Maternal vaccination with a type-III glycoconjugate protects mouse neonates against Group B Streptococcus intranasal infection

Emiliano Chiarot,Immaculada Margarit Y Ros,Giuliano Bensi,Eleonora Naimo,Patrizia Giannetti,Alessia Corrado

doi:10.1038/s41598-021-00941-z

Emiliano Chiarot, Immaculada Margarit Y Ros + Show 4 more

Open Access

https://doi.org/10.1038/s41598-021-00941-z

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Abstract

Group B Streptococcus (GBS) is generally an asymptomatic colonizer of human mucosa but it occasionally infects pregnant women and neonates through vertical transmission, causing disease during the first weeks of life with frequent and severe complications. Preclinical studies have shown that maternal vaccination with polysaccharide-based vaccines protects mothers and offspring from GBS mucosal colonization and consecutive infection. In these models, bacteria were inoculated in mouse either intravaginally in the last trimester of pregnancy or systemically in pups. Here, we investigated whether maternal vaccination with glycoconjugate vaccines may also prevent GBS-mediated colonization and disease in neonates using an infection route that more closely mimics inhalation or ingestion of bacteria during human delivery. To address this point, mice aged less than two days were intranasally challenged with epidemiologically relevant GBS strains. Bacteria were found to colonize nose and intestine, reaching in some cases lungs and blood during the first days of life. Bacteria were also found in vagina of a fraction of colonized female mice within the first month of life. GBS-specific IgG induced by maternal vaccination with a glycoconjugate vaccine formulation were found in blood and mucosal tissues of newborns. Finally, when intranasally challenged with GBS serotype III strains, pups delivered by vaccinated mothers were partially protected against mucosal colonization and deeper infection.

Highlights

Group B Streptococcus (GBS) is normally an asymptomatic member of the vaginal mucosa and lower gastrointestinal tract in up to 30% of pregnant women, but is able to infect mothers, fetuses in utero and neonates, most likely by inhalation or/and ingestion of bacteria occurring during d elivery[1,2,3]
We have developed a model of intranasal infection by bacterial inhalation in mouse neonates and we have followed bacterial spreading in several organs and tissues
Inhalation of bacteria during delivery has been recognized as the preferred route of early onset disease (EOD) infection in human n eonates[25]

Summary

Introduction

Group B Streptococcus (GBS) is normally an asymptomatic member of the vaginal mucosa and lower gastrointestinal tract in up to 30% of pregnant women, but is able to infect mothers, fetuses in utero and neonates, most likely by inhalation or/and ingestion of bacteria occurring during d elivery[1,2,3]. When the symptoms occur within one week postdelivery it is defined as early onset disease (EOD) and as late onset disease (LOD) if later Mucosal colonization, both in mothers and offspring, is considered one of the main risk factors for infection[6,7,8,9,10,11]. Preclinical models of GBS infection showed that these glycoconjugates could prevent maternal and offspring disease and reduce mucosal bacterial carriage[23,24] In these models, bacteria were inoculated intravaginally in pregnant mice a few days before delivery or intraperitoneally in newborns, leaving open the question whether the vaccine.

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