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Effect of a quadrivalent meningococcal ACWY glycoconjugate or a serogroup B meningococcal vaccine on meningococcal carriage: an observer-blind, phase 3 randomised clinical trial

Effect of a quadrivalent meningococcal ACWY glycoconjugate or a serogroup B meningococcal vaccine on meningococcal carriage: an observer-blind, phase 3 randomised clinical trial
Effect of a quadrivalent meningococcal ACWY glycoconjugate or a serogroup B meningococcal vaccine on meningococcal carriage: an observer-blind, phase 3 randomised clinical trial
BACKGROUND:
Meningococcal conjugate vaccines protect individuals directly, but can also confer herd protection by interrupting carriage transmission. We assessed the effects of meningococcal quadrivalent glycoconjugate (MenACWY-CRM) or serogroup B (4CMenB) vaccination on meningococcal carriage rates in 18-24-year-olds.

METHODS:
In this phase 3, observer-blind, randomised controlled trial, university students aged 18-24 years from ten sites in England were randomly assigned (1:1:1, block size of three) to receive two doses 1 month apart of Japanese Encephalitis vaccine (controls), 4CMenB, or one dose of MenACWY-CRM then placebo. Participants were randomised with a validated computer-generated random allocation list. Participants and outcome-assessors were masked to the treatment group. Meningococci were isolated from oropharyngeal swabs collected before vaccination and at five scheduled intervals over 1 year. Primary outcomes were cross-sectional carriage 1 month after each vaccine course. Secondary outcomes included comparisons of carriage at any timepoint after primary analysis until study termination. Reactogenicity and adverse events were monitored throughout the study. Analysis was done on the modified intention-to-treat population, which included all enrolled participants who received a study vaccination and provided at least one assessable swab after baseline. This trial is registered with ClinicalTrials.gov, registration number NCT01214850.

FINDINGS:
Between Sept 21 and Dec 21, 2010, 2954 participants were randomly assigned (987 assigned to control [984 analysed], 979 assigned to 4CMenB [974 analysed], 988 assigned to MenACWY-CRM [983 analysed]); 33% of the 4CMenB group, 34% of the MenACWY-CRM group, and 31% of the control group were positive for meningococcal carriage at study entry. By 1 month, there was no significant difference in carriage between controls and 4CMenB (odds ratio 1·2, 95% CI 0·8-1·7) or MenACWY-CRM (0·9, [0·6-1·3]) groups. From 3 months after dose two, 4CMenB vaccination resulted in significantly lower carriage of any meningococcal strain (18·2% [95% CI 3·4-30·8] carriage reduction), capsular groups BCWY (26·6% [10·5-39·9] carriage reduction), capsular groups CWY (29·6% [8·1-46·0] carriage reduction), and serogroups CWY (28·5% [2·8-47·5] carriage reduction) compared with control vaccination. Significantly lower carriage rates were also noted in the MenACWY-CRM group compared with controls: 39·0% (95% CI 17·3-55·0) carriage reduction for serogroup Y and 36·2% (15·6-51·7) carriage reduction for serogroup CWY. Study vaccines were generally well tolerated, with increased rates of transient local injection pain and myalgia in the 4CMenB group. No safety concerns were identified.

INTERPRETATION:
Although we detected no significant difference between groups at 1 month after vaccine course, MenACWY-CRM and 4CMenB vaccines reduced meningococcal carriage rates during 12 months after vaccination and therefore might affect transmission when widely implemented.
0140-6736
2123-2131
Read, Robert C.
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Baxter, D.
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Chadwick, D.R
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Faust, S.N.
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Finn, A.
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Gordon, S.B.
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Heath, P.T.
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Lewis, D.J.
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Pollard, A.J.
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Turner, D.P.
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Bazaz, R.
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Ganguli, A.
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Havelock, T.
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Neal, K.R.
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Okike, I.O.
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Morales-Aza, B.
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Patel, K.
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Snape, M.D.
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Williams, J.
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Gilchrist, S.
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Maiden, M.C.
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Toneatto, D.
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Wang, H.
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McCarthy, M.
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Dull, P.M.
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Borrow, R.
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Read, Robert C.
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Baxter, D.
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Chadwick, D.R
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Faust, S.N.
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Finn, A.
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Gordon, S.B.
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Heath, P.T.
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Lewis, D.J.
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Pollard, A.J.
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Turner, D.P.
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Bazaz, R.
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Ganguli, A.
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Havelock, T.
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Neal, K.R.
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Okike, I.O.
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Morales-Aza, B.
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Patel, K.
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Snape, M.D.
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Williams, J.
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Gilchrist, S.
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Maiden, M.C.
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Toneatto, D.
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Wang, H.
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McCarthy, M.
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Dull, P.M.
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Borrow, R.
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Read, Robert C., Baxter, D., Chadwick, D.R, Faust, S.N., Finn, A., Gordon, S.B., Heath, P.T., Lewis, D.J., Pollard, A.J., Turner, D.P., Bazaz, R., Ganguli, A., Havelock, T., Neal, K.R., Okike, I.O., Morales-Aza, B., Patel, K., Snape, M.D., Williams, J., Gilchrist, S., Maiden, M.C., Toneatto, D., Wang, H., McCarthy, M., Dull, P.M. and Borrow, R. (2014) Effect of a quadrivalent meningococcal ACWY glycoconjugate or a serogroup B meningococcal vaccine on meningococcal carriage: an observer-blind, phase 3 randomised clinical trial. Lancet, 384 (9960), 2123-2131. (doi:10.1016/S0140-6736(14)60842-4). (PMID:25145775)

Record type: Article

Abstract

BACKGROUND:
Meningococcal conjugate vaccines protect individuals directly, but can also confer herd protection by interrupting carriage transmission. We assessed the effects of meningococcal quadrivalent glycoconjugate (MenACWY-CRM) or serogroup B (4CMenB) vaccination on meningococcal carriage rates in 18-24-year-olds.

METHODS:
In this phase 3, observer-blind, randomised controlled trial, university students aged 18-24 years from ten sites in England were randomly assigned (1:1:1, block size of three) to receive two doses 1 month apart of Japanese Encephalitis vaccine (controls), 4CMenB, or one dose of MenACWY-CRM then placebo. Participants were randomised with a validated computer-generated random allocation list. Participants and outcome-assessors were masked to the treatment group. Meningococci were isolated from oropharyngeal swabs collected before vaccination and at five scheduled intervals over 1 year. Primary outcomes were cross-sectional carriage 1 month after each vaccine course. Secondary outcomes included comparisons of carriage at any timepoint after primary analysis until study termination. Reactogenicity and adverse events were monitored throughout the study. Analysis was done on the modified intention-to-treat population, which included all enrolled participants who received a study vaccination and provided at least one assessable swab after baseline. This trial is registered with ClinicalTrials.gov, registration number NCT01214850.

FINDINGS:
Between Sept 21 and Dec 21, 2010, 2954 participants were randomly assigned (987 assigned to control [984 analysed], 979 assigned to 4CMenB [974 analysed], 988 assigned to MenACWY-CRM [983 analysed]); 33% of the 4CMenB group, 34% of the MenACWY-CRM group, and 31% of the control group were positive for meningococcal carriage at study entry. By 1 month, there was no significant difference in carriage between controls and 4CMenB (odds ratio 1·2, 95% CI 0·8-1·7) or MenACWY-CRM (0·9, [0·6-1·3]) groups. From 3 months after dose two, 4CMenB vaccination resulted in significantly lower carriage of any meningococcal strain (18·2% [95% CI 3·4-30·8] carriage reduction), capsular groups BCWY (26·6% [10·5-39·9] carriage reduction), capsular groups CWY (29·6% [8·1-46·0] carriage reduction), and serogroups CWY (28·5% [2·8-47·5] carriage reduction) compared with control vaccination. Significantly lower carriage rates were also noted in the MenACWY-CRM group compared with controls: 39·0% (95% CI 17·3-55·0) carriage reduction for serogroup Y and 36·2% (15·6-51·7) carriage reduction for serogroup CWY. Study vaccines were generally well tolerated, with increased rates of transient local injection pain and myalgia in the 4CMenB group. No safety concerns were identified.

INTERPRETATION:
Although we detected no significant difference between groups at 1 month after vaccine course, MenACWY-CRM and 4CMenB vaccines reduced meningococcal carriage rates during 12 months after vaccination and therefore might affect transmission when widely implemented.

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e-pub ahead of print date: 18 August 2014
Organisations: Faculty of Medicine

Identifiers

Local EPrints ID: 371835
URI: http://eprints.soton.ac.uk/id/eprint/371835
ISSN: 0140-6736
PURE UUID: b57b9059-a32d-4cef-bc53-5ef63a93244e
ORCID for Robert C. Read: ORCID iD orcid.org/0000-0002-4297-6728
ORCID for S.N. Faust: ORCID iD orcid.org/0000-0003-3410-7642

Catalogue record

Date deposited: 18 Nov 2014 14:55
Last modified: 20 Feb 2021 02:43

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Contributors

Author: Robert C. Read ORCID iD
Author: D. Baxter
Author: D.R Chadwick
Author: S.N. Faust ORCID iD
Author: A. Finn
Author: S.B. Gordon
Author: P.T. Heath
Author: D.J. Lewis
Author: A.J. Pollard
Author: D.P. Turner
Author: R. Bazaz
Author: A. Ganguli
Author: T. Havelock
Author: K.R. Neal
Author: I.O. Okike
Author: B. Morales-Aza
Author: K. Patel
Author: M.D. Snape
Author: J. Williams
Author: S. Gilchrist
Author: M.C. Maiden
Author: D. Toneatto
Author: H. Wang
Author: M. McCarthy
Author: P.M. Dull
Author: R. Borrow

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