Determining immunological correlates of protection against group B streptococcus colonization in pregnant women

Kwatra, Gaurav
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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.
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