Correlates of protection of serotype-specific capsular antibody and invasive Group B Streptococcus disease in South African infants
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
References (29)
- et al.
Group B streptococcal disease in infants aged younger than 3 months: systematic review and meta-analysis
Lancet
(2012) Assessments of vaccines for prenatal immunization
Vaccine
(2013)- et al.
Effectiveness of maternal pertussis vaccination in England: an observational study
Lancet
(2014) - et al.
Considerations for a phase-III trial to evaluate a group B Streptococcus polysaccharide-protein conjugate vaccine in pregnant women for the prevention of early- and late-onset invasive disease in young-infants
Vaccine
(2013) - et al.
Transplacental passage of IgG antibody to group B streptococcus serotype Ia
J Pediatr
(1984) - et al.
Variation in reported neonatal group B streptococcal disease incidence in developing countries
Clin Infect Dis
(2012) - et al.
Influenza vaccination of pregnant women and protection of their infants
N Engl J Med
(2014) - et al.
Immune response to type III group B streptococcal polysaccharide-tetanus toxoid conjugate vaccine
J Clin Invest
(1996) - et al.
Review on the association of Group B Streptococcus capsular antibody and protection against invasive disease in infants
Expert Rev Vaccines
(2015) - et al.
Health and health care in South Africa – 20 years after Mandela
N Engl J Med
(2014)