Persistence of antibodies in laboratory staff immunized with quadrivalent meningococcal polysaccharide vaccine

Johannes Elias,Matthias Frosch,Ray Borrow,Angelika Tremmel,Ulrich Vogel,Jamie Findlow

doi:10.1186/1745-6673-8-4

Abstract

BackgroundOccupational exposure to live meningococci can potentially cause invasive meningococcal disease in laboratory staff. While, until recently, immunization with quadrivalent polysaccharide vaccine represented one cornerstone of protection, data on long-term persistence of antibodies in adults remain scarce.MethodsWe analyzed the relationship of antibody levels and time following quadrivalent polysaccharide vaccination (Mencevax® ACWY, GlaxoSmithKline) in a cross-sectional sample of 20 laboratory workers vaccinated at ages between 16.4 to 40.7 years from Germany. Sera were obtained 0.4 to 158.5 (median 35.3) months after vaccination. At the time of sampling, laboratory workers had been regularly exposed to meningococci for periods between 3.2 to 163.8 (median 41.2) months. Serum bactericidal assay (SBA) with rabbit complement and a microsphere-based flow analysis method were used to determine bactericidal titers and concentrations of IgG, respectively, against serogroups A, C, W135, and Y. Decay of antibodies was modeled using linear regression. Protective levels were defined as SBA titers ≥ 8.ResultsHalf-lives of SBA titers against serogroups A, C, W135, and Y were estimated at 27.4, 21.9, 18.8, and 28.0 months, respectively. Average durations of protection were estimated at 183.9, 182.0, 114.6, and 216.4 months, respectively. Inter-individual variation was high; using lower margins of 95% prediction intervals, minimal durations of protection against serogroups A, C, W135 and Y were estimated at 33.5, 24.6, 0.0, and 55.1 months, respectively. The proportion of staff with protective SBA titers against W135 (65.0%) was significantly lower than proportions protected against A (95.0%), C (94.7%), and Y (95.0%). Consistently, geometric mean titer (97.0) and geometric mean concentration of IgG (2.1 μg/ml) was lowest against serogroup W135. SBA titers in a subset of individuals with incomplete protection rose to ≥ 128 (≥ 8 fold) after reimmunization with a quadrivalent glycoconjugate vaccine.ConclusionsThe average duration of protection following immunization with a quadrivalent polysaccharide vaccine in adults was ≥ 115 months regardless of serogroup. A substantial proportion (approximately 23% according to our decay model) of adult vaccinees may not retain protection against serogroup W135 for five years, the time suggested for reimmunization.

Highlights

Occupational exposure to live meningococci can potentially cause invasive meningococcal disease in laboratory staff
Serum bactericidal assay (SBA) titers and Immunoglobulin class G (IgG) concentration against serogroup C was excluded for one individual, who was vaccinated with NeisVac-CW (Baxter Deutschland GmbH, Unterschleißheim, Germany), a glycoconjugate vaccine against serogroup C, six months after receiving polysaccharide vaccination
The proportion of individuals within our sample presumably protected against disease, as inferred by the rate of sera with titers ≥ 8, differed significantly across serogroups (Cochran’s Q: 13.2 on 3 degrees of freedom, p = 0.004); protection against serogroup W135 was lowest with 65.0%, while protection exceeded 94.7% for all other serogroups (Table 1)

Summary

Introduction

Occupational exposure to live meningococci can potentially cause invasive meningococcal disease in laboratory staff. Commonly known as the meningococcus, is a Gram-negative bacterium that colonizes the pharyngeal mucosa of approximately 10% of humans in an age-dependent manner [1]. In rare cases, it causes potentially deadly invasive disease in the form of meningitis or sepsis in previously healthy individuals. Most cases appear in infants and adolescents [2], but adults over the age of 25 are affected. According to their polysaccharide capsule, meningococci can be distinguished into twelve serogroups [3]. To date, licensed vaccines consisting of polysaccharide or glycoconjugate-formulations exist for the prevention of disease by serogroups A, C, W135, and Y

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