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

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Kunthalert, Duangkamol
Novotny, Laura A
Massa, Helen M
Ulett, Glen C
Bakaletz, Lauren O
Kyd, Jennelle M
Cripps, Allan W
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2013
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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.

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Human Vaccines & Immunotherapeutics
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9
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3
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© The Author(s) 2013. This is the author-manuscript version of this paper. It is posted here with permission of the copyright owners for your personal use only. No further distribution permitted. For information about this journal please refer to the journal’s website or contact the authors.
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Immunology
Immunology not elsewhere classified
Medical microbiology
Pharmacology and pharmaceutical sciences
Medical biotechnology
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