Prevention of rare diseases: how revolutionary techniques can help vulnerable individuals-the example of serogroup B meningococcal infection.

In countries with established programmes for vaccination of infants, toddlers and adolescents with meningococcal conjugate vaccines, serogroup B invasive meningococcal disease remains the major cause of septicaemia and meningitis in the paediatric and adolescent age groups. Novartis has developed a serogroup B meningococcal vaccine, 4CMenB, to meet this need. We reviewed all 4CMenB studies. The studies found 4CMenB to be highly immunogenic when administered in all schedules, with protective antibody levels (serum bactericidal antibody titres ≥4 or ≥5 with human complement, hSBA) against serogroup B strains expressing vaccine antigens in >95% of vaccinated cohorts. When antibody levels waned, all tested groups demonstrated booster responses. Although possibly an underestimation, the Meningococcal Antigen Typing System (MATS) technique predicts that global coverage of 4CMenB against all serogroup B strains is in the range 66% (Canada) to 91% (USA). The vaccine was found to be generally well tolerated, although local and systemic reactions, notably fever in infants, typical of many vaccines, were increased following concomitant administration of 4CMenB with routine vaccines. When tested, prophylactic paracetamol significantly decreased the frequency and severity of reactions in infants, with no clinically significant impact on immunogenicity of 4CMenB or concomitant routine vaccines. The vaccine is approved for use in the following age groups in the European Union (2 months+), Canada (2 months through 17 years), Australia (2 months+) and Chile (2 months+), following clinical evaluation in 4843 infants and toddlers, and 1712 adolescents and adults, in schedules including a three-dose (2, 3, 4 or 2, 4, 6 months) and a two-dose (6-11 months) infant series with a booster in the second year of life, a two-dose series in toddlers (12-23 months) and children (2-10 years) given 2 months apart (with a booster at least in the EU), and a two-dose series in adolescents (11-17 years) given 1-6 months apart. 4CMenB presents a solution to the unmet medical need of offering protection against serogroup B invasive meningococcal disease in all age groups above 2 months.