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Surface Structures of Group B Important in Human Immunity

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  • Authors: Lawrence C. Paoletti1, Dennis L. Kasper2
  • Editors: Vincent A. Fischetti3, Richard P. Novick4, Joseph J. Ferretti5, Daniel A. Portnoy6, Miriam Braunstein7, Julian I. Rood8
  • VIEW AFFILIATIONS HIDE AFFILIATIONS
    Affiliations: 1: Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115; 2: Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115; 3: The Rockefeller University, New York, NY; 4: Skirball Institute for Molecular Medicine, NYU Medical Center, New York, NY; 5: Department of Microbiology & Immunology, University of Oklahoma Health Science Center, Oklahoma City, OK; 6: Department of Molecular and Cellular Microbiology, University of California, Berkeley, Berkeley, CA; 7: Department of Microbiology and Immunology, University of North Carolina-Chapel Hill, Chapel Hill, NC; 8: Infection and Immunity Program, Monash Biomedicine Discovery Institute, Monash University, Melbourne, Australia
  • Source: microbiolspec March 2019 vol. 7 no. 2 doi:10.1128/microbiolspec.GPP3-0001-2017
  • Received 07 September 2018 Accepted 15 November 2018 Published 15 March 2019
  • Lawrence C. Paoletti, [email protected]
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  • Abstract:

    The surface of the Gram-positive opportunistic pathogen Streptococcus agalactiae, or group B Streptococcus (GBS), harbors several carbohydrate and protein antigens with the potential to be effective vaccines. Capsular polysaccharides of all clinically-relevant GBS serotypes coupled to immunogenic proteins of both GBS and non-GBS origin have undergone extensive testing in animals that led to advanced clinical trials in healthy adult women. In addition, GBS proteins either alone or in combination have been tested in animals; a fusion protein construct has recently advanced to human clinical studies. Given our current understanding of the antigenicity and immunogenicity of the wide array of GBS surface antigens, formulations now exist for the generation of viable vaccines against diseases caused by GBS.

  • Citation: Paoletti L, Kasper D. 2019. Surface Structures of Group B Important in Human Immunity. Microbiol Spectrum 7(2):GPP3-0001-2017. doi:10.1128/microbiolspec.GPP3-0001-2017.

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/content/journal/microbiolspec/10.1128/microbiolspec.GPP3-0001-2017
2019-03-15
2019-08-21

Abstract:

The surface of the Gram-positive opportunistic pathogen Streptococcus agalactiae, or group B Streptococcus (GBS), harbors several carbohydrate and protein antigens with the potential to be effective vaccines. Capsular polysaccharides of all clinically-relevant GBS serotypes coupled to immunogenic proteins of both GBS and non-GBS origin have undergone extensive testing in animals that led to advanced clinical trials in healthy adult women. In addition, GBS proteins either alone or in combination have been tested in animals; a fusion protein construct has recently advanced to human clinical studies. Given our current understanding of the antigenicity and immunogenicity of the wide array of GBS surface antigens, formulations now exist for the generation of viable vaccines against diseases caused by GBS.

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Figures

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FIGURE 1

Proposed structure of the streptococcal group B carbohydrate, as modified from reference 15 . The group B carbohydrate is linked to -acetylmuramic acid of the cell wall ( 162 ).

Source: microbiolspec March 2019 vol. 7 no. 2 doi:10.1128/microbiolspec.GPP3-0001-2017
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Image of FIGURE 2
FIGURE 2

Electron micrographs of immunogold-labeled GBS showing surface localization of CPS, a protein antigen, and pili. Bars, 500 nm. (Upper left) CPS of GBS type Ia strain A909 was visualized after incubation with rabbit antiserum to the CPS followed by 20-nm-diameter gold-labeled protein A. (Upper right) The alpha C protein of GBS A909 was visualized after incubation with rabbit antiserum to the purified one-repeat alpha C protein followed by 15-nm-diameter gold-labeled protein A. Both upper images are reproduced from ( 163 ) with permission. (Bottom) Pilus structures of GBS type VIII strain JM9130013 were visualized with immunogold labeling using GBS80 antisera. The bottom image is reproduced with permission from ( 121 ).

Source: microbiolspec March 2019 vol. 7 no. 2 doi:10.1128/microbiolspec.GPP3-0001-2017
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FIGURE 3

Chair models of the repeating units of GBS capsular polysaccharides.

Source: microbiolspec March 2019 vol. 7 no. 2 doi:10.1128/microbiolspec.GPP3-0001-2017
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FIGURE 4

(Top) Schematic of gene clusters in nine GBS serotypes. Conserved genes are depicted by white arrows; variable genes are depicted by black arrows. The variable gap in the center of the clusters was introduced to permit alignment of homologous genes ( 60 ). (Bottom) Hypothetical genetic relationship between CPSs of serotypes V, VII, and (newly described) IX. Reproduced with permission from the ( 41 ).

Source: microbiolspec March 2019 vol. 7 no. 2 doi:10.1128/microbiolspec.GPP3-0001-2017
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FIGURE 5

Pilus islands (PI)-1 , PI-2a , and PI-2b of GBS: conservation of pilus island genes among 186 GBS clinical isolates. Sortase genes (gray arrows) are sequences with identity of 100% (same color) or <90% (different colors). Vertical bars are single mutations. The number above each vertical bar indicates the position or substitution of the mutated residue. Reproduced with permission from the ( 122 ).

Source: microbiolspec March 2019 vol. 7 no. 2 doi:10.1128/microbiolspec.GPP3-0001-2017
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FIGURE 6

Mouse models of GBS disease. The immunogenicity and efficacy of GBS vaccines have been evaluated with the maternal vaccination-neonatal mouse model (top timeline) by actively vaccinating female mice, mating these mice, and subsequently challenging their offspring with GBS. In a passive vaccination-protection model (bottom timeline), newborn pups born to dams that received immune sera during pregnancy are challenged with GBS as a means of measuring the functional capacity of IgG. The therapeutic potential of GBS vaccine-induced antiserum (middle timeline) has been ascertained by inoculating naive pups with GBS 4 h before administration of immune serum. In all three models, pups are infected or challenged with GBS within 24 to 48 h of birth, and survival is assessed 48 h after challenge. Active vaccination of adult mice followed by an intraperitoneal challenge with viable GBS several weeks later has also been used to evaluate vaccines.

Source: microbiolspec March 2019 vol. 7 no. 2 doi:10.1128/microbiolspec.GPP3-0001-2017
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Tables

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TABLE 1

GBS proteins evaluated as protective antigens

Source: microbiolspec March 2019 vol. 7 no. 2 doi:10.1128/microbiolspec.GPP3-0001-2017
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TABLE 2

Characteristics of GBS conjugate vaccines

Source: microbiolspec March 2019 vol. 7 no. 2 doi:10.1128/microbiolspec.GPP3-0001-2017

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