Elsevier

Vaccine

Volume 33, Issue 48, 27 November 2015, Pages 6793-6799
Vaccine

Correlates of protection of serotype-specific capsular antibody and invasive Group B Streptococcus disease in South African infants

https://doi.org/10.1016/j.vaccine.2015.10.019Get rights and content

Abstract

Background

Vaccinating pregnant women may prevent invasive Group B Streptococcus (GBS) disease in their young infants. In a low-middle income setting, we sought to determine an association between natural maternal antibody responses and the development of invasive GBS disease.

Methods

We undertook a matched case-control study in Johannesburg, South Africa. Maternal and infant antibody concentrations were compared between serotype-specific Ia and III GBS cases and well-baby controls in which the mother was colonized with the same serotype.

Results

The median maternal serotype Ia and III antibody concentrations (in μg/mL) were 0.05 (IQR: 0.02–0.24; n = 27) and 0.14 (IQR: 0.08–0.33; n = 29) in cases, and 0.29 (IQR: 0.06–1.60; n = 43) and 0.29 (IQR: 0.13–0.58; n = 31) in homotypic controls, respectively. A smaller proportion of cases as compared to homotypic controls had higher serotype Ia and III maternal antibody concentrations. Using Bayesian modeling, we demonstrated that the risk of invasive GBS disease was less than 10% with maternal antibody concentrations ≥6 μg/mL and ≥3 μg/mL for serotypes Ia and III, respectively.

Conclusions

Maternal capsular antibody concentrations are associated with the risk of invasive GBS disease in infants. In a low-middle income setting with a high burden of invasive disease, we have demonstrated a sero-correlate of protection for GBS serotypes Ia and III which could facilitate vaccine licensure.

Introduction

The burden of invasive Group B Streptococcus (GBS) disease in young infants is highest in low-middle income countries where current screening programs and intra-partum antibiotic prophylaxis (IAP) have been unsuccessful [1], [2]. Vaccinating women during pregnancy, which increases the transplacental transfer of protective antibodies, prevents illness in their young infants (as demonstrated for tetanus, pertussis and influenza [3], [4], [5]) and a similar strategy may therefore prevent GBS disease. Capsular GBS vaccines have been in development since the 1990s [6], and a newer trivalent GBS polysaccharide-protein conjugate vaccine has completed phase-II evaluation in pregnant women [7]. The identification of serological correlates of protection against GBS disease is an important auxiliary tool for vaccine licensure [7]. Although maternal serotype-specific capsular antibody levels are associated with protection against invasive GBS disease in high-income settings [8], this association has not been assessed in low-middle income countries, nor has sero-correlates of protection been established. The aim of our study was therefore to determine a potential association between naturally acquired serotypes Ia and III GBS capsular antibody levels and invasive GBS disease in infants born at ≥34 weeks gestational age in a low-middle income setting.

Section snippets

Methods

We undertook a matched case-control study at three academic hospitals in Johannesburg, South Africa from November 2012 to February 2014. Although South Africa is classified as an upper-middle income country, the country has a high GINI coefficient and the majority of patients admitted to these public government-funded hospitals are from impoverished backgrounds typical of low-middle income settings [9]. The current incidence of GBS disease in our setting is approximately 2–3 per 1000 live

Results

Over a twelve month period, 122 (66 EOD and 56 LOD) infants were diagnosed with invasive GBS disease at the study sites. The clinical characteristics of these infants are reported elsewhere [12]. Sixty three (51.6%) cases were excluded from the analysis: 30 (24.6%) infants were <34 weeks gestation, blood samples were unavailable for 15 cases and only obtained >72 h in 2 infants after confirmation of disease, 13 infants had disease caused by serotypes other than Ia or III, 2 infants were

Discussion

This study describes an association between low capsular antibody concentrations and invasive GBS disease in South African infants from a low-middle income setting. Mothers whose infants developed serotype Ia or III invasive GBS disease had reduced antibody concentrations compared to homotypic controls, and we demonstrated that increased maternal antibody concentrations were associated with a reduced risk of invasive serotype Ia or III disease in the infant. Using the Bayesian model developed

Funding

ZD is funded in part by the Carnegie Corporation of New York (Grant number B8749) and the Discovery Foundation (Grant number 20289/1). SGL is funded in part by a career development award from the Medical Research Council of South Africa. SAM is funded in part by National Research Foundation/Department of Science and Technology: South African Research Chair Initiative in Vaccine Preventable Diseases and Medical Research Council of South Africa. The funders had no role in study design, data

Conflict of interest

All authors have no conflicts of interest relevant to this article to disclose

Acknowledgements

We are thankful to all participant mothers and infants in the study, RMPRU staff, and the registrars and consultants in the Departments of Clinical Microbiology and Infectious Diseases, Obstetrics and Gynaecology, and Pediatrics & Child Health at the three academic hospitals. We acknowledge Novartis Vaccines and Diagnostics (Italy) for providing the GBS antigens. We also acknowledge the Johannesburg Health District. We acknowledge funding from the Carnegie Corporation of New York (Grant number

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