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
• 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
Study MethodsPre-licensure study to assess effect on carriage at an individual level
Primary Analysis at 1 Month After the Vaccination Series
Vaccine GroupsEfficacy %(95% CI)MenACWY-CRM Control
Visit 2[Month 1]
Number 56 58 16.0%
(-27.3 – 44.5)% 5.87% 6.12%
N 954 947
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 GroupsEfficacy %(95% CI)4CMenB Control
Visit 3[Month 2]
Number 87 75 -18.2%
(-73.3 – 19.4)% 9.50% 8.08%
N 916 928
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
*Virulent ST types are those capsular group B ST types (or clonal complex members) causing disease in the UK (2006-2010).
Analyses adjusted for baseline carriage, treatment group, centre and significant risk factors as identified within the multivariate model.
Vaccine GroupsEfficacy %(95% CI)MenACWY-
CRM Control
C, W, YSerogroupable
Number 193 26036.2%
(15.6 – 51.7)% 5.5% 7.4%
N 3520 3504
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)
MenACWY-CRM reduces nasopharyngeal carriage of N. meningitidis serogroup CWY strains
YSerogroupable
Number 157 227
39.0%
(17.3 – 55.0)
% 4.5% 6.5%
N 3520 3504
Analyses adjusted for baseline carriage, treatment group, centre and significant risk factors as identified within the multivariate model.
4CMenB– Carriage at Cumulative Later Sampling Points4CMenB 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)
Any N. meningitidis
Number 797 885
18.2%
(3.4 – 30.8)
% 32.0% 34.4%
N 2489 2576
Vaccine GroupsEfficacy %(95% CI)4CMenB Control
B, C, W, Y Capsular group
Number 449 53926.6%
(10.5 – 39.9)% 18.0% 20.9%
N 2489 2576
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.
• 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.
B, C, W, Y Capsular group Any N. meningitidis
Efficacy %(95% CI)
Efficacy %(95% CI)
Early Enrollers (<30 Days After Start of the Semester)
N=1022 – 1031
32.0%
(8.2 – 49.6)
33.7%
(13.9 – 49.0)
SmokersN=320 – 425
44.8%
(14.0 – 64.5)
32.2%
(2.5 – 52.9)
4CMenB – Exploratory AnalysisRisk Factor Groups With High Transmission/Acquisition4CMenB 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)
Analyses adjusted for baseline carriage, treatment group, centre and significant risk factors as identified within the multivariate model.
• 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
Conclusions
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
10
David BaxterRohit BazazRay BorrowDavid R. ChadwickPeter M. DullSaul N. FaustAdam Finn
Tav GanguliStefanie GilchristStephen GordonSteve J. GrayTom HavelockT. HeathClaudia Kittel
J.M. LewisMaggie McCarthyBegonia Morales-AzaKeith R. NealIfeanyichukwu OkikeKamlesh PatelAndrew J. Pollard
Robert ReadMatthew D. SnapeDavid P.J. TurnerJohn Williams
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