The MCC vaccine program in the UK has dramatically reduced MenC disease rates since its introduction. While protection wanes over time, herd immunity from reduced carriage in teenagers has sustained impact. To maintain control, the schedule is being updated to boost teenagers and address waning immunity. A booster will be added in year 10, and broader quadrivalent vaccines may be considered for this dose.

1. Current issues with
meningococcal vaccine
programmes in the UK
Dr Mary Ramsay, Head of Immunisation, Public Health England

2. Meningococcal serogroup C (MCC)
conjugate vaccination in the UK
In 1999, in response to increase in
serogroup C meningococcal disease
•
the UK was first country to introduce conjugate vaccine
for meningococcal disease
Incidence too low to undertake efficacy trials
•
•
Licensed on the basis of protective levels of serum
bactericidal antibodies that were superior to plain
polysaccharide vaccine
Evidence of immunological memory
Vaccine used following the model of Hib
Miller E, Salisbury D, Ramsay M. Vaccine 2001;20 Suppl 1:S58-67.

3. Group C infections by age
Isolates referred to PHLS, 1998/9
120
100
80
60
40
20
0
<1 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24

4. MCC vaccine implementation
in the UK
Vaccine given with the routine schedule at 2, 3 and 4
months of age
• Coverage of >90% rapidly achieved
Based on pre-vaccine epidemiology, catch-up for all
children <18 years of age completed in 2000
• Coverage exceeded 85% in all cohorts up to 16 years
Immediate dramatic impact on disease rates
• Impact now sustained for over 10 years
• Less than 30 cases reported each year (many in
unvaccinated adults not raised in the UK)

5. Incidence of IMD and serogroup C cases
England and Wales, 1998/99-2011/12
1,000
cases
800
6
Serogroup C
all meningococcal disease
5
4
600
3
400
2
200
1
0
0
incidence /100,000
1,200

6. Vaccine effectiveness by time since
routine infant vaccine
Time since
vaccination
VE (%)
95% confidence
interval
Within a year
96.7%
(88.6%,99.1%)
12-23 months
71.2%
(-1150%,95.9%)
24-35 month
75.3%
(-998%,96.7%)
36+ months
48.7%
(-2025%,91.8%)

7. Evidence of herd immunity
Incidence per 105 in 15-17 year olds
cases/100,000 persons
9
8
Pre-vaccine
65% reduction in rate in
unvaccinated cohort 2000/01
83% reduction in rate in
unvaccinated cohort 2002/03
7
6
5
4
unvaccinated
3
2
vaccinated
1
0
98/99
Ramsay ME et al. BMJ. 2003;326:365-6.
00/01
00/01

8. Nasopharyngeal carriage rates of serogroup
C Neisseria meningitidis, UK adolescents
3.00%
2.50%
2.00%
-71%
-81%
1.50%
1.00%
0.50%
0.00%
1999
Maiden MC et al. J Infect Dis. 2008;197:737-43.
2000
2001

9. Summary of MCC impact
Despite declining protection, major reduction in
MenC incidence and deaths
• Assumption of long term protection was wrong
Main reason for dramatic and sustained impact was
indirect (herd) protection
• Due to decline in carriage rates in teenagers covered by
catch-up programme
Catch-up programme covering all ages to 18 years
vital for control of meningococcal disease
How can we sustain long term control?

10. Meningococcal serogroup C seroprevalence
by age, 1996-9, 2000-4, and 2009
1996-99
100
90
% with SBA titre >=8
80
70
60
50
40
30
20
10
0
2000-2004
2009

11. Results of seroprevalence studies
Antibody response in infants and in catch up programme
was strongly related to age
Antibody levels in those vaccinated below 5 years of age
have declined
Booster dose added to routine schedule at 12 months
•
Meningococcal SBA decay pattern post booster is very similar to
that post primary vaccination*
By 2009, major immunity gap in children aged 1-14 years
BUT, models predict no resurgence of disease for several
years
* Borrow R et al. Clin Vaccine Immunol. 2010;17:154-9.

12. Eligibility and coverage of MenC by vaccination in NHS, 2014
Adult
catch up
< 25%
Sixth form
catch up
Secondary school
catch up
65-74%
83-88%
Primary school
catch up
85-88%
GP Pre-school
catch-up
77%
Toddler
catch-up
85%
Routine MenC
3 dose
>90%
Routine MenC
2+1 or 3+1 doses
>90%
Age in 2014
1-9
years
10-14
years
15
years
16-19
years
20-26
years
27-31
years
32-33
years
34-39
years
Year of Birth 2005-2013 2000-2004 1999 1995-1998 1988-1994 1983-1987 1981-1982 1975-1980
Teenage booster

13. Rationale for new schedule
• Need to balance short term protection in infants with long
term disease control
-
MenC protection in infancy can be achieved with single dose of
some vaccines
Toddler booster response excellent but not long term
• Control is being maintained by high levels of antibody in
school age and adult catch-up cohorts
-
Sustaining indirect protection will require boosting in older children
• Booster to be introduced in year 10 during 13-14
academic year
- University catch-up for older children from 2014-15

14. Eligibility and coverage of MenC by vaccination in NHS, 2014
Adult
catch up
< 25%
Sixth form
catch up
Secondary school
catch up
65-74%
83-88%
Primary school
catch up
85-88%
GP Pre-school
catch-up
77%
Toddler
catch-up
85%
Routine MenC
3 dose
>90%
Routine MenC
2+1 or 3+1 doses
>90%
Age in 2014
1-9
years
10-14
years
15
years
16-19
years
20-26
years
27-31
years
32-33
years
34-39
years
Year of Birth 2005-2013 2000-2004 1999 1995-1998 1988-1994 1983-1987 1981-1982 1975-1980
Teenage booster 2014
University catch-up

15. Which vaccines should the UK use for
the new MenC schedule?
• Not all conjugates are the same
•
Based on experience so far would prefer to use the
most immunogenic vaccines
• Infant protection with a single dose of MenC is
only sufficient with two vaccines
•
•
Menjugate / NeisVac C are preferred
Meningitec in infancy would require two doses
• Toddler booster response is combined with Hib
•
Is also affected by choice of priming vaccine, but high
levels are usually achieved

16. Which vaccines should the UK use for
the new MenC schedule?
• Response to teenage boosters likely to be good
with any MenC containing vaccine
•
Potential to use multivalent vaccine
• Three quadrivalent vaccines now available
•
•
•
Menveo (Novartis) CRM197 conjugate (licensed)
Neimenrix (GSK) Tetanus conjugate
Menactra (SPMSD) Diphtheria conjugate
• Recent study completed in 16-19 year olds with
Menveo and Neimenrix
•
Both vaccines provided protection for ≥98% of
adolescents against all four serotypes

17. Non-B Meningococcal cases by year
(2006/7-2011/12, England & Wales)
100
Number of Cases
C
W135
Y
Other
80
60
40
20
0
2006/2007 2007/2008 2008/2009 2009/2010 2010/2011 2011/2012
Epidemiological Year

18. Conclusions
Conjugate vaccination against MenC has been hugely
successful
For continued control probable need high antibody levels in
the age group where carriage occurs
•
Important to vaccinate adolescents
The 1 + 1 + 1 schedule is likely to be both effective and
efficient
Use of broader vaccines in teenagers will boost MenC
antibody and have potential to prevent other serogroups
•
unlikely to be justifiable unless cost neutral or incidence of these
increase