Development of a Serum Bactericidal Antibody Assay for Neisseria meningitidis serogroup X

Katz, Sara Elizabeth (2021) Development of a Serum Bactericidal Antibody Assay for Neisseria meningitidis serogroup X. Masters by Research thesis (MSc), Manchester Metropolitan University.

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Abstract

Background: Invasive meningococcal disease (IMD) affects approximately 1.2 million people worldwide annually. Prevention of IMD is provided through conjugate vaccines; however, no licensed vaccine is currently available to protect against meningococcal serogroup X associated infection. This study aimed to provide seroprevalence data to assess natural immunity to serogroup X within the African sub-Saharan meningitis belt. Following this, a serum bactericidal antibody (SBA) assay, used to measure SBA to serogroup X, was developed and validated. This assay will be used in the phase 3 trial for a pentavalent conjugate vaccine containing serogroup X, NmCV-5 (Serum Institute India), prior to its introduction into the meningitis belt. Methods: The SBA assay was used to conduct a seroprevalence study, measuring SBA titres to serogroup X in 377 serum samples, acquired from Niger, West Africa, within the meningitis belt. The serogroup X SBA assay was then validated for selectivity/specificity, assay precision/reproducibility, linearity, and stability. Results: Seroprevalence data obtained found that natural immunity to Neisseria meningitidis serogroup X were present in 52.3% of study participants. The highest protective titres (≥8) to serogroup X were seen in age group 5-14 years-old (73.9%) and lowest in ages <1 year old (0%). There was also a correlation observed between participants who had received previous meningococcal vaccination (not containing serogroup X polysaccharide) and an increase in SBA titre to serogroup X. The serogroup X SBA assay was validated successfully for all parameters, except in Assay Precision/Reproducibility – Accuracy, and Linearity. These parameters require further post-study research if the SBA assay is to be used for the NmCV-5 phase 3 trial. Conclusion: Seroprevalence data supported the need for implementation of the NmCV-5 vaccine into the at-risk communities within the meningitis belt. Validation data obtained for the serogroup X SBA assay was encouraging, and work will continue post-study to validate to the required standard. Following successful validation, the serogroup X SBA assay can be used in clinical trials for future meningococcal conjugate vaccines, including NmCV-5.