PROJECT SUMMARY/ABSTRACT Meningitis epidemics, primarily caused by N. meningitidis serogroup A, occur annually during the dry season in the African meningitis belt, leading to significant morbidity and mortality among the 450 million people living in this region. The introduction of MenAfriVac, a newly developed conjugate meningococcal serogroup A vaccine, in Burkina Faso, Mali, and Niger in December 2010 was the first ever population-based, preventive mass-vaccination campaign against meningococcal meningitis in the meningitis belt and the first- ever nationwide use of this vaccine. While clinical trials have demonstrated that MenAfriVac induces a stronger immune response than polysaccharide meningococcal serogroup A vaccines, the duration of protection provided by MenAfriVac is currently unknown. The persistence of the serogroup A-specific serum bactericidal antibody (SBA) response and the IgG response, both accepted correlates of protection against invasive disease, are key determinants of whether the MenAfriVac mass-vaccination campaign will successfully prevent the deadly epidemics of meningitis that have occurred in the region for the past century. Our goal is to address a critical barrier to progress in the field by evaluating the impact of the MenAfriVac mass-vaccination campaign. Specifically, we will assess the duration of protection provided by the vaccine up to five years after the population-based, mass-vaccination campaign targeted to all individuals aged 1-29 years in Bamako, Mali. We will determine when, if at all, population-level immunity begins to wane up to five years after mass- vaccination. Additionally, we will determine the most effective vaccination strategy, which can then be implemented both in Mali and other countries of the African meningitis belt in the future. We will evaluate the antibody persistence following the MenAfriVac mass-vaccination campaign by collecting prospective immunogenicity data from a random sample of 800 residents of Bamako, Mali, aged 1- 29 years at 18 months, 36 months, and 54 months after mass vaccination. Specifically, we aim to: 1.) determine the proportion of individuals with protective levels of serogroup A-specific SBA and IgG both overall and by age at each of the three post-vaccination time points, 2.) evaluate the significance of temporal changes in serogroup A-specific SBA and IgG titers both overall and by age up to five years post-vaccination, and 3.) assess potential risk factors, such as age at vaccination, prior polysaccharide meningococcal vaccination, nutritional status, and socioeconomic status, for low SBA and IgG titers at each of the three post-vaccination time points. Statistical methods will be used to provide evidence for the degree of vaccine-induced antibody persistence and to evaluate risk factors for low antibody response. The results will be used to develop and implement the most effective vaccination strategy in the countries of the African meningitis belt, to determine if there is a need for additional booster doses of vaccine in any age group after five years, and to increase our understanding of the mechanism by which MenAfriVac provides protection against invasive disease.

PROJECT NARRATIVE Seasonal meningitis outbreaks caused primarily by Neisseria meningitidis serogroup A are responsible for significant morbidity and mortality among the nearly 450 million people living in the African meningitis belt. In December 2010, the first-ever preventive meningitis mass-vaccination campaign using a newly developed conjugate meningococcal serogroup A vaccine was launched in this region. We aim to evaluate the persistence of the protective antibody response generated by this vaccine in Bamako, Mali, for up to five years post-vaccination. Our goal is to determine the most effective vaccination strategy capable of maintaining protective levels of immunity in the population and ending the devastating epidemics of meningitis.