Towards an Epitope-Based Human Vaccine for Influenza

Ben-Yedidia, Tamar; Arnon, Ruth

doi:10.4161/hv.1.3.1851

Cited by 38 publications

(20 citation statements)

References 71 publications

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“…For example, the flagellin protein of Salmonella can be used as a carrier protein linked to multiple copies of any foreign epitope. However, this approach was used for presentation of small peptides (4,5). Here we present data that support our hypothesis that one bacterial OMP can act as a carrier for a different OMP by providing multiple T-cell epitopes and expanding the repertoire of T-cell epitope presentation on the MHC class II molecules.…”

Section: Vol 76 2008supporting

confidence: 74%

Physical Linkage of Naturally Complexed Bacterial Outer Membrane Proteins Enhances Immunogenicity

et al. 2008

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The outer membrane proteins (OMPs) of bacterial pathogens are essential for their growth and survival and especially for attachment and invasion of host cells. Since the outer membrane is the interface between the bacterium and the host cell, outer membranes and individual OMPs are targeted for development of vaccines against many bacterial diseases. Whole outer membrane fractions often protect against disease, and this protection cannot be fully reproduced by using individual OMPs. Exactly how the interactions among individual OMPs influence immunity is not well understood. We hypothesized that one OMP rich in T-cell epitopes can act as a carrier for an associated OMP which is poor in T-cell epitopes to generate T-dependent antibody responses, similar to the hapten-carrier effect. Outer membrane proteins (OMPs) mediate interactions between microbial pathogens and their hosts. Within the bacterial outer membrane, proteins exist in homomeric or heteromeric complexes that are dependent on covalent as well as noncovalent interactions. These complexes are essential structural components and also mediate central events in bacterial physiology and pathogenesis. For example, the extensive disulfide cross-linking of chlamydial major outer membrane proteins (MOMPs) (15,22,40) provides structural stability in the absence of peptidoglycan (14), and disulfide interactions among MOMPs regulate porin function (3). The Escherichia coli outer membrane contains a complex consisting of a large ␤-barrel protein, Imp, and a small lipoprotein, RlpB, and both proteins are required for lipopolysaccharide assembly (39). Furthermore, protein complexes within the membrane, including sophisticated macromolecular structures, such as secretion systems and pili, are essential for attachment, invasion, and survival within host cells (33).How OMP interactions affect induction of immunity is poorly understood. Numerous vaccine studies have been directed at individual OMPs, but these OMPs had limited success compared to immunization using whole bacteria or intact outer membranes. For example, immunization with outer membranes from Chlamydia trachomatis, Francisella tularensis, Haemophilus influenzae, and Anaplasma marginale protects against bacterial challenge, whereas immunization with MOMPs from these bacteria does not protect against bacterial challenge (1, 8, 10-12, 16, 26, 29, 36). The immunologic importance of OMP complexes is demonstrated by the induction of protection against Leptospira by immunization using OmpL1 and LipL41 expressed simultaneously in the context of the E. coli membrane. In contrast, immunization with either protein alone in the membrane context or as part of a mixture of non-membrane-associated proteins is not protective (13). Understanding the basis for differences in the immunogenicity and efficacy of complexed OMPs and individual OMPs would enhance design and development of vaccines for multiple bacterial pathogens.We have hypothesized that bacterial OMPs act as a carrierhapten pair, with one OMP containing essentia...

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Section: Vol 76 2008supporting

confidence: 74%

Physical Linkage of Naturally Complexed Bacterial Outer Membrane Proteins Enhances Immunogenicity

et al. 2008

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“…Thus, epitopes may be classified as T- or B-cell epitopes (13,14). With the development of bioinformatic technology, epitope vaccines (15) have become increasingly important in immune prevention. Superior to traditional vaccines, vaccines based on epitopes are currently used as protective measures against infectious diseases.…”

Section: Introductionmentioning

confidence: 99%

Bioinformatic prediction of epitopes in the Emy162 antigen of Echinococcus multilocularis

Lǐ

Liu

Zhu

et al. 2013

Experimental and Therapeutic Medicine

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The aim of the present study was to predict the secondary structure and the T- and B-cell epitopes of the Echinococcus multilocularis Emy162 antigen, in order to reveal the dominant epitopes of the antigen. The secondary structure of the protein was analyzed using the Gamier-Robson method, and the improved self-optimized prediction method (SOPMA) server. The T- and B-cell epitopes of Emy162 were predicted using Immune Epitope Database (IEDB), Syfpeithi, Bcepred and ABCpred online software. The characteristics of hydrophilicity, flexibility, antigenic propensity and exposed surface area were predicted. The tertiary structure of the Emy162 protein was predicted by the 3DLigandSite server. The results demonstrated that random coils and β sheets accounted for 34.64 and 21.57% of the secondary structure of the Emy162 protein, respectively. This was indicative of the presence of potential dominant antigenic epitopes in Emy162. Following bioinformatic analysis, numerous distinct antigenic epitopes of Emy162 were identified. The high-scoring T-cell epitopes were located at positions 16–29, 36–39, 97–103, 119–125 and 128–135, whilst the likely B-cell epitopes were located at positions 8–10, 19–25, 44–50, 74–81, 87–93, 104–109 and 128–136. In conclusion, five T-cell and seven B-cell dominant epitopes of the Emy162 antigen were revealed by the bioinformatic methods, which may be of use in the development of a dominant epitope vaccine.

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“…[2][3][4] Transgenic bacteria expressing modified flagella incorporating antigens have been described as suitable antigen carriers and adjuvants for the development of vaccines for infectious diseases. 5,6 Ben-Yedidia and Arnon 7 suggested the usage of the TLR5 ligand flagellin, the main constituent of bacterial flagella, to strengthen specific immune responses against foreign antigens. Flagellin activates TLR5-expressing cells, potentially leading to an enhanced immune response to foreign epitopes, and improves immune responses after local mucosal application.…”

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confidence: 99%

“…Flagellin activates TLR5-expressing cells, potentially leading to an enhanced immune response to foreign epitopes, and improves immune responses after local mucosal application. 5 Consequently, flagellin has gained attention as an adjuvant for the prevention of type I allergy. In a murine model of OVA-induced airway hyperreactivity, intranasal coadministration of flagellin mixed with ovalbumin (OVA) resulted in the suppression of airway hyperreactivity, inflammation, and OVA-specific T H 2 cytokine secretion.…”

mentioning

confidence: 99%

A fusion protein of flagellin and ovalbumin suppresses the TH2 response and prevents murine intestinal allergy

Schülke

Burggraf

Waibler

et al. 2011

Journal of Allergy and Clinical Immunology

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Towards an Epitope-Based Human Vaccine for Influenza

Cited by 38 publications

References 71 publications

Physical Linkage of Naturally Complexed Bacterial Outer Membrane Proteins Enhances Immunogenicity

Physical Linkage of Naturally Complexed Bacterial Outer Membrane Proteins Enhances Immunogenicity

Bioinformatic prediction of epitopes in the Emy162 antigen of Echinococcus multilocularis

A fusion protein of flagellin and ovalbumin suppresses the TH2 response and prevents murine intestinal allergy

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