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Porin A-specific antibody avidity in patients who are convalescing from meningococcal B disease
Clementien L Vermont1, Harry H van Dijken, Ronald de Groot
1Laboratory for Vaccine Research, Netherlands Vaccine Institute, 3720 AL Bilthoven, The Netherlands.
Insights
Children convalescing from meningococcal disease showed PorA-specific antibody avidity. Antibody avidity was highest against the infecting PorA subtype, but lower than after vaccination.
Area of Science:
- Immunology
- Microbiology
- Vaccinology
Background:
- Porin A (PorA) is the primary antigen in vaccines against serogroup B meningococci.
- PorA determines the serosubtype of Neisseria meningitidis and elicits antibody responses.
- Previous studies indicate PorA-based vaccines induce high-avidity antibodies in children.
Purpose of the Study:
- To characterize the immune response in children post-meningococcal infection.
- To assess antibody avidity and specificity following infection with a specific PorA subtype (P1.7-2,4).
- To compare antibody avidity after natural infection versus vaccination.
Main Methods:
- Collected acute- and convalescent-phase sera from 21 children with meningococcal septic shock.
- Measured serum bactericidal antibody titers, IgG isotype distribution, and antibody avidity.
- Assessed avidity against homologous, heterologous PorA subtypes, and PorA-negative strains.
Main Results:
- Convalescent sera showed minimal bactericidal activity against the infecting strain.
- IgG response was dominated by IgG(1) and IgG(3) isotypes.
- Geometric Mean Avidity Index (GMAI) was significantly higher for the homologous PorA subtype (P1.7-2,4) compared to heterologous or PorA-negative strains (57% vs. 35% and 23%).
- Antibody avidity after invasive meningococcal disease was lower than observed after vaccination in toddlers.
Conclusions:
- The immune response to Neisseria meningitidis infection is PorA subtype-specific.
- Antibody avidity following invasive meningococcal disease is lower than that induced by vaccination.
- Findings highlight the importance of PorA in vaccine-induced immunity and suggest potential for improved vaccine strategies.
Abstract:
Porin A (PorA), which determines the serosubtype of Neisseria meningitidis, is the main antigen of a candidate vaccine against serogroup B meningococci, which has been shown to induce high-avidity antibodies in children. We characterized the immune response of children after convalescing from meningococcal infection with a serosubtype P1.7-2,4 strain. Acute- and convalescent-phase sera of 21 children with meningococcal septic shock caused by strains with PorA subtype P1.7-2,4 were collected. The serum bactericidal antibody titers, IgG isotype distribution, and antibody avidity were measured. We determined whether the differences in avidity of anti-outer membrane vesicle antibodies were PorA specific. Serum bactericidal activity against H44/76 P1.7-2,4 was <4 in all convalescent sera. The IgG isotype distribution of the convalescent sera was dominated by IgG(1), followed by IgG(3), whereas no IgG(2) or IgG(4) was found. The geometric mean avidity index (GMAI) of convalescent sera measured against a strain with the identical subtype as the infective isolate was significantly higher than that against a strain with a heterologous PorA subtype or a PorA-negative mutant strain (57 versus 35 and 23%, respectively; p = 0.005 and p < 0.001). Geometric mean avidity titers were highest for P1.7-2,4, corresponding with the highest GMAI. The GMAI after invasive meningococcal disease was lower than after vaccination of healthy toddlers with a monovalent P1.7-2,4 outer membrane vesicle vaccine.
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