthma < 7y 48%

Active asthma 35%

Bacharier, JACI 2013

Page 11: Lecture Louis Bont_World Vaccine Conference Washington_2015

Key Facts on Asthma

Unmet Need

Opportunity Risk

One of the major non-communicable diseases 235 million people currently suffer from asthma Common disease among children. Most asthma-related deaths occur in LMIC

Disability adjusted life years

Page 12: Lecture Louis Bont_World Vaccine Conference Washington_2015

Key Facts on Asthma

Unmet Need

Opportunity Risk

Costs in the United States “The annual direct health care cost of asthma is approximately $50.1 billion; indirect costs

(e.g. lost productivity) add another $5.9 billion, for a total of $56 billion dollars”

Page 14: Lecture Louis Bont_World Vaccine Conference Washington_2015

Chicken or Egg

Blanken NEJM 2013

Serial hypothesis Parallel hypothesis

Pre-existent healthy

Viral bronchiolitis

Recurrent wheeze

Pre-existent susceptibility

Viral

bronchiolitis

Recurrent

wheeze x

x

Page 15: Lecture Louis Bont_World Vaccine Conference Washington_2015

RSV and Wheeze

0

500

1000

1500

2000

2500

1 2 3 4 5 6 7 8 9 10 11 12

Cum

ula

tive w

heezin

g d

ays

Month follow-up

PalivizumabPlacebo

p<0.0001

Blanken NEJM 2013

Page 16: Lecture Louis Bont_World Vaccine Conference Washington_2015

Studying Long-term effects

1. Clinical Relevance (Quality of Life)

2. Societal Relevance (56 billion$)

3. Mechanism of Disease (parallel vs serial hypothesis)

4. Feasibility (small sample size)

Page 17: Lecture Louis Bont_World Vaccine Conference Washington_2015

Conclusions

1. Morbidity and Mortality

2. Timing of Vaccination

3. RSV, Asthma and Wheeze 0

500

1000

1500

2000

2500

1 2 3 4 5 6 7 8 9 10 11 12

Cu

mu

lative w

he

ezin

g d

ays

Month follow-up

PalivizumabPlacebo

Page 18: Lecture Louis Bont_World Vaccine Conference Washington_2015

Save The Date To Meet RSV Experts

DATE 19-21 JANUARY 2016 LOCATION THE NETHERLANDS WEBSITE www.resvinet.org

Page 19: Lecture Louis Bont_World Vaccine Conference Washington_2015

CONTACT ReSViNET Louis Bont (ReSViNET Chairman ) [email protected] +31 (0) 88 75 75 114

Leyla Kragten-Tabatabaie (Network Manager)

[email protected] +31 (0) 611 33 13 91

Cyrus Park (Manager Clinical Research & Development)

[email protected] +31 (0) 621 16 29 69