Vaccine prevention of capsular group C meningococcal disease in childhood

Abstract

Invasive capsular group C meningococcal (MenC) disease remains a prevalent cause of death and disability in children that may be prevented by vaccination. The introduction of MenC conjugate (MenCC) vaccines in immunisation programmes has increased the burden of vaccine injections administered in childhood. Consequently, the possibility of decreasing the number of Men CC vaccine injections needs to be investigated, as has been studied in this thesis. The immunogenicity of a novel combined Haemophilus irifhtenzae type b (Hib )-MenC conjugate vaccine (HibMenC-TT), investigated in a Phase 3 trial, was found to be non-inferior to a licensed MenC-CRM197 vaccine following a prime and boost schedule, after which 94.8% of participants had MenC serum bactericidal antibody titres, using rabbit complement, (rSBA) 2:1: 128 irrespective of the vaccine formulation used for priming. Subsequently, an investigation of the immunogenicity of reduced MenCC prime and boost schedules in a Phase 4 trial, demonstrated that, after a 12 month Hib-MenC-TT boost, a single infant MenC-CRM197 vaccine priming schedule was non-inferior to two infant dose MenC-CRM197 priming (MenC rSBA geometric mean titres 660 vs 295, difference in mean log10 MenC rSBA of 0.35). After Hib-MenC-TT boosting, only a single infant dose MenC-TT priming schedule was found to induce robust MenC rSBA titres that persisted up till 24 months of age. Data from these trials supported the introduction of the Hih-MenC-TT booster dose and the subsequent reduction of the number of MenCC infant priming doses in the UK immunisation schedule. Furthermore, these results could be used to guide the implementation of a MenCC immunisation programme in Malta, where an epidemiological study performed as part of this thesis demonstrated that the overall, and specifically the infant, incidence rates of MenC disease are much higher than those in Europe. I