Abstract
BackgroundNeisseria meningitidis is a globally important cause of meningitis and septicaemia. Twelve capsular groups of meningococci are known, and quadrivalent vaccines against four of these (A, C, W and Y) are available as plain-polysaccharide and protein-polysaccharide conjugate vaccines. Here we apply contemporary methods to describe B-cell responses to meningococcal polysaccharide and conjugate vaccines.MethodsTwenty adults were randomly assigned to receive either a meningococcal plain-polysaccharide or conjugate vaccine; one month later all received the conjugate vaccine. Blood samples were taken pre-vaccination and 7, 21 and 28 days after vaccination; B-cell responses were assessed by ELISpot, serum bactericidal assay, flow cytometry and gene expression microarray.ResultsSeven days after an initial dose of either vaccine, a gene expression signature characteristic of plasmablasts was detectable. The frequency of newly generated plasma cells (CXCR3+HLA-DR+) and the expression of transcripts derived from IGKC and IGHG2 correlated with immunogenicity. Notably, using an independent dataset, the expression of glucosamine (N-acetyl)-6-sulfatase was found to reproducibly correlate with the magnitude of immune response. Transcriptomic and flow cytometric data revealed depletion of switched memory B cells following plain-polysaccharide vaccine.ConclusionsThese data describe distinct gene signatures associated with the production of high-avidity antibody and a plain-polysaccharide-specific signature, possibly linked to polysaccharide-induced hyporesponsiveness.
Highlights
Neisseria meningitidis is a globally important cause of meningitis and septicaemia
The rise in bactericidal antibody following an initial dose of either plain polysaccharide or conjugate Group A (MenACWY) vaccine is similar and is not boosted by a subsequent dose of conjugate vaccine We evaluated B-cell responses in 20 healthy adults vaccinated with either MenACWY-Cross-reactive material (CRM) or MenACWY-PS, followed by an additional dose of MenACWY-CRM 28 days later
No statistically significant differences were seen in measured antimeningococcal capsular group A (MenA) or Group C meningococcus (MenC) serum bactericidal assay (SBA) Geometric mean titre (GMT) between the four vaccine groups after the first or second dose of vaccine (Fig. 1a)
Summary
Twelve capsular groups of meningococci are known, and quadrivalent vaccines against four of these (A, C, W and Y) are available as plain-polysaccharide and protein-polysaccharide conjugate vaccines. We apply contemporary methods to describe B-cell responses to meningococcal polysaccharide and conjugate vaccines. Meningococcal polysaccharide vaccines provide only short-term protection in adults, have limited immunogenicity in early childhood and have been associated with hyporesponsiveness following subsequent doses [6, 7]. These shortcomings have been attributed to the T cell-independent nature of responses to polysaccharides that do not drive the formation of immunological memory.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
