The genomic epidemiology of <i>Neisseria meningitidis</i> carriage from a randomised controlled trial of 4CMenB vaccination in an asymptomatic adolescent population.

Abstract

Oropharyngeal carriage of <i>Neisseria meningitidis</i> is frequent during adolescence, representing a major source of invasive meningococcal disease. This study examined the impact of a serogroup B vaccination (<i>Bexsero</i>, GSK 4CMenB) programme on adolescent <i>N. meningitidis</i> carriage using genomic data. A total 34,489 oropharyngeal samples were collected as part of a state-wide cluster randomised-controlled trial in South Australia during 2017 and 2018 (NCT03089086). Samples were screened for the presence of <i>N. meningitidis</i> DNA by <i>porA</i> PCR prior to culture. Whole genome sequencing was performed on all 1772 <i>N. meningitidis</i> culture isolates and their genomes were analysed. Unencapsulated meningococci were predominant at baseline (36.3% of isolates), followed by MenB (31.0%), and MenY (20.5%). Most MenB were ST-6058 from hyperinvasive cc41/44, or ST-32 and ST-2870 from cc32. For MenY, ST-23 and ST-1655 from cc23 were prevalent. Meningococcal carriage was mostly unchanged due to the vaccination programme; however, a significant reduction in ST-53 capsule-null meningococci prevalence was observed in 2018 compared to 2017 (OR = 0.52; 95% CI: 0.30-0.87, p = 0.0106). This effect was larger in the vaccinated compared to the control group (OR = 0.37; 95% CI: 0.12-0.98, p = 0.0368). While deployment of the 4CMenB vaccination did not alter the carriage of hyperinvasive MenB in the vaccinated population, it altered the carriage of other <i>N. meningitidis</i> sequence types following the vaccination program. Our findings suggest 4CMenB vaccination is unlikely to reduce transmission of hyperinvasive <i>N. meningitidis</i> strains and therefore ongoing targeted vaccination is likely a more effective public health intervention. This work was funded by GlaxoSmithKline Biologicals SA.