Bacterial and Host Determinants of Group B Streptococcal Vaginal Colonization and Ascending Infection in Pregnancy

Abstract

Group B streptococcus (GBS) is a gram-positive bacteria that asymptomatically colonizes the vaginal tract. However, during pregnancy maternal GBS colonization greatly predisposes the mother and baby to a wide range of adverse outcomes, including preterm birth (PTB), stillbirth, and neonatal infection. Although many mechanisms involved in GBS pathogenesis are partially elucidated, there is currently no approved GBS vaccine. The development of a safe and effective vaccine that can be administered during or prior to pregnancy remains a principal objective in the field, because current antibiotic-based therapeutic strategies do not eliminate all cases of invasive GBS infections. Herein, we review our understanding of GBS disease pathogenesis at the maternal-fetal interface with a focus on the bacterial virulence factors and host defenses that modulate the outcome of infection. We follow GBS along its path from an asymptomatic colonizer of the vagina to an invasive pathogen at the maternal-fetal interface, noting factors critical for vaginal colonization, ascending infection, and vertical transmission to the fetus. Finally, at each stage of infection we emphasize important host-pathogen interactions, which, if targeted therapeutically, may help to reduce the global burden of GBS.

Group B Streptococcal Colonization in African Countries: Prevalence, Capsular Serotypes, and Molecular Sequence Types

“…The CPS is a principal virulence factor in GBS [46,59]. Invasive GBS infections in neonates rely on the maternal antibody titer.…”

“…Clinical studies proved CPS-protein conjugates to be highly immunogenic. Thus, GBS 2021, 10, 1606 6 of 10 vaccine based on conjugating CPS to an immunogenic protein carrier is a well-studied vaccine approach [22,59]. Two protein conjugates are primarily used in GBS CPS-based vaccines: tetanus toxoid and the CRM197 diphtheria protein.…”

“…These include GBS6 as a hexavalent CPS CRM197 conjugate vaccine covering serotypes Ia, Ib, II, III, IV, and V. It has already completed Phase 1/2 clinical trials (Phase I/II: NCT03170609, Phase II: NCT04258995) [22,65] and is waiting to be tested in a Phase 2B trial that will evaluate GBS6 administered concomitantly with tetanus, diphtheria, and acellular pertussis vaccine (Tdap) (NCT04766086). Another candidate, GBS-NN/NN2, that reached Phase 2 clinical trials (phase II: NCT04596878) [59] is a protein-based vaccine. It contains a combination of two alpha protein fusions: GBS-NN and GBS-NN2.…”

Bacterial and Host Determinants of Group B Streptococcal Infection of the Neonate and Infant

“…GBS are typically commensal organisms and colonize the gastrointestinal (GI) and female lower reproductive tracts in approximately 20–25% of women ( Russell et al, 2017a ; Seale et al, 2017a ). Although its presence in these niches is generally asymptomatic, during pregnancy GBS can ascend from the lower genital tract into the uterus and infect the fetus ( Brokaw et al, 2021 ). An ascending GBS infection can cause invasive disease in the fetus, which is associated with a heightened risk for adverse pregnancy outcomes including preterm birth (PTB), stillbirth, and injury to fetal organs ( Santi et al, 2007 ; Verani et al, 2010 ; Adams Waldorf et al, 2011 ; McAdams et al, 2012 ; Ku et al, 2015 ; Bianchi-Jassir et al, 2017 ; Seale et al, 2017b ; Berardi et al, 2019 ; Ying et al, 2019 ; Brokaw et al, 2021 ; Horváth-Puhó et al, 2021 ; McCartney et al, 2021 ).…”

“…Although its presence in these niches is generally asymptomatic, during pregnancy GBS can ascend from the lower genital tract into the uterus and infect the fetus ( Brokaw et al, 2021 ). An ascending GBS infection can cause invasive disease in the fetus, which is associated with a heightened risk for adverse pregnancy outcomes including preterm birth (PTB), stillbirth, and injury to fetal organs ( Santi et al, 2007 ; Verani et al, 2010 ; Adams Waldorf et al, 2011 ; McAdams et al, 2012 ; Ku et al, 2015 ; Bianchi-Jassir et al, 2017 ; Seale et al, 2017b ; Berardi et al, 2019 ; Ying et al, 2019 ; Brokaw et al, 2021 ; Horváth-Puhó et al, 2021 ; McCartney et al, 2021 ). Early-onset disease (EOD) refers to invasive GBS disease presenting in the first week of life and are thought to result from acquisition of an invasive GBS infection either in utero or during birth through exposure to vaginal fluids; typically, these cases present with sepsis, but may also include pneumonia and/or meningitis in severe cases ( Figure 1 ).…”