Abstract

BackgroundMucosal antibodies against capsular polysaccharides offer protection against acquisition and carriage of encapsulated bacteria like Neisseria meningitidis serogroup C. Measurements of salivary antibodies as replacement for blood testing has important (cost-effective) advantages, particular in studies that assess the impact of large-scale vaccination or in populations in which blood sampling is difficult. This study aimed to estimate a threshold for meningococcal IgG salivary antibody levels to discriminate between unprotected and protected vaccinated individuals.MethodsMenA-, MenC-, MenW- and MenY-polysaccharide (PS) specific IgG levels in serum and saliva from participants in a meningococcal vaccination study were measured using the fluorescent-bead-based multiplex immunoassay. Functional antibody titers in serum against the four serogroups were measured with serum bactericidal assay using rabbit complement (rSBA). A threshold for salivary IgG was determined by analysis of ROC curves using a serum rSBA titer ≥128 as correlate of protection. The area under the curve (AUC) was calculated to quantify the accuracy of the salivary test and was considered adequate when ≥0.80. The optimal cut-off was considered adequate when salivary IgG cut-off levels provided specificity of ≥90%. True positive rate (sensitivity), positive predictive value, and negative predictive value were calculated to explore the possible use of salivary antibody levels as a surrogate of protection.ResultsThe best ROC curve (AUC of 0.95) was obtained for MenC, with an estimated minimum threshold of MenC-PS specific salivary IgG ≥3.54 ng/mL as surrogate of protection. An adequate AUC (> 0.80) was also observed for MenW and MenY with an estimated minimal threshold of 2.00 and 1.82 ng/mL, respectively. When applying these thresholds, all (100%) samples collected 1 month and 1 year after the (booster) meningococcal vaccination, that were defined as protective in the saliva test for MenC, MenW and MenY, corresponded with concomitant serum rSBA titer ≥128 for the respective meningococcal serogroups.ConclusionThe saliva test offers an alternative screening tool to monitor protective vaccine responses up to one year after meningococcal vaccination against MenC, MenW and MenY. Future (large) longitudinal vaccination studies evaluating also clinical protection against IMD or carriage acquisition are required to validate the currently proposed threshold in saliva.

Highlights

  • Mucosal antibodies against capsular polysaccharides offer protection against acquisition and carriage of encapsulated bacteria like Neisseria meningitidis serogroup C

  • Sample selection For assessment of meningococcal serogroup C (MenC) antibody levels, longitudinal serum and saliva samples for all three time points were available from 416 participants, whereas these were available for meningococcal serogroup A (MenA), meningococcal serogroup W (MenW) and Meningococcal serogroup Y (MenY) from 197, 200 and 199 participants, respectively

  • In this study, we showed that salivary IgG levels significantly correlated with bactericidal antibody titers in serum after both primary (MenA, MenW and MenY) and booster (MenC) vaccination

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Summary

Introduction

Mucosal antibodies against capsular polysaccharides offer protection against acquisition and carriage of encapsulated bacteria like Neisseria meningitidis serogroup C. Invasive meningococcal disease (IMD) remains a major public health concern due to the high mortality and morbidity. To prevent this invasive and potentially devastating infection, sufficient levels of functional antibodies in serum have been shown to be important [1]. Meningococcal polysaccharide (PS) conjugate vaccines (MCVs) are able to induce functional bactericidal serum antibodies that, upon binding to invading meningococci, activate complement leading to lysis of the bacteria and enhanced phagocytosis [3, 4]. A bactericidal titer of ≥8 is considered as correlate of protection baby rabbit complement [6, 7]. A more conservative threshold of ≥128 is often used in the SBA applying rabbit complement (rSBA) [1]

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