Epitope-specific immune recognition of the nontypeable Haemophilus influenzae outer membrane protein 26.

Hum Vaccin Immunother. 2013 Jan 4;9(3).

Kunthalert D, Novotny LA, Massa HM, Ulett GC, Bakaletz LO, Kyd JM, Cripps AW.

Faculty of Medical Science; Naresuan University; Phitsanulok, Thailand.

 

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.

KEYWORDS:

B and T-cell epitopes, OMP26, immune response, mucosal, nontypeable Haemophilus influenzae, outer membrane protein, parenteral, peptide vaccine, vaccine

PMID: 23292125

 

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