Use of Type V Group B Streptococcal Conjugate Vaccine in Adults 65–85 Years Old

Palazzi, Debra L.; Rench, Marcia A.; Edwards, Morven S.; Baker, Carol J.

doi:10.1086/422010

Cited by 48 publications

(29 citation statements)

References 42 publications

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“…Since invasive GBS infection in elderly persons with underlying conditions has become an important problem, considerable effort has been made to develop an effective vaccine against GBS infection (40). Over 20 years, polysaccharide vaccines, conjugate vaccines, and protein-based vaccines have been developed to prevent neonatal GBS infection (11,38).…”

Section: Discussionmentioning

confidence: 99%

Molecular Characteristics of Group B Streptococci Isolated from Adults with Invasive Infections in Japan

et al. 2016

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bStreptococcus agalactiae (group B streptococcus) isolates (n ‫؍‬ 443) obtained from Japanese adults with invasive infections between April 2010 and March 2013 were analyzed for capsular serotype, multilocus sequence type (ST), antibiotic susceptibility, and resistance genes. Among these cases, bacteremia without primary focus was the most common variety of infection (49.9%), followed by cellulitis (12.9%) and pneumonia (9.0%). Concerning patient age (18 to 59, 60 to 69, 70 to 79, 80 to 89, and 90 years old or older), the incidence of pneumonia increased in patients in their 70s and 80s (P < 0.001), while younger patients (18 to 59 and 60 to 69 years old) were more likely to have abscesses (P < 0.05). The mortality rate was 10.2% for all ages. The most common capsular serotype was Ib (39.5%), followed by V (16.0%), III (13.8%), VI (9.5%), and Ia (8.6%). The main ST of serotype Ib strains was ST10, which belonged to clonal complex 10 (88.0%). The predominant clonal complexes of serotypes V and III, respectively, were 1 (78.9%) and 19 (75.4%). Among these isolates, 9 strains (2.0%) were identified as group B streptococci with reduced penicillin susceptibility, reflecting amino acid substitutions in penicillin-binding protein 2X (PBP2X). In addition, 19.2% of all strains possessed mef(A/E), erm(A), or erm(B) genes, which mediate macrolide resistance, while 40.2% of strains were resistant to quinolones resulting from amino acid substitutions in GyrA and ParC. Our data argue strongly for the continuous surveillance of microbial characteristics and judicious antibiotic use in clinical practice.

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Section: Discussionmentioning

confidence: 99%

Molecular Characteristics of Group B Streptococci Isolated from Adults with Invasive Infections in Japan

et al. 2016

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“…In this fashion, the Sia-expressing bacterial pathogens could simultaneously interfere with complement and cellular components of innate immunity. In the particular case of GBS, clinical disease is seen in the neonate and other special populations, including pregnant women, the elderly, and diabetics (13,28). Future studies could examine both the patterns of hCD33rSiglec expression and the cellular responses mediated by these receptors in these populations for correlations with increased susceptibility to GBS infection.…”

Section: Vol 189 2007 Gbs Sialic Acid and Host Siglecs 1235mentioning

confidence: 99%

Group B Streptococcal Capsular Sialic Acids Interact with Siglecs (Immunoglobulin-Like Lectins) on Human Leukocytes

Carlin

Lewis

Varki³

et al. 2007

J Bacteriol

155

114

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Group B Streptococcus (GBS) is classified into nine serotypes that vary in capsular polysaccharide (CPS)architecture but share in common the presence of a terminal sialic acid (Sia) residue. This position and linkage of GBS Sia closely resembles that of cell surface glycans found abundantly on human cells. CD33-related Siglecs (CD33rSiglecs) are a family of Sia-binding lectins expressed on host leukocytes that engage host Sia-capped glycans and send signals that dampen inflammatory gene activation. We hypothesized that GBS evolved to display CPS Sia as a form of molecular mimicry limiting the activation of an effective innate immune response. In this study, we applied a panel of immunologic and cell-based assays to demonstrate that GBS of several serotypes interacts in a Sia-and serotype-specific manner with certain human CD33rSiglecs, including hSiglec-9 and hSiglec-5 expressed on neutrophils and monocytes. Modification of GBS CPS Sia by O acetylation has recently been recognized, and we further show that the degree of O acetylation can markedly affect the interaction between GBS and hSiglec-5, -7, and -9. Thus, production of Sia-capped bacterial polysaccharide capsules that mimic human cell surface glycans in order to engage CD33rSiglecs may be an example of a previously unrecognized bacterial mechanism of leukocyte manipulation.Group B Streptococcus (GBS) is the leading cause of bacterial pneumonia, sepsis, and meningitis in human newborns and is increasingly recognized as a pathogen in adult populations, including diabetics, pregnant women, and the elderly. A critical factor contributing to GBS virulence is its surface capsular polysaccharide (CPS). The CPS forms the outermost layer of the bacterial surface and is typically composed of repeating subunits of four monosaccharides, i.e., glucose, galactose, N-acetylglucosamine, and N-acetylneuraminic acid, polymerized in serotype-specific configurations (10). GBS isolates are categorized as belonging to one of nine different serotypes (Ia, Ib, and II to VIII) based on antibody recognition. Although the physical structure of the CPS of each GBS serotype is unique, all GBS serotypes invariably share a terminal ␣2,3-linked N-acetylneuraminic acid (Neu5Ac), which is identical to the predominant sialic acid (Sia) found on human cells. It has recently been discovered that GBS modify its CPS Sia by addition of a single O-acetyl group at the seventh carbon position that can subsequently migrate to the eighth or ninth carbon position (23,24). GBS synthesizes and modifies Sia by using a de novo pathway in which four genes, neuA to neuD, are responsible for Sia synthesis and O acetylation, while cpsK mediates transfer of Sia to the CPS subunit (9,15,23,31,32).The Sia-recognizing immunoglobulin (Ig) superfamily lectins (Siglecs) are a family of structurally related type I transmembrane proteins composed of one unique (or two in the case of Siglec-XII) V-set Ig domain responsible for recognizing sialylated glycoconjugates, followed by a variable number of structural C2-set ...

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“…A phase 1 study has documented the safety and immunogenicity of type V GBS CPS-TT conjugate vaccine (V-TT) in 32 healthy adults 65 to 85 years of age who were randomized to receive a single intramuscular dose of V-TT (n = 22) or licensed tetanus-diphtheria toxoid vaccine (n = 11). 38 Capsular polysaccharide type V is a common type causing invasive GBS disease in nonpregnant adults. 39 The substantial, and increasing, disease burden from GBS and the efficacy of unconjugated pneumococcal vaccine for reducing the disease burden due to Streptococcus pneumoniae in adults in the US suggest that nonpregnant adults might provide a feasible population for efficacy testing of a candidate GBS conjugate vaccine.…”

confidence: 99%

Group B streptococcal conjugate vaccine: A timely concept for which the time has come

Edwards¹

2008

Human Vaccines

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Use of Type V Group B Streptococcal Conjugate Vaccine in Adults 65–85 Years Old

Cited by 48 publications

References 42 publications

Molecular Characteristics of Group B Streptococci Isolated from Adults with Invasive Infections in Japan

Molecular Characteristics of Group B Streptococci Isolated from Adults with Invasive Infections in Japan

Group B Streptococcal Capsular Sialic Acids Interact with Siglecs (Immunoglobulin-Like Lectins) on Human Leukocytes

Group B streptococcal conjugate vaccine: A timely concept for which the time has come

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