Epitope-specific immune recognition of the nontypeable Haemophilus influenzae outer membrane protein 26.
Hum Vaccin Immunother
; 9(3): 625-35, 2013 Mar.
Article
in En
| MEDLINE
| ID: mdl-23292125
ABSTRACT
Previous studies using rodent respiratory infection models of nontypeable Haemophilus influenzae (NTHi) infection have established the 26-kDa outer membrane protein of the bacterium, OMP26, as a potential vaccine antigen for NTHi. This study undertook a comprehensive immunological identification of OMP26 T- and B-cell epitopes. A series of OMP26 peptides were constructed and regions of the OMP26 antigen involved in recognition by lymphocyte receptors and induction of acquired immune responses were identified. The dominant T-cell epitopes for OMP26 were located toward the C-terminus between amino acid residues 95 and 197 (T3+T4 region) as mapped using antigen-specific lymphocyte proliferation assays. The newly identified T-cell epitopes exhibited strong capacity for efficient T-cell activation, suggesting that, compared with other OMP26 regions; epitopes within the T3+T4 region have the highest affinity for binding to major histocompatibility complex molecules. In contrast, the predominant B-cell epitopes of OMP26 were located more centrally within the molecule between amino acid residues 45 and 145 (T2+T3 region) as determined using enzyme-linked immunosorbent assay and surface plasmon resonance assays. The T2+T3 region was immunodominant in several species including chinchilla, mice and rats when assessed using both mucosal and parenteral immunization regimes. In addition, the antibodies directed against the T2+T3 region bound to intact NTHi cell surface, according to flow cytometry. Collectively, these results specifically locate the amino acid sequences containing the OMP26 T- and B-cell epitopes, which, as newly mapped antigenic epitopes for lymphocyte recognition, will be useful to improve existing NTHi vaccine strategies. Comprehensive definition of the minimum epitope length required for optimal B- and T-cell responses requires further study.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Bacterial Outer Membrane Proteins
/
Haemophilus influenzae
/
Epitope Mapping
/
Epitopes, T-Lymphocyte
/
Epitopes, B-Lymphocyte
Limits:
Animals
Language:
En
Journal:
Hum Vaccin Immunother
Year:
2013
Document type:
Article
Affiliation country:
Thailand