Vaccine prevention of meningococcal disease in adolescents and travellers

Invasive meningococcal disease (IMD) is endemic worldwide. Adolescence and travel to regions with hyper-endemic or epidemic disease are associated with a higher risk of IMD. Unpredictable variation in the serogroup distribution of Neisseria meningitidis over time and between different geographical areas is characteristic of the epidemiology of IMD. Currently serogroups B and C are most prevalent in Europe and in the US, where serogroup Y has also become a major cause of IMD over the last 20 years. In Asia, serogroups A and C predominate whilst serogroups A and W-135, and more recently X, have caused outbreaks in countries in the meningitis belt of sub-Saharan Africa. Despite appropriate and timely management, meningococcal meningitis and septicaemia are associated with an overall mortality of 8–14% and with permanent disabilities, such as amputations, hearing loss and neuro-developmental impairment in 10–19% of survivors.1 Vaccination remains the most effective strategy for preventing IMD in at risk individuals. A quadrivalent meningococcal serogroup A, C, W-135 and Y (MenA, MenC, MenW-135 and MenY) glycoconjugate vaccine, which utilises CRM197 as the carrier protein (MenACWY-CRM, Menveo, Novartis Vaccines and Diagnostics, Siena, Italy) was licensed by the European Medicines Agency in March 2010. MenACWY-CRM is currently the only quadrivalent meningococcal glycoconjugate vaccine available in Europe that provides broad protection against IMD in at risk individuals aged 11–65 years. MenACWY-CRM was licensed in February 2010 by the Food and Drug Administration for immunisation of 11–55 year-olds in the US where a diphtheria toxoid quadrivalent meningococcal conjugate vaccine, MenACWY-DT (Menactra, Sanofi Pasteur, Swiftwater, PA, USA), is also available for use in 2–55 year-old individuals. The threat of IMD has been well recognised during travel to destinations hosting large numbers of people originating from different international locations, as occurs during the Hajj and Umrah pilgrimages in Saudi Arabia. N. meningitidis is a sole human pathogen which is found as a coloniser of the nasopharynx in 10% of the adult population during non-epidemic settings.2 Nasopharyngeal carriage provides a continuous reservoir for human to human transmission which occurs through mucosal exposure to infected aerosol droplets and secretions from close contact with asymptomatic carriers or with individuals with invasive disease. The inevitable overcrowding associated with mass gatherings has been associated with increased acquisition of meningococcal carriage. Progression to IMD is known to occur within 1–14 days of exposure to N. meningitidis.1 Although a rare event, IMD has occurred at a higher frequency in pilgrims and in their household contacts on their return to their home country, leading to international outbreaks.3 An outbreak caused by serogroup A ST5 clonal complex occurred during the 1987 Hajj season following which immunisation with a MenA polysaccharide vaccine became mandatory to get a Hajj visa from 1988.4 The 1992 and 1997 Umrah seasons were also marked by MenA outbreaks which were controlled by immunisation with a MenAC polysaccharide vaccine.4 Subsequently, an unexpected outbreak by MenW-135 ST11 complex occurred during the Hajj season in 2000 which spread internationally with returning pilgrims.3 No further outbreaks have been documented since 2002 when immunisation with a quadrivalent polysaccharide MenACWY vaccine became a visa requirement for the Hajj. In the absence of a comprehensive MenB vaccine, broad protection against serogroups A, C, W-135 and Y (the most common serogroups worldwide besides MenB) by vaccination remains the most effective strategy for preventing IMD in at risk travellers. Changes in social behaviour during adolescence are thought to be the main contributors to the increased risk of IMD in this age group. Intimate kissing, visiting pubs, bars and discotheques, smoking, attendance to high schools and universities, and sleeping in college dormitories are associated with higher rates of meningococcal carriage which may reach 25% in 15–19 year-olds.2 Although the incidence of IMD is much less than in the first four years of life, adolescents bear the highest case fatality rate which reaches 22.5%.5 In the US 75% of meningococcal disease in ≥11 year-olds is caused by serogroups C, W-135 and Y whilst in Europe serogroups B and C are responsible for most cases in 15–19 year-olds.6 The Advisory Committee on Immunization Practices (ACIP) in the US recommends routine vaccination of 11–18 year-olds with one of the licensed quadrivalent MenACWY glycoconjugates. A routine MenC or, depending on the meningococcal serogroup epidemiology, a MenACWY conjugate vaccine booster dose for 12 year-old adolescents who had received the routine MenC conjugate vaccine in infancy or in the second year of life, has also been recommended in Canada since 2009. In view of the different serogroup epidemiology no recommendations for routine MenACWY adolescent vaccination have yet been made in European countries. Although meningococcal pure polysaccharide vaccines have been used successfully in outbreaks and to protect travellers, their T-cell independent nature results in an age-dependent variation in post-immunisation meningococcal bactericidal antibodies, with poor immunogenicity in children <2 years old, an inability to cause a sustained reduction in meningococcal carriage, and rapid waning of functional antibodies necessitating boosting every 3–5 years. However, repeated doses result in hyporesponsiveness which may theoretically increase the susceptibility to IMD.7 By contrast, the design of a T-cell dependent antigen through conjugation of MenACWY poly/oligosaccharides to a carrier protein, such as CRM197, results in robust meningococcal bactericidal antibodies from infancy, boosting of bactericidal antibody with repeated doses and a reduction in meningococcal carriage rates, thus limiting transmission and contributing to herd immunity. A single intramuscular dose of MenACWY-CRM in 11–65 year-olds induces robust immunity against all four vaccine serogroups with 75–96% of 11–18 year-old adolescents; 69–94% of 19–55 year-olds and 87–94% of 56–65 year-olds having a meningococcal serum bactericidal antibody titre, using human complement, (hSBA) of ≥1:8 against all serogroups one month after vaccination.8 Seroprotection, as measured by SBA of ≥1:8 (using rabbit complement), against all serogroups lasts for at least 21 months in 72–97% of adolescents.9 One month after vaccination the immunogenicity of MenACWY-CRM is non-inferior for all serogroups to a pure polysaccharide MenACWY vaccine comparator in 11–17 and 56–65 year-olds, and to MenACWY-DT in 11–55 year-olds.8 Tenderness, redness and induration at the vaccination site, headache, nausea and malaise are common reactions that occur at a frequency of ≥1/10 in 11–65 year-old vaccinees following immunisation with MenACWY-CRM.8 In view of their much greater benefits, MenACWY glycoconjugates are expected to be recommended in preference to pure polysaccharide MenACWY vaccines to adolescents and Hajj or Umrah pilgrims, at least in countries where both preparations are licensed. Following the recent licensure of MenACWY-CRM, broad and robust protection against serogroup A, C, W-135 and Y disease can now also be provided in European countries. DP has undertaken all the duties of authorship and is guarantor of the paper. None. None declared Not required.

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