Abstract

AbstractNeisseria meningitidis is one of the leading causes of bacterial meningitis and septicemia in children. Vaccines containing the purified polysaccharide capsule from the organism, a T cell-independent antigen, have been available for decades but do not appear to provide protection in infancy or immunologic memory as measured by antibody responses. By contrast, T cell-dependent serogroup C protein-polysaccharide conjugate vaccines protect against serogroup C meningococcal disease from infancy onward and prime for immunologic memory. We compared the magnitude and kinetics of plasma cell and memory B-cell responses to a meningococcal plain polysaccharide vaccine and a serogroup C glycoconjugate vaccine in adolescents previously primed with the conjugate vaccine. Plasma cell kinetics were similar for both vaccines, though the magnitude of the response was greater for the glycoconjugate. In contrast to the glycoconjugate vaccine, the plain polysaccharide vaccine did not induce a persistent immunoglobulin G (IgG) memory B-cell response. This is the first study to directly show that serogroup C meningococcal glycoconjugate vaccines induce persistent production of memory B cells and that plain polysaccharide vaccines do not, supporting the use of the conjugate vaccine for sustained population protection. Detection of peripheral blood memory B-cell responses after vaccination may be a useful signature of successful induction of immunologic memory during novel vaccine evaluation.

Highlights

  • Neisseria meningitidis is one of the leading causes of bacterial meningitis and septicemia in children worldwide and a cause of more than 50 000 deaths per year.[1]

  • The capsular polysaccharide of serogroup C N meningitidis is the antigen used in meningococcal vaccines that protect against serogroup C strains

  • The relative contributions of antibody persistence and priming to long-term vaccine-induced protection have become a central issue in protein–polysaccharide conjugate vaccine immunobiology. This issue was highlighted by an analysis of serogroup C meningococcal (MenC) glycoconjugate surveillance data following the introduction of the routine use of MenC vaccine in the United Kingdom

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Summary

Introduction

Neisseria meningitidis is one of the leading causes of bacterial meningitis and septicemia in children worldwide and a cause of more than 50 000 deaths per year.[1]. The relative contributions of antibody persistence and priming to long-term vaccine-induced protection have become a central issue in protein–polysaccharide conjugate vaccine immunobiology This issue was highlighted by an analysis of serogroup C meningococcal (MenC) glycoconjugate surveillance data following the introduction of the routine use of MenC vaccine in the United Kingdom. Several authors (A.J.P., E.R.M.) have conducted clinical trials on behalf of Oxford University that were sponsored by a company (Chiron Vaccines) or a competitor (Wyeth, GlaxoSmithKline, Sanofi Pasteur, Sanofi Pasteur MSD) of a company whose potential product was studied in the present work. We hypothesized that comparing the antigen-specific B-cell response of a glycoconjugate MenC vaccine (MenCC) and a plain polysaccharide serogroup A/C meningococcal vaccine (MenCPS), by use of a B-cell ELISpot assay, would allow the differentiation of the B-cell characteristics related to immediate antibody production from those specific to immunologic priming

Subjects and vaccines
Preparation of PBMCs
Preparation of ELISpot plates
Detection of plasma cells
Detection of memory B cells
Statistical analysis
Results
MenC IgG antibody response to vaccination
Plasma cells
Correlation with antibody responses
Memory B cells
Discussion
Plasma cell responses
Full Text
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