Alpha C protein-specific immunity in humans with group B streptococcal colonization and invasive disease

Pannaraj, Pia S.; Kelly, Joanna K.; Rench, Marcia A.; Madoff, Lawrence C.; Edwards, Morven S.; Baker, Carol J.

doi:10.1016/j.vaccine.2007.11.034

Cited by 16 publications

(5 citation statements)

References 32 publications

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“…This is associated with increased susceptibility to opsonophagocytic antibody-mediated killing as compared to the GBS isolated previously from the respective newborn infant with sepsis ( 67 ). In line with these observations, low tandem repeat expression during infections seems to impair the specific antibody response and antibody-mediated killing ( 61 , 64 , 65 , 68 , 69 ). Furthermore, GBS alpha C proteins can promote invasion of human epithelial cells via α1β1-integrin binding ( 66 ).…”

Section: The Pathogen Site: Gbs Virulence Strategies To Progress Fromsupporting

confidence: 57%

Interaction of Streptococcus agalactiae and Cellular Innate Immunity in Colonization and Disease

Landwehr-Kenzel

Henneke

2014

Front. Immunol.

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Streptococcus agalactiae (Group B streptococcus, GBS) is highly adapted to humans, where it is a normal constituent of the intestinal and vaginal flora. Yet, GBS has highly invasive potential and causes excessive inflammation, sepsis, and death at the beginning of life, in the elderly and in diabetic patients. Thus, GBS is a model pathobiont that thrives in the healthy host, but has not lost its potential virulence during coevolution with mankind. It remains incompletely understood how the innate immune system contains GBS in the natural niches, the intestinal and genital tracts, and which molecular events underlie breakdown of mucocutaneous resistance. Newborn infants between days 7 and 90 of life are at risk of a particularly striking sepsis manifestation (late-onset disease), where the transition from colonization to invasion and dissemination, and thus from health to severe sepsis is typically fulminant and not predictable. The great majority of late-onset sepsis cases are caused by one clone, GBS ST17, which expresses HvgA as a signature virulence factor and adhesin. In mice, HvgA promotes the crossing of both the mucosal and the blood–brain barrier. Expression levels of HvgA and other GBS virulence factors, such as pili and toxins, are regulated by the upstream two-component control system CovR/S. This in turn is modulated by acidic epithelial pH, high glucose levels, and during the passage through the mouse intestine. After invasion, GBS has the ability to subvert innate immunity by mechanisms like glycerinaldehyde-3-phosphate-dehydrogenase-dependent induction of IL-10 and β-protein binding to the inhibitory phagocyte receptors sialic acid binding immunoglobulin-like lectin 5 and 14. On the host side, sensing of GBS nucleic acids and lipopeptides by both Toll-like receptors and the inflammasome appears to be critical for host resistance against GBS. Yet, comprehensive models on the interplay between GBS and human immune cells at the colonizing site are just emerging.

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Section: The Pathogen Site: Gbs Virulence Strategies To Progress Fromsupporting

confidence: 57%

Interaction of Streptococcus agalactiae and Cellular Innate Immunity in Colonization and Disease

Landwehr-Kenzel

Henneke

2014

Front. Immunol.

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“…Sero-epidemiological studies showed some evidence in favor of an association between low maternal GBS CPS specific IgG levels and the risk of GBS disease in offspring. Associations between maternal GBS surface-protein antibody concentrations and invasive disease in their infants have not been as clearly established: among the surface proteins studied so far (surface immunogenic protein [Sip], resistance to proteases immunity group B [Rib], AlphaC protein, BetaC protein, fibrinogen-binding protein A, GBS-immunogenic bacterial adhesion, and pilus-island surface protein antibodies), limited data suggest that antibodies against alphaC and Rib proteins may provide protection against invasive neonatal GBS disease 258 , 261 – 265 .…”

Section: Gbs Vaccine Developmentmentioning

confidence: 99%

Group B Streptococcus vaccine development: present status and future considerations, with emphasis on perspectives for low and middle income countries

et al. 2016

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Globally, group B Streptococcus (GBS) remains the leading cause of sepsis and meningitis in young infants, with its greatest burden in the first 90 days of life. Intrapartum antibiotic prophylaxis (IAP) for women at risk of transmitting GBS to their newborns has been effective in reducing, but not eliminating, the young infant GBS disease burden in many high income countries. However, identification of women at risk and administration of IAP is very difficult in many low and middle income country (LMIC) settings, and is not possible for home deliveries. Immunization of pregnant women with a GBS vaccine represents an alternate pathway to protecting newborns from GBS disease, through the transplacental antibody transfer to the fetus in utero. This approach to prevent GBS disease in young infants is currently under development, and is approaching late stage clinical evaluation. This manuscript includes a review of the natural history of the disease, global disease burden estimates, diagnosis and existing control options in different settings, the biological rationale for a vaccine including previous supportive studies, analysis of current candidates in development, possible correlates of protection and current status of immunogenicity assays. Future potential vaccine development pathways to licensure and use in LMICs, trial design and implementation options are discussed, with the objective to provide a basis for reflection, rather than recommendations.

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“…Furthermore, studies have demonstrated that conjugating CPS to GBS surface proteins results in serotype-independent protection 25 – 27 . Also, natural induced α-C protein antibodies from pregnant women were shown to be capable of inducing opsonophagocytic killing 28 . Fabbrini et al .…”

Section: Introductionmentioning

confidence: 99%

Association between antibodies against group B Streptococcus surface proteins and recto-vaginal colonisation during pregnancy

Dzanibe

Kwatra

Adrian

et al. 2017

Sci Rep

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Group B Streptococcus (GBS) recto-vaginal colonisation in pregnant women is the major risk factor for early-onset invasive GBS disease in their newborns. We aimed to determine the association between serum antibody levels against 11 GBS surface proteins and recto-vaginal acquisition of GBS colonisation during pregnancy. Sera collected from pregnant women at 20–25 weeks and ≥37 weeks of gestation age were measured for IgG titres against GBS surface proteins using a multiplex immunoassay. Women were evaluated for recto-vaginal colonisation every 4–5 weeks. We observed that the likelihood of becoming colonised with GBS during pregnancy was lower in women with IgG titres ≥200 U/mL against gbs0233 (adjusted OR = 0.47 [95% CI: 0.25–0.89], p = 0.021) and ≥85 U/mL for gbs1539 (adjusted OR = 0.44 [95% CI: 0.24–0.82], p = 0.01) when comparing between women who acquired GBS colonisation and those that remained free of GBS colonisation throughout pregnancy. IgG titres (U/mL) specific to BibA and Sip were higher in pregnant women colonised with GBS (380.19 and 223.87, respectively) compared to women with negative GBS cultures (234.42 and 186.21, respectively; p < 0.01) at ≥37 weeks gestation. Antibodies induced by gbs0233 and gbs1539 were associated with a reduced likelihood of recto-vaginal GBS acquisition during pregnancy and warrant further investigation as vaccine targets.

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Alpha C protein-specific immunity in humans with group B streptococcal colonization and invasive disease

Cited by 16 publications

References 32 publications

Interaction of Streptococcus agalactiae and Cellular Innate Immunity in Colonization and Disease

Interaction of Streptococcus agalactiae and Cellular Innate Immunity in Colonization and Disease

Group B Streptococcus vaccine development: present status and future considerations, with emphasis on perspectives for low and middle income countries

Association between antibodies against group B Streptococcus surface proteins and recto-vaginal colonisation during pregnancy

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