Group B Streptococcus (GBS) colonization is dynamic over time, whilst GBS capsular polysaccharides-specific antibody remains stable

Abstract

Group B Streptococcus (GBS) is a leading cause of adverse pregnancy outcomes due to invasive infection. This study investigated longitudinal variation in GBS rectovaginal colonization, serum and vaginal GBS capsular polysaccharide (CPS)-specific antibody levels. Non-pregnant women were recruited in the UK and were sampled every 2 weeks over a 12-week period. GBS isolates were taken from recto-vaginal swabs and serotyped by polymerase chain reaction. Serum and vaginal immunoglobulin G (IgG) and nasal immunoglobulin A (IgA) specific to CPS were measured by Luminex, and total IgG/A by ELISA. Seventy women were enrolled, of median age 26. Out of the 66 participants who completed at least three visits: 14/47 (29.8%) women that were GBS negative at screening became positive in follow-up visits and 16/19 (84.2%) women who were GBS positive at screening became negative. There was 50% probability of becoming negative 36 days after the first positive swab. The rate of detectable GBS carriage fluctuated over time, although serum, vaginal, and nasal CPS-specific antibody levels remained constant. Levels of CPS-specific antibodies were higher in the serum of individuals colonized with GBS than in non-colonized, but similar in the vaginal and nasal mucosa. We found correlations between antibody levels in serum and the vaginal and nasal mucosa. Our study demonstrates the feasibility of elution methods to retrieve vaginal and nasal antibodies, and the optimization of immunoassays to measure GBS-CPS-specific antibodies. The difference between the dynamics of colonization and antibody response is interesting and further investigation is required for vaccine development.

Trial registration: ClinicalTrials.gov NCT04059510.

Keywords: GBS vaccine; capsular-polysaccharides-specific antibodies; colonization; group B Streptococcus; mucosal immunity; neonatal infection.

© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Immunology.

Figures

Graphical Abstract

Figure 1:

flow of participants through study. LTFU: lost to follow-up; GUTI: genitourinary infection.

Figure 2:

proportion of GBS serotypes, by visit, detected by rectal and vaginal swabs. Percent serotype calculated using the total number of isolates at each visit as the denominator.

Figure 3:

estimated time before rectovaginal GBS clearance. Estimated with the Kaplan-Meier method, including 95% confidence bands. Time from the first positive to the first negative swab (A), and time from the first positive swab to clearance until the end of the study (B). The upper bound of IQR in the right-hand panel is out of data range and not computable.

Figure 4:

timecourse of CPS-specific antibody levels. CPS-specific IgG levels were measured in serum (A) and vaginal secretions (B), and IgA in nasal samples (C) over the 3 months of the study. Serum was collected on weeks 0, 6, and 12. Vaginal secretions were collected every 2 weeks. Nasal samples were collected on weeks 0 and 12. The concentration of GBS CPS-specific antibodies were measured at each time point. Concentrations on log scale. Each line represents an individual. Medians and quartiles are plotted.

Figure 5:

CPS-specific antibodies between colonized (C) and non-colonized (NC) individuals in serum and nasal and vaginal mucosa. An individual was defined as colonized with a serotype if they carried this serotype at one or more visits. Concentrations plotted are, for each individual, the average concentrations between all visits. Medians compared with a Mann-Whitney test in serum (A), vaginal (B), and nasal samples (C), concentration on log scale. Fold change in serum (D), vaginal (E), and nasal samples (F) was calculated between levels measured in the last collected sample over the first collected sample for each individual. Concentrations of serum CPS-specific IgG in µg/ml, of vaginal CPS-specific IgG/total IgG in ‰ and of nasal CPS-specific IgA/total IgA in AU.

Figure 6:

colonization status and CPS-specific antibody levels. Average concentrations between all visits, only concentrations above the assay limit of quantification of 0.1 µg/ml are displayed. A: Colonized individuals with homologous antibodies. B: Colonized individuals with GBS CPS-specific antibodies for heterologous serotypes. C: Non-colonized individuals with GBS CPS-specific antibodies.

Figure 7:

correlation between CPS-specific antibody concentrations in serum, vaginal secretions, and nasal samples. Spearman correlation coefficient are respectively, between serum and vaginal secretions: r = 0.61 (n = 32), between vaginal secretions and nasal samples: r = 0.76 (n = 8), and between serum and nasal samples: r = 0.45 (n = 37).

Figure 8:

proportion of colonizing serotypes (A), and proportions of CPS-specific antibodies in serum (B) and vaginal (C) and nasal mucosa (D). An individual was defined as colonized or as having serotype-specific antibody if detection occurred at least once during study visits. Some individuals carried multiple serotypes and had multiple different CPS-specific antibodies detected. The denominator for proportions is the total number of women who were colonized (A) or with detected antibody by site (B, C, D).