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

Read, Robert C.; Baxter, David; Chadwick, David R.; Faust, Saul N.; Finn, Adam; Gordon, Stephen B.; Heath, Paul T.; Lewis, David J.M.; Pollard, Andrew J.; Turner, David P.J.; Bazaz, Rohit; Ganguli, Amitava; Havelock, Tom; Neil, Keith R.; Okike, Ifeanyichukwu O; Morales-Aza, Begonia; Patel, Kamlesh; Snape, Matthew D; Williams, John; Gilchrist, Stephanie; Gray, Steve J; Maiden, Martin C J; Toneatto, Daniela; Wang, Huajun; McCarthy, Maggie; Dull, Peter M; Borrow, Ray

Abstract

Background: Meningococcal conjugate vaccines protect individuals directly, but also confer herd protection by interrupting carriage transmission. This Phase III observer-blind, randomised, controlled study evaluated the effects of meningococcal quadrivalent (ACWY) glycoconjugate (MenACWY-CRM) or serogroup B (4CMenB) vaccination on meningococcal carriage rates in young adults.
Methods: University students (aged 18–24 years) from ten sites in England were randomised to receive two vaccinations one month apart: two doses of Japanese Encephalitis vaccine (controls), two doses of 4CMenB (4CMenB), or one dose of MenACWY-CRM then placebo (MenACWY-CRM). Meningococci were isolated from oropharyngeal swabs collected before vaccination and at five scheduled intervals over one year. Primary analysis was cross-sectional carriage one month after the vaccine course; secondary analyses included comparison of carriage at any time point after primary analysis until study termination.
Findings: 2954 subjects were randomised (control, n=987; 4CMenB, n=988; MenACWY-CRM, n=979); approximately one-third of each group was positive for meningococcal carriage at study entry. By one month, there was no significant difference in carriage between controls and 4CMenB (Odds Ratios (OR) [95% CI]; 1·2 [0·8−1·7]) or MenACWY-CRM (OR [95% CI], 0·9 [0·6–1·3]) groups. From three months after dose two, 4CMenB vaccination resulted in significantly lower carriage of any meningococcal strain (calculated efficacy 18·2% [95% CI: 3·4–30·8]) and capsular groups BCWY (calculated efficacy 26·6% [95% CI: 10·5–39·9]) compared to control vaccination. Significantly lower carriage rates were also observed in the MenACWY-CRM group compared with controls: calculated efficacies 39·0% [95%CI: 17·3-55·0] and 36.2% [95%CI: 15·6-51·7] for serogroups Y and CWY, respectively.
Interpretation: MenACWY-CRM and 4CMenB vaccines reduced meningococcal carriage rates over 12 months post-vaccination and, therefore, may affect transmission where widely implemented.

Citation

Read, R. 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., Neil, K. R., Okike, I. O., Morales-Aza, B., Patel, K., Snape, M. D., Williams, J., Gilchrist, S., …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. https://doi.org/10.1016/S0140-6736%2814%2960842-4

• Journal Article Type: Article
• Acceptance Date: Aug 18, 2014
• Online Publication Date: Aug 18, 2014
• Publication Date: Dec 13, 2014
• Deposit Date: Jun 20, 2016
• Publicly Available Date: Jun 20, 2016
• Journal: The Lancet
• Print ISSN: 0140-6736
• Electronic ISSN: 1474-547X
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 384
• Issue: 9960
• Pages: 2123-2131
• DOI: https://doi.org/10.1016/S0140-6736%2814%2960842-4
• Keywords: Meningococcal, carriage, vaccine, serogroup B, conjugate, herd protection
• Public URL: https://nottingham-repository.worktribe.com/output/740920
• Publisher URL: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(14)60842-4/fulltext
• Contract Date: Jun 20, 2016