SIgA, TGF-beta 1, IL-10, and TNF alpha in Colostrum Are Associated with Infant Group B Streptococcus Colonization

Background: Group B Streptococcus (GBS) is a major cause of mortality and morbidity in infants and is associated with transmission from a colonized mother at birth and via infected breastmilk. Although maternal/infant colonization with GBS is common, the majority of infants exposed to GBS remain unaffected. The association between breastmilk immune factors and infant colonization and disease prevention has not been elucidated. Objectives: We have investigated the association between SIgA and cytokines in breastmilk and infant GBS colonization and clearance. Methods: Mother/infant GBS colonization was determined in a prospective cohort of 750 Gambian mother/infant pairs followed to day 89 of life. Anti-GBS secretory IgA bound to the surface of whole bacteria was assessed by flow cytometry and a panel of 12 cytokines quantified by mesoscale discovery in colostrum, breastmilk and serum. Results: Compared with infants receiving low anti-GBS SIgA in colostrum, infants receiving high anti-GBS SIgA were at decreased risk of GBS colonization for serotypes III and V. Infants colonized at day 6 were twice as likely to receive colostrum with high TGF-β1, TNFα, IL10, and IL-6 compared to uncolonized infants. Infants receiving high colostral TGF-β1, TNFα, and IL-6 had two-fold enhanced GBS clearance between birth and day 89. Conclusion: Our results suggest that the infant GBS colonization risk diminishes with increasing anti-GBS SIgA antibody in breastmilk and that key maternally derived cytokines might contribute to protection against infant colonization. These findings might be leveraged to develop interventions including maternal vaccination that may reduce infant GBS colonization

Immune Modulation by Adjuvants Combined with Diphtheria Toxoid Administered Topically in BALB/c Mice After Microneedle Array Pretreatment

Purpose. In this study, modulation of the immune response against diphtheria toxoid (DT) by various adjuvants in transcutaneous immunization (TCI) with microneedle array pretreatment was investigated. Methods. TCI was performed on BALB/c mice with or without microneedle array pretreatment using DT as a model antigen co-administrated with lipopolysaccharide (LPS), Quil A, CpG oligo deoxynucleotide (CpG) or cholera toxin (CT) as adjuvant. The immunogenicity was evaluated by measuring serum IgG subtype titers and neutralizing antibody titers. Results. TCI with microneedle array pretreatment resulted in a 1,000-fold increase of DT-specific serum IgG levels as compared to TCI. The immune response was further improved by co-administration of adjuvants, showing a progressive increase in serum IgG titers when adjuvanted with LPS, Quil A, CpG and CT. IgG titers of the CT-adjuvanted group reached levels comparable to those obtained after DTalum subcutaneous injection. The IgG1/IgG2a ratio of DT-specific antibodies decreased in the following sequence: plain DT, Quil A, CT and CpG, suggesting that the immune response was skewed towards the Th1 direction. Conclusions. The potency and the quality of the immune response against DT administered by microneedle array mediated TCI can be modulated by co-administration of adjuvants. KEY WORDS: cholera toxin; CpG; diphtheria toxoid; microneedle array; transcutaneous immunization