Titre du document / Document title

Recombinant group b streptococcus beta C protein and a variant with the deletion of its immunoglobulin A-binding site are protective mouse maternal vaccines and effective carriers in conjugate vaccines

Auteur(s) / Author(s)

YANG Hsiao-Hui ⁽¹⁾ ; MADOFF Lawrence C. ⁽¹⁾ ; GUTTORMSEN Hilde-Kari ⁽¹⁾ ; LIU Yong-Dong ⁽¹⁾ ; PAOLETTI Lawrence C. ⁽¹⁾ ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

⁽¹⁾ Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, ETATS-UNIS

Résumé / Abstract

Immunogenic vaccines against group B Streptococcus (GBS) have been created by coupling the GBS capsular polysaccharides (CPS) to carrier proteins. The GBS beta C protein (BCP) serves as an effective carrier while inducing protective immunity against BCP-expressing strains. BCP also binds human immunoglobulin A (IgA), a characteristic that may be undesirable for use in humans. Here, we examined the immunogenicity and protective efficacy of a recombinant GBS BCP (rBCP), an rBCP modified to eliminate its IgA-binding site (rBCP^∇IgA), and their corresponding GBS serotype III CPS conjugates (III-rBCP and III-rBCP^∇IgA). Deletion of the IgA-binding site or conjugation to CPS did not alter antigenic BCP epitopes. Recombinant proteins and conjugates elicited specific, high-titered IgG in mice. Antisera to rBCP, rBCP^∇IgA, III-rBCP, and III-rBCP^∇IgA opsonized GBS strains A909 (Ia/BCP⁺) and H36B (Ib/BCP⁺) for killing by HL-60 cells; antiserum to III-rBCP and III-rBCP^∇IgA also opsonized strain M781 (III/BCP^-). Vaccination of female mice with either rBCP or rBCP^∇IgA protected ∼40% of their pups challenged with GBS strain A909. Pups born to III-rBCP- or III-rBCP^∇IgA-vaccinated dams survived at rates of 56% and 66%, respectively. Over 90% of pups born to dams that received the type III CPS conjugates survived challenge with GBS strain M781. In summary, rBCP and rBCP^∇IgA proteins and the conjugates containing them were immunogenic in mice, inducing both CPS- and protein-specific functional IgG. These results suggest that the rBCP^∇IgA could be used as a carrier to augment the immunogenicity of the CPS while expanding coverage to GBS strains bearing BCP.

Revue / Journal Title

Infection and immunity    ISSN  0019-9567   CODEN INFIBR 

Source / Source

2007, vol. 75, n^o7, pp. 3455-3461 [7 page(s) (article)] (37 ref.)

Langue / Language

Anglais

Editeur / Publisher

American Society for Microbiology, Washington, DC, ETATS-UNIS  (1970) (Revue)

Mots-clés anglais / English Keywords

Vertebrata

;

Mammalia

;

Rodentia

;

Bacteria

;

Micrococcales

;

Streptococcaceae

;

Vaccine

;

Binding site

;

IgA

;

Mutation

;

Deletion

;

Protein

;

Mouse

;

Streptococcus B

;

Mots-clés français / French Keywords

Vertebrata

;

Mammalia

;

Rodentia

;

Bactérie

;

Micrococcales

;

Streptococcaceae

;

Vaccin

;

Site fixation

;

IgA

;

Mutation

;

Délétion

;

Protéine

;

Souris

;

Streptococcus B

;

Mots-clés espagnols / Spanish Keywords

Vertebrata

;

Mammalia

;

Rodentia

;

Bacteria

;

Micrococcales

;

Streptococcaceae

;

Vacuna

;

Sitio fijación

;

IgA

;

Mutación

;

Deleción

;

Proteína

;

Ratón

;

Streptococcus B

;

Localisation / Location

INIST-CNRS, Cote INIST : 15757, 35400016296577.0250