Protection against Group A Streptococcus by Immunization with J8-Diphtheria Toxoid: Contribution of J8- and Diphtheria Toxoid-Specific Antibodies to Protection

A conformationally constrained, minimally conserved peptide from the M protein of group A streptococcus (GAS) has been defined. It consists of 12 amino acids from the C-repeat region within a non-M protein helix-forming sequence and is referred to as “J8.” Here, we investigate the immunogenicity of...

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Bibliographic Details
Published in:The Journal of infectious diseases 2003-05, Vol.187 (10), p.1598-1608
Main Authors: Batzloff, Michael R, Hayman, Wendy A, Davies, Mark R, Zeng, Ming, Pruksakorn, Sumalee, Brandt, Evelyn R, Good, Michael F
Format: Article
Language:English
Subjects:
Adjuvants, Immunologic
Alum Compounds - pharmacology
Animals
Antibodies, Bacterial - immunology
Bacteriology
Biological and medical sciences
Diphtheria Toxoid - immunology
Female
Fluorescent Antibody Technique
Fundamental and applied biological sciences. Psychology
Humans
Immunoglobulin G - immunology
Lipid A - analogs & derivatives
Lipid A - immunology
Male
Mice
Microbiology
Saponins - immunology
Streptococcal Infections - immunology
Streptococcal Infections - prevention & control
Streptococcus - immunology
Survival Rate
T-Lymphocytes - immunology
Time Factors
Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies
Vaccines, Conjugate - immunology
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Summary:A conformationally constrained, minimally conserved peptide from the M protein of group A streptococcus (GAS) has been defined. It consists of 12 amino acids from the C-repeat region within a non-M protein helix-forming sequence and is referred to as “J8.” Here, we investigate the immunogenicity of a J8-diphtheria toxoid (DT) conjugate adjuvanted with the human-compatible adjuvants, SBAS2 and alum, and demonstrate that it is capable of inducing opsonic antibodies and can protect outbred mice from virulent challenge. In a range of experiments, protection correlated with the titer of J8-specific antibodies and not with the induction of J8-specific T cells. However, DT-specific antibodies (as well as J8-specific antibodies) were shown to stain the surface of fixed GAS and to be capable of opsonizing live organisms. DT may be an ideal carrier protein for J8 and other GAS peptides for GAS vaccines
ISSN:0022-1899
1537-6613
DOI:10.1086/374800