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Vaccine. 2014 Jan 9;32(3):375-82. doi: 10.1016/j.vaccine.2013.11.023. Epub 2013 Nov 16.

Alterations in immunodominance of Streptococcus mutans AgI/II: lessons learned from immunomodulatory antibodies.

Author information

1
Department of Oral Biology, University of Florida College of Dentistry, Gainesville, FL 32610, United States.
2
Department of Oral Biology, University of Florida College of Dentistry, Gainesville, FL 32610, United States. Electronic address: jbrady@dental.ufl.edu.

Abstract

Streptococcus mutans antigen I/II (AgI/II) has been widely studied as a candidate vaccine antigen against human dental caries. In this report we follow up on prior studies that indicated that anti-AgI/II immunomodulatory monoclonal antibodies (MAbs) exerted their effects by destabilizing the native protein structure and exposing cryptic epitopes. We show here that similar results can be obtained by immunizing mice with truncated polypeptides out of the context of an intra-molecular interaction that occurs within the full-length molecule and that appears to dampen the functional response against at least two important target epitopes. Putative T cell epitopes that influenced antibody specificity were identified immediately upstream of the alanine-rich repeat domain. Adherence inhibiting antibodies could be induced against two discrete domains of the protein, one corresponding to the central portion of the molecule and the other corresponding to the C-terminus.

KEYWORDS:

Immune complex; Immunodominance; Monoclonal antibody; Streptococcus; Vaccine design

PMID:
24252705
PMCID:
PMC3901311
DOI:
10.1016/j.vaccine.2013.11.023
[Indexed for MEDLINE]
Free PMC Article

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