Mucosal vaccination promotes clearance of Streptococcus agalactiae vaginal colonization

Jacqueline A Baker,Emma L Lewis,Leah M Byland,Maryam Bonakdar,Tara M Randis,Adam J Ratner

doi:10.1016/j.vaccine.2017.01.029

Jacqueline A Baker, Emma L Lewis + Show 4 more

Open Access

https://doi.org/10.1016/j.vaccine.2017.01.029

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Journal: Vaccine	Publication Date: Feb 2, 2017
Citations: 27	License type: cc-by

Affiliation: Columbia University, New York University

Abstract

Group B Streptococcus (GBS) is a leading cause of morbidity and mortality in infants, and colonization of the maternal genital tract is the primary risk factor for newborn infection. Despite the importance of mucosal colonization in GBS pathogenesis, relevant host and bacterial factors are incompletely understood. We investigated the role of humoral immunity in clearance of vaginal colonization in vivo. B-cell-deficient mice or those lacking neonatal Fc-receptor, a mediator of IgG transport to the vaginal mucosa, exhibit prolonged GBS vaginal colonization compared to wild type animals. Intranasal but not intramuscular immunization induced systemic and mucosal immune responses and decreased GBS colonization duration without altering initial colonization density. Vaccine-induced clearance of GBS was serotype-specific, suggesting a role for anti-capsule antibodies in protection. Our results support a role for humoral immunity in GBS eradication from the female genital tract and suggest that mucosal vaccination may prime colonization clearance.

Highlights

Group B Streptococcus (GBS; Streptococcus agalactiae) can be transmitted to the newborn via mucosal exposure during parturition, or to the fetus via ascension of the organism from the vagina to the placenta or amniotic fluid
Humoral immunity contributes to clearance of GBS vaginal colonization in vivo We sought to determine the role of humoral immunity in the maintenance of GBS colonization [16]
We investigated the contribution of humoral immunity to the clearance of GBS colonization and to investigate the role of immunization in colonization clearance

Summary

INTRODUCTION

Group B Streptococcus (GBS; Streptococcus agalactiae) can be transmitted to the newborn via mucosal exposure during parturition, or to the fetus via ascension of the organism from the vagina to the placenta or amniotic fluid. Clinical guidelines advocate GBS screening at 35–37 weeks gestation with intrapartum antibiotic prophylaxis (IAP) for colonized women [2]. These efforts have decreased early–onset (EO) GBS disease rates by 80% [3]. Immune mechanisms of GBS colonization clearance are incompletely understood. Clinical studies suggest that serotype-specific immune responses may follow asymptomatic colonization [8,9,10] and may mediate protection against disease or colonization. We demonstrate that mice lacking either antibody production (μMT) or FcRn have a defect in clearance of GBS from the vagina and that mucosal immunization primes clearance of colonization

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FUNDING INFORMATION