Assessment of Avidity of Igg Antibodies Against Meningococcal Serogroup A Polysaccharide and Its Correlation with Pre-Existing Data on Bactericidal Activity in Meningitis Patients and Controls From Ethiopia
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Date
2010-12
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Addis Ababa University
Abstract
Studies in the “meningitis belt” countries such as Burkina Faso, Gambia, Ethiopia and Sudan
showed the presence of high antibody levels against serogroup A capsular polysaccharide (APS)
of Neisseria meningitidis. The antibody concentrations usually exceeded the suggested protective
antibody level (≥ 2μg/ml of total Ig against APS). In spite of this, the populations in this area are
affected by recurring epidemics of meningococcal meningitis. Therefore, to determine the level of
anti-APS IgG that correlates with protection in the “meningitis belt” area, it may be appropriate to
consider the quality of the antibodies along with quantity. Though quality of antibodies might be
affected by several factors, this study considered the avidity of antibodies against APS, which is
believed to better correlate with serum bactericidal activity (SBA). Two modified ELISA
methods using the chaotropic agent ammonium thiocyanate (NH4SCN) that disrupts weak
antibody binding were employed to measure avidity indices (AI) of anti-APS IgG. In one of the
methods a constant concentration of SCN- and varying serum dilutions, and in the other, a single
serum dilution with varying SCN- concentrations were used. 114 acute and convalescent sera
from Ethiopian meningitis patients and controls were analysed. High correlation was observed
between the avidity indices calculated from the two methods (r=0.8). When assaying patient sera,
anti-APS IgG concentrations correlated with SBA using baby rabbit sera as a complement source
(rSBA) both before and after elution with 120mM SCN- (r=0.64 and r=0.65, p<0.0001). Similar
results were observed with SBA by employing human sera as a complement source (hSBA) (r =
0.46 and 0.41 p<0.0001). However, correlation between AI and SBA was only seen in the late
convalescent sera. The anti-APS IgG rose in early convalescent but declined in late convalescent
sera though the AI remained high in the late convalescent sera indicating affinity maturation. Age
dependent increase in IgG concentration was seen in controls and late convalescent sera, and
lower levels of avidity indices were seen in sera of the test groups aged 0.5-6 years. Further
studies to standardize avidity measurement and other factors that might affect the quality of
antibody responses (e.g. IgG subclasses) will be necessary to obtain a correct picture of protective
immunity against serogroup A N. meningitidis infections in the “meningitis belt” of Africa.
Key words – Avidity index, Capsular polysaccharide A, ELISA, “Meningitis belt”, Serum
bactericidal activity, Neisseria meningitidis A
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Keywords
Avidity index, Capsular polysaccharide, A, ELISA, Meningitis belt, Serum bactericidal activity, Neisseria meningitidis A