Professor Robert Read's presentation at Meningitis Research Foundation's 2013 conference, Meningitis & Septicaemia in Children & Adults

1. Impact of a Quadrivalent Conjugate
(MenACWY-CRM) or a Serogroup B (4CMenB)
Meningococcal Vaccine on Meningococcal
Carriage in English University Students
Robert C. Read and Colleagues

2. Study Methods
Pre-licensure study to assess effect on carriage at an individual level
• Phase III, multi-centre, RCT
• 2,968 students from universities at 10 different
UK sites
• 3 month enrolment (Sep–Dec 2010)
• Subjects received either:
– 2 doses of 4CMenB (BEXSERO)
– 1 dose of MenACWY-CRM (MENVEO)/1 dose of saline
placebo
– 2 doses of Japanese encephalitis (IXIARO)
(control)
• Nasopharyngeal swabs taken
at baseline, and at Months
1, 2, 4, 6 and 12
• Carriage isolate characterisation performed
at HPA (PHE) and Oxford University

3. Primary Analysis at 1 Month After the Vaccination Series
4CMenB co-primary
Carriage prevalence of virulent sequence types (ST)* of N. meningitidis capsular group B at 1 month following
administration of 2 doses of 4CMenB
Vaccine Groups
4CMenB
Number
87
75
-18.2%
%
9.50%
8.08%
N
Visit 3
[Month 2]
Control
Efficacy %
(95% CI)
916
928
(-73.3 – 19.4)
*Virulent ST types are those capsular group B ST types (or clonal complex members) causing disease in the UK (2006-2010).
MenACWY-CRM co-primary
Carriage prevalence of N. meningitidis combined serogroups A, C, W and Y at 1 month following administration of a
single dose of MenACWY-CRM
Vaccine Groups
MenACWY-CRM
Number
56
58
16.0%
%
5.87%
6.12%
N
Visit 2
[Month 1]
Control
Efficacy %
(95% CI)
954
947
Analyses adjusted for baseline carriage, treatment group, centre and significant risk factors as
identified within the multivariate model.
(-27.3 – 44.5)

4. MenACWY-CRM – Carriage at Cumulative Later
Sampling Points
MenACWY-CRM secondary
Carriage prevalence and calculated efficacy of combined serogroups CWY and serogroup Y across cumulative
later timepoints (Visits 3–6)
Vaccine Groups
MenACWYCRM
Number
C, W, Y
Serogroupable
Control
193
260
%
5.5%
36.2%
7.4%
(15.6 – 51.7)
N
Serogroupable
3520
3504
Number
Y
Efficacy %
(95% CI)
157
227
%
4.5%
39.0%
6.5%
(17.3 – 55.0)
N
3520
3504
MenACWY-CRM reduces nasopharyngeal carriage
of N. meningitidis serogroup CWY strains
Analyses adjusted for baseline carriage, treatment group, centre and significant risk factors as
identified within the multivariate model.

5. 4CMenB– Carriage at Cumulative Later Sampling Points
4CMenB secondary
Carriage prevalence and calculated efficacy for carriage of combined capsular groups BCWY or all N. meningitidis strains
across cumulative later timepoints (Visits 4–6)
Vaccine Groups
4CMenB
Number
539
26.6%
%
18.0%
20.9%
2489
2576
(10.5 – 39.9)
Number
797
885
18.2%
%
32.0%
34.4%
N
Any N.
meningitidis
449
N
B, C, W, Y
Capsular group
Control
Efficacy %
(95% CI)
2489
2576
(3.4 – 30.8)
4CMenB reduces nasopharyngeal carriage of
N. meningitidis capsular group BCWY strains
Non-significant trends for virulent B strains (12.6%; p=0.350) and all ST B strains (15.6%;
p=0.225)
Analyses adjusted for baseline carriage, treatment group, centre and significant risk factors as
identified within the multivariate model.

6. 4CMenB – Exploratory Analysis
Risk Factor Groups With High Transmission/Acquisition
4CMenB secondary
Carriage prevalence and calculated efficacy for carriage of combined capsular groups BCWY or all N. meningitidis strains
across cumulative later timepoints (Visits 4–6)
B, C, W, Y
Capsular group
Efficacy %
(95% CI)
Early Enrollers
(<30 Days After Start of the Semester)
N=1022 – 1031
Smokers
N=320 – 425
Any N. meningitidis
Efficacy %
(95% CI)
32.0%
33.7%
(8.2 – 49.6)
(13.9 – 49.0)
44.8%
32.2%
(14.0 – 64.5)
(2.5 – 52.9)
• In all risk factor groups, although trends were evident for efficacy against
virulent B strains and all ST B strains, statistical significance was not met.
Analyses adjusted for baseline carriage, treatment group, centre and significant risk factors as
identified within the multivariate model.

7. Conclusions
• Primary objectives were not achieved for either MenACWY-CRM or 4CMenB
• MenACWY-CRM: Secondary analyses demonstrated an impact on carriage of CWY
combined
• 4CMenB: Secondary analyses demonstrated an impact on carriage of BCWY combined
and any N. meningitidis
– Effect apparently enhanced among groups at high risk for transmission
– Trends observed in carriage impact and new acquisition of MenB strains
• Overall results support a possible herd impact by both vaccines
• Only post-implementation surveys within large scale vaccination programs will
determine fully the population level impact of these vaccines

8. Acknowledgements
• Clinical Research Facility staff at Sheffield, Liverpool,
Manchester, Middlesbrough, Oxford, Southampton, Bristol, St
George’s, Guildford, Nottingham
• UK National Institute of Health Clinical Research Network
(NIHR CRN)
• Public Health England
• Novartis Vaccines and Diagnostics
David Baxter
Rohit Bazaz
Ray Borrow
David R. Chadwick
Peter M. Dull
Saul N. Faust
Adam Finn
Tav Ganguli
Stefanie Gilchrist
Stephen Gordon
Steve J. Gray
Tom Havelock
T. Heath
Claudia Kittel
J.M. Lewis
Maggie McCarthy
Begonia Morales-Aza
Keith R. Neal
Ifeanyichukwu Okike
Kamlesh Patel
Andrew J. Pollard
Robert Read
Matthew D. Snape
David P.J. Turner
John Williams
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