An Observational Follow up Study of a Phase II/III, Open Label, Randomised Study of the Safety, Reactogenicity and Immunogenicity of a Single Dose of Meningococcal ACWY Conjugate Vaccine (Menveo, Glaxosmithkline or Nimenrix, Pfizer) in Adolescents Who Were Primed With Meningitec, Menjugate or Neisvac-C During Preschool Vaccination

The UK was the first country in the world to introduce the meningococcal serogroup C conjugate vaccine (MCC) into its routine immunisation schedule in 1999. This very effectively reduced the incidence of disease, which was highest in those younger than 1 year through its routine use in the infant immunisation schedule, and those aged around 15-17 years through a catch up campaign . Subsequently, the meningococcal vaccination schedule has undergone several revisions, including:

• 2006 - a reduction in the number of doses given to infants from the manufacturer advised three to the JCVI instructed two with the combination of the MCC dose in the second year of life with the Hib vaccine, in the form of Menitorix
• 2013 - a further reduction to a single dose in infancy and the introduction of a booster in teenage years due to studies demonstrating that antibody persistence was short lived through childhood
• 2015 - the amendment of the teenage booster dose from MCC to a quadrivalent meningococcal conjugate vaccine to address the increasing incidence of serogroup W disease in this age group (PHE website - Meningococcal data), and the introduction of Bexsero into the infant schedule ostensibly to address meningococcal B disease but with the potential for cross protection against other serogroups, which is currently being assessed in another NVEC study.
• 2016 - removal of the MCC at 3 months of age.

Given the previous demonstration of poor antibody persistence of MenC antibodies two years following the 2006 schedule, with only 43%, 22% and 23% of children achieving SBA titres ≥8 two years following a booster dose of Menitorix™ when primed with NeisVac-C™, Menjugate™ and Meningitec™, respectively, there is concern about the protection afforded by the quadrivalent vaccine administered at around 14 years of age, and whether this will provide protection into young adulthood when the risk of disease is high.

In a previous study by this group (Eudract number 2010-022505-18) , adolescents aged 16-19 years were randomised to receive one of two licensed meningococcal ACWY conjugate vaccines:

1. Menveo™ (GSK) This vaccine contains bacterial capsular oligosaccharides for serogroups A, C, W, and Y conjugated to a protein carrier, CRM197, which is a nontoxigenic natural variant of diphtheria toxin. The MenACWY vaccine has been tested in several age groups and has been shown to be generally well tolerated and immunogenic. Menveo™ is indicated for use in those from 2 years of age and in those at risk.
2. Nimenrix (Pfizer) This vaccine contains bacterial capsular oligosaccharides for serogroups A, C, W, and Y conjugated to Tetanus Toxoid (TT). This MenACWY-TT vaccine has been tested in several age groups and has been shown to be safe and immunogenic. It is indicated for use from 12 months of age and in those at risk.