Determining immunological correlates of protection against group B streptococcus colonization in pregnant women
Date
2016
Authors
Kwatra, Gaurav
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Abstract
Introduction: Maternal recto-vaginal colonization with Group B Streptococcus (GBS) is
the major risk factor for invasive GBS disease in newborn’s. Maternal vaccination against
GBS during pregnancy may prevent or reduce subsequent recto-vaginal colonization in
women, which could lower fetal/newborn exposure to GBS and contribute to reducing
GBS associated infections during early infancy. In this study we determined the
immunological correlates of protection against GBS colonization in black African pregnant
women.
Methods: We compared GBS serotype-specific serum IgG, mucosal IgG, mucosal IgA
and cellular immune responses in relation to GBS rectovaginal acquisition and clearance in
pregnant women from 20 to 37+ weeks of gestational age. Furthermore, we also evaluated
different media for isolation of GBS from vaginal and rectal swabs.
Results: The prevalence of recto-vaginal GBS colonization was 33.0%, 32.7%, 28.7% and
28.4% at 20-25 weeks, 26-30 weeks, 31-35 weeks and 37+ weeks of gestational age,
respectively. The most common identified serotypes were Ia (39.2%), III (32.8%) and V
(12.4%). The cumulative overall recto-vaginal acquisition rate of new serotypes during the
study was 27.9%, including 11.2%, 8.2% and 4.3% for serotypes Ia, III and V,
respectively. The recovery of GBS from rectal swabs was significantly higher from direct
plating on chromogenic medium (p<0.0001) than from selective broth method.
New-acquisition of GBS was inversely correlated with serotype-specific serum IgG
concentration for serotype III (p=0.009) and OPA titer for serotype Ia and III (p<0.001 for
both) at time of enrolment. Serum IgG concentration significantly associated with
protection against recto-vaginal acquisition of the homotypic serotype was ≥1 μg/ml for
serotype V (p=0.039), ≥3 μg/ml for serotype Ia (p=0.043) and III (p=0.023). Mucosal IgG
correlated significantly with serum IgG with Rho values of 0.839, 0.621 and 0.426 (all
p<0.001) for serotype Ia, III and V, respectively. The clearance of serotype-specific GBS
recto-vaginal colonization during pregnancy was positively associated with presence of
homotypic capsular ELISpot IFN-γ positivity for serotype III (p=0.008)
Conclusion: Maternal GBS colonization could be used as end point to evaluate efficacy of
GBS vaccine. A serotype-specific capsular polysaccharide based GBS vaccine able to elicit
both humoral and cell-mediated capsular immune responses could confer protection
against EOD by reducing the exposure of the newborn’s to GBS colonization during the
peri-partum period.
Description
A thesis submitted to the Faculty of Health Sciences, University of the
Witwatersrand, Johannesburg, in fulfilment of the requirements for the degree of
Doctor of Philosophy
Johannesburg, 2016