Dr Andrew Riordan's presentation at Meningitis Research Foundation's 2014 Meningitis Symposium http://www.meningitis.org/symposium2014

1. JCVI recommendation on MenB
vaccine

2. Serogroup B Meningococcus
• Commonest cause of
meningococcal disease in UK
• Similar to antigen on foetal brain
tissue
• Other vaccine targets being
investigated (OMPs)
• A group B vaccine was always
5 years away!

3. Meningococcal Cell Wall

4. MeNZB vaccine
• Epidemic of group B
P1.7-2,4
• Tailor made vesicle
vaccine for <20s
• Effectiveness ~73%
• (against epidemic strain)
Clin Infect Dis 2009;49:597–605
Meningococcal disease in
New Zealand 1970–2007

5. Reverse vaccinology
• Genome of serogroup B
strain used to identify
vaccine candidates
• 350 candidate antigens
expressed
• Identified 7 proteins;
surface exposed,
conserved, induce
bactericidal antibody
response
Science 2000;287:1816-20

6. 4CMenB vaccine
• Neisseria Heparin-Binding antigen (NHBA)
• Neisserial adhesin (NadA)
• Factor H-binding protein (fHbp)
• PorA from MeNZB

7. Men B vaccine;
What do the JCVI want to know?
• Is it effective?
• Is it safe?
• Is it worth it?

8. Invasive meningococcal B
infections, E&W; 1998-2012
0
1000
2000
3000
4000
5000
6000
<1 1-4 5-9 10-14 15-19 20-24 25-29 30-34 >35
Age (Years)

9. Immunogenicity in Infants
• 4CMenB vaccination at 2, 3, and 4 months
with routine vaccines + 12 month booster
• 88 - 99% infants developed hSBA titers ≥1:5
against indicator strains
• Responses to routine vaccines non-inferior
(except pertactin and Pneumo 6B)
JAMA 2012;307:573-82, Lancet 2013;381:825-835

10. Immunogenicity in Infants
Lancet 2013;381:825-835

11. What will 4CMenB cover?
Lancet Infect Dis. 2013 ;13:416-25
Meningococcal antigen typing system (MATS)
78% of European MenB strains would be killed
88% strains (E&W2007-2008)
killed in hSBA assay.
Vaccine 2013; 31: 4968-74.

12. Safety in Infants
• “Most notable systemic reaction was fever”
esp when co-administered with routine imms
• More anti-pyretic use – prophylactic
paracetamol advised
• 4 cases of Kawasaki disease
Lancet 2013;381:825-835

13. DUTY ON THE SECRETARY OF STATE
FOR ENGLAND
• The Health Protection (Vaccination) Regulations 2009
place a duty on the Secretary of State for Health in
England to ensure, so far as is reasonably practicable,
that the recommendations of JCVI are implemented,
where those recommendations:

14. DUTY ON THE SECRETARY OF STATE
FOR ENGLAND
a. New national vaccination programme;
b. made by JCVI;
c. in response to a question by the Secretary of
State;
d. based on an assessment which demonstrates
costeffectiveness;
e. not travel or occupational health vaccines.

15. Cost-effectiveness
Meningococcal vaccines likely to be cost
effective;
• when the incidence of disease is high
• if vaccine gives “indirect protection” (herd
immunity from preventing carriage)

16. Invasive meningococcal
infections, England and Wales
0
500
1,000
1,500
2,000
2,500
3,000
Y
W135
C
B
1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013
Incidence of disease is low

17. Meningococcal carriage by age
Lancet Infect Dis. 2010;10:853-61.
Infants 4•5%
19-year olds 23•7%
50-year olds 7•8%

18. Economic and mathematical
modelling study of potential impact
• Unlikely to be cost-effective in the Netherlands
Hum Vaccin Immunother. 2013;9(5).
• In UK could prevent 27% of cases by vaccinating
infants
• Could prevent 71% case by vaccinating infants
PLUS catch-up campaign, if vaccine protects
against carriage
Vaccine. 2013 Apr 5. pii: S0264-410X(13)00369-1
• Data on 4CMenB preventing carriage in
teenagers - uncertain

19. Interim position statement Men B
July 2013
• “on the basis of the available evidence routine
infant or toddler immunisation is highly
unlikely to be cost effective at any vaccine
price”
• JCVI found assessment challenging
– absence of key data
• JCVI concerned about adverse impact
– large uncertainties
Needs;
- population based evaluation in adolescents;
?carriage effect
- evaluation of infant immunisation in a large
cohort (i.e. The UK)

20. MenB statement March 2014
• A programme providing vaccinations at 2, 4,
and 12 months schedule was likely to be both
effective and cost-effective, albeit at a price
significantly lower price than the list price for
Bexsero®.
• Even in the most favourable of scenarios no
infant programme could demonstrate cost-
effectiveness at the list price for Bexsero®.

21. Recommendation – March 2014
• JCVI recommended a programme for use of
the MenB vaccine at 2, 4, 12 months of age in
a carefully planned programme.
• Plans for implementation should anticipate a
sustainable and cost-effective programme.
• Advised a targeted carriage study in
adolescents to assess the impact on carriage.

22. Men B vaccine;
What do the JCVI want to know?
• Is it effective? – immunogenic
?coverage, ?efficacy
• Is it safe? – fevers, ?Kawasaki
>5000 infants and toddlers
• Is it worth it? – cost effective at low
vaccine price