ArticlesEffect of a quadrivalent meningococcal ACWY glycoconjugate or a serogroup B meningococcal vaccine on meningococcal carriage: an observer-blind, phase 3 randomised clinical trial
Introduction
An estimated 0·5–1·2 million episodes of meningococcal disease occur every year, causing 50 000–135 000 deaths worldwide.1, 2 Neisseria meningitidis colonises the nasopharynx and is transmitted via large-droplet spread. Asymptomatic carriage is highest among adolescents, associated with social behaviours such as bedroom-sharing, smoking, kissing, and attending bars and clubs.3, 4, 5, 6 The most important disease-associated serogroups are A, B, C, W, and Y, with X being a recent concern in Africa.7 Results of post-implementation analyses of population-scale vaccination programmes show that meningococcal serogroup C conjugate (MCC) vaccines provide benefit not only by direct protection of vaccinated individuals, but also more importantly through the interruption of transmission—ie, herd protection,8, 9, 10 a factor that enhances public health effect and cost-effectiveness.11
In addition to quadrivalent glycoconjugate vaccines against serogroups A, C, W, and Y, such as MenACWY-CRM (Menveo, Novartis Vaccines, Siena, Italy), a multicomponent serogroup B meningococcal vaccine, 4CMenB (Bexsero, Novartis Vaccines) has been licensed in the European Union, Australia, and Canada. 4CMenB contains Neisseria heparin binding antigen (subvariant 1.2) fused with accessory protein 953, Neisserial adhesin A (subvariant 3.1), factor H binding protein (subvariant 1.1) fused with accessory protein 936, and the outer membrane vesicle (OMV) from N meningitidis strain NZ98/254 (OMV NZ) derived from the MeNZB vaccine.12, 13
Our study aimed to assess the effect of 4CMenB and MenACWY-CRM vaccination on meningococcal carriage rates in university students in England.
Section snippets
Study design and participants
This trial was a randomised, observer-blind, controlled phase 3 study undertaken at ten study centres in England.
Patients
Eligible participants were healthy men and women aged 18–24 years attending university, who were available for all scheduled visits with no history of serogroup B meningococcal vaccination, meningococcal disease or contact with it, significant infection of any nature within the previous 7 days, or use of antibiotics within 72 h of enrolment. We excluded pregnant women, nursing
Results
2968 individuals were enrolled (Sept 21 to Dec 21, 2010) and 2954 were randomly assigned (figure 1). 14 participants were not assigned to any of the groups because of protocol deviations; these individuals did not receive any study vaccinations. Table 1 shows the demographic variables and baseline N meningitidis carriage rates in the treatment groups. No serogroup A N meningitidis was detected in any individual. More than 99% of the randomly assigned individuals were included in the MITT
Discussion
During the 1 year of follow-up, the MenACWY-CRM and 4CMenB vaccines significantly reduced carriage of N meningitidis (panel). MenACWY-CRM affected carriage of vaccine serogroups whereas 4CMenB had a broad effect. The broad effect is not surprising, because, although 4CMenB is characterised as a MenB vaccine, antigens in the vaccine are also present in, and able to induce bactericidal antibodies against, non-serogroup B strains as well.15 However, neither vaccine showed any immediate effect on
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