Immunogenicity and protective efficacy of the alpha C protein of group B streptococci are inversely related to the number of repeats

Claudia Gravekamp, Dennis L. Kasper, James L. Michel, David E. Kling, Vincent Carey, Lawrence C. Madoff

Research output: Contribution to journalArticle

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Abstract

Infection by group B streptococci (GBS) is an important cause of bacterial disease in neonates. Alpha C protein is a protective cell surface- associated protein of GBS. This protein contains a repeat region flanked by N and C termini. Variable expression of tandem repeating units of alpha C proteins had been found among clinical isolates of GBS. We examined the effect of the number of repeats on the immunogenicity of the alpha C protein and its ability to elicit protection from GBS infection in a neonatal mouse model. Mice were immunized with purified alpha C proteins of constructs containing various numbers of repeats (n = 1, 2, 9, and 16) and the N- and C- terminal regions. Both the N-terminal and the repeat regions contain protective and opsonic epitopes. Antibody responses to the alpha C protein constructs with various numbers of repeats were tested with enzyme-linked immunosorbent assay plates coated with either native, nine-repeat alpha C protein or 'repeatless' N-terminal antigen. An inverse relationship was found between the number of repeats and the immunogenicity of the alpha C protein; this effect was most pronounced on titers of antibody to the N-terminal region. An inverse relationship was also observed between the number of repeats and protective efficacy, i.e., mouse dams immunized with 5 μg of one- or nine-repeat alpha C protein transferred protective immunity to 65 or 11% of their pups, respectively (P < 0.0001). Thus, the presence of multiple repeats appears to lessen the antibody response to the complete alpha C protein, and especially the antibody response to its N-terminal region, and suggests a mechanism whereby repeat elements contribute to the evasion of host immunity.

Original languageEnglish (US)
Pages (from-to)5216-5221
Number of pages6
JournalInfection and Immunity
Volume65
Issue number12
StatePublished - 1997
Externally publishedYes

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Protein C
Streptococcus agalactiae
Antibody Formation
Immunity
group B streptococci alpha C protein
Terminal Repeat Sequences
Infection
Streptococcus
Epitopes
Membrane Proteins
Enzyme-Linked Immunosorbent Assay
Antigens
Antibodies

ASJC Scopus subject areas

  • Immunology

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Immunogenicity and protective efficacy of the alpha C protein of group B streptococci are inversely related to the number of repeats. / Gravekamp, Claudia; Kasper, Dennis L.; Michel, James L.; Kling, David E.; Carey, Vincent; Madoff, Lawrence C.

In: Infection and Immunity, Vol. 65, No. 12, 1997, p. 5216-5221.

Research output: Contribution to journalArticle

Gravekamp, Claudia ; Kasper, Dennis L. ; Michel, James L. ; Kling, David E. ; Carey, Vincent ; Madoff, Lawrence C. / Immunogenicity and protective efficacy of the alpha C protein of group B streptococci are inversely related to the number of repeats. In: Infection and Immunity. 1997 ; Vol. 65, No. 12. pp. 5216-5221.
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abstract = "Infection by group B streptococci (GBS) is an important cause of bacterial disease in neonates. Alpha C protein is a protective cell surface- associated protein of GBS. This protein contains a repeat region flanked by N and C termini. Variable expression of tandem repeating units of alpha C proteins had been found among clinical isolates of GBS. We examined the effect of the number of repeats on the immunogenicity of the alpha C protein and its ability to elicit protection from GBS infection in a neonatal mouse model. Mice were immunized with purified alpha C proteins of constructs containing various numbers of repeats (n = 1, 2, 9, and 16) and the N- and C- terminal regions. Both the N-terminal and the repeat regions contain protective and opsonic epitopes. Antibody responses to the alpha C protein constructs with various numbers of repeats were tested with enzyme-linked immunosorbent assay plates coated with either native, nine-repeat alpha C protein or 'repeatless' N-terminal antigen. An inverse relationship was found between the number of repeats and the immunogenicity of the alpha C protein; this effect was most pronounced on titers of antibody to the N-terminal region. An inverse relationship was also observed between the number of repeats and protective efficacy, i.e., mouse dams immunized with 5 μg of one- or nine-repeat alpha C protein transferred protective immunity to 65 or 11{\%} of their pups, respectively (P < 0.0001). Thus, the presence of multiple repeats appears to lessen the antibody response to the complete alpha C protein, and especially the antibody response to its N-terminal region, and suggests a mechanism whereby repeat elements contribute to the evasion of host immunity.",
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