Marshall, HelenSullivan, ThomasAndrews, RossMcMillan, Mark2021-10-182021-10-182021https://hdl.handle.net/2440/132672South Australia (SA) has one of the highest notification rates of invasive meningococcal disease (IMD) and, unlike other jurisdictions, serogroup B meningococci has been the predominant cause over the last two decades. Asymptomatic pharyngeal carriage is substantially higher in adolescents and young adults than other age groups. Adolescents and young adults are the critical population in the transmission of meningococcal bacterium and the primary target group for herd protection strategies. In 2013, 4CMenB vaccine was licensed for use by the Therapeutic Goods Administration in Australia against serogroup B disease. However, 4CMenB is not included as part of the National Immunisation Program for all children, or adolescents. This decision was in part based on the lack of information about the extent and duration of a herd protection effect from meningococcal B vaccines. As meningococcal B vaccines have been developed with novel technologies, herd protection effects seen with conjugate meningococcal vaccines cannot be guaranteed, and the evidence for their effectiveness against IMD is limited. This is the first-ever study assessing meningococcal carriage in Australian adolescents. The overarching aim of this thesis was to establish if the 4CMenB vaccine is effective in reducing meningococcal carriage. Secondary aims were to establish the vaccine impact against disease in adolescents, as well as carriage prevalence, and risk factors for carriage. The principal findings were: 1. Carriage prevalence of N. meningitidis increased in each school year, from 2.2 % in year 10, 3.3% in year 11, and 5.5% in year 12 students, to 9.1% in school leavers (mean age 18.5 years). 2. In the largest randomised interventional meningococcal carriage study to date: a. 4CMenB had no impact on carriage of disease-causing meningococci in adolescents 12 months after vaccination. b. 4CMenB had no effect on carriage density in those with meningococcal carriage at 12 months. c. Higher meningococcal carriage density was associated with a greater risk of carriage 12 months later. 3. Following the state-wide RCT, there were approximately 15 (95% confidence interval (CI), 3 to 19) less serogroup B IMD cases in the post-vaccination period (June 2017-2019) than the number of predicted cases. 4. Year of schooling (age), having a current respiratory infection, smoking cigarettes or water-pipe, attending pubs/clubs, kissing intimately, drinking alcohol, and not being of Asian ethnicity were all associated with an increased risk of meningococcal carriage. 5. The state-wide RCT led to a 35% absolute increase in 4CMenB vaccine coverage in school leavers from 2018 to 2019, but this did not correspond with a reduction in meningococcal carriage between 2018 and 2019. 6. Meta-analysis showed that meningococcal conjugate C, ACWY, as well as outer membrane vesicle vaccines are effective at reducing IMD. Meningococcal B vaccines did not reduce group B meningococcal carriage. In conclusion, 4CMenB immunisation programs should focus on direct (individual) protection for groups at greatest risk of meningococcal disease, rather than the potential for herd protection. The 4CMenB vaccine demonstrated that it provides significant reduction in group B IMD in adolescents following immunisation of high school students, supporting its use in adolescents.en4CMenBmeningococcalcarriageNeisseria Meningitidisherd protectionThesis