Opsonophagocytic Antibodies to Serotype Ia, Ib, and III Group B Streptococcus among Korean Infants and in Intravenous Immunoglobulin Products

Abstract

Group B streptococcus (GBS) infection is a leading cause of sepsis and meningitis among infants, and is associated with high rates of morbidity and mortality in many countries. Protection against GBS typically involves antibody-mediated opsonization by phagocytes and complement components. The present study evaluated serotype-specific functional antibodies to GBS among Korean infants and in intravenous immunoglobulin (IVIG) products. An opsonophagocytic killing assay (OPA) was used to calculate the opsonization indices (OIs) of functional antibodies to serotypes Ia, Ib, and III in 19 IVIG products from 5 international manufacturers and among 98 Korean infants (age: 0-11 months). The GBS Ia, Ib, and III serotypes were selected because they are included in a trivalent GBS vaccine formulation that is being developed. The OI values for the IVIG products were 635-5,706 (serotype Ia), 488-1,421 (serotype Ib), and 962-3,315 (serotype III), and none of the IVIG lots exhibited undetectable OI values (< 4). The geometric mean OI values were similar for all 3 serotypes when we compared the Korean manufacturers. The seropositive rate among infants was significantly lower for serotype Ia (18.4%), compared to serotype Ib and serotype III (both, 38.8%). Infant age of ≥ 3 months was positively correlated with the seropositive rates for each serotype. Therefore, only a limited proportion of infants exhibited protective immunity against serotype Ia, Ib, and III GBS infections. IVIG products that exhibit high antibody titers may be a useful therapeutic or preventive measure for infants. Further studies are needed to evaluate additional serotypes and age groups.

Keywords: Antibodies; Immunoglobulins; Infant; Intravenous; Opsonin Proteins; Streptococcus agalactiae.

Fig. 1

Microcolonies of serotype III GBS on a THYA-NR plate (Todd-Hewitt agar with yeast extract containing neutral red and Tris solution) after overnight incubation (37°C/5% CO₂) and incubation for 4–5 hours at room temperature/room air. The numbers of surviving colonies were counted on the plates. The average diameter of the microcolonies was approximately 0.3 mm, and the colonies were clearly red and spatially separated. GBS = group B streptococcus.

Fig. 2

OIs for GBS according to serotype (Ia, Ib, and III) in various IVIG products (n = 19). The top bar is the highest value, the bottom bar is the lowest value, the top of the box indicates the third quartile, the bottom of the box indicates the first quartile, and the middle bar is the median value. The lower limit of detection for the opsonization index was 4. The numbers of lots are given in parentheses. OIs = opsonization indices, GBS = group B streptococcus, IVIG = intravenous immunoglobulin.

Fig. 3

OIs for GBS according to serotype (Ia, Ib, and III) and age among Korean infants (n = 98). The lower limit of detection for the opsonization index was 4. The numbers of individuals in each age group are given in parentheses. OIs = opsonization indices, GBS = group B streptococcus.