Peptide mimotopes as surrogate antigens of carbohydrates in vaccine discovery

Monzavi‐Karbassi, Behjatolah; Cunto-Amesty, Gina; Luo, Ping; Kieber‐Emmons, Thomas

doi:10.1016/s0167-7799(02)01940-6

Cited by 76 publications

(57 citation statements)

References 62 publications

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“…Because oligomannosidic glycans from natural sources are only available in limited amounts and also difficult to synthesize chemically, we had to use a surrogate to achieve our goal. Peptides have shown to structurally and functionally mimic oligosaccharides (Pirofski, 2001;Johnson et al, 2002;Monzavi-Karbassi et al, 2002) and thus are potential surrogates for carbohydrates. Therefore, we first attempted to isolate an oligomannose-mimicking peptide.…”

Section: Identification Of An Oligomannose-mimicking Peptidementioning

confidence: 99%

Synapsin I Is an Oligomannose-Carrying Glycoprotein, Acts As an Oligomannose-Binding Lectin, and Promotes Neurite Outgrowth and Neuronal Survival When Released via Glia-Derived Exosomes

Wang¹,

Cesca²,

Loers³

et al. 2011

J. Neurosci.

276

201

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Section: Identification Of An Oligomannose-mimicking Peptidementioning

confidence: 99%

Synapsin I Is an Oligomannose-Carrying Glycoprotein, Acts As an Oligomannose-Binding Lectin, and Promotes Neurite Outgrowth and Neuronal Survival When Released via Glia-Derived Exosomes

Wang¹,

Cesca²,

Loers³

et al. 2011

J. Neurosci.

276

201

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“…Their binding affinities are often similar to or greater than those of the native ligands, and consensus sequences for groups of crossreactive peptides have been identified (5,6). These peptides are lead candidates for vaccine development (7,8). When used as immunogens, they may elicit carbohydrate-binding antibody responses (7,8).…”

mentioning

confidence: 99%

“…These peptides are lead candidates for vaccine development (7,8). When used as immunogens, they may elicit carbohydrate-binding antibody responses (7,8). The design of an effective vaccine that elicits an antipolysaccharide response, based on a peptide mimetic that is complementary to only one monoclonal Ab, has precedent in the case of a vaccine against Group B Streptococcus polysaccharide, based on carbohydrate-mimetic peptides (9).…”

mentioning

confidence: 99%

“…Whether either structural or functional mimicry is a prerequisite for mimetic peptides to elicit carbohydrate-binding antibodies, and thus for vaccine development (5,7,8), is a further question that remains to be probed. As a first step in this program, we present structural evidence that shows that the mechanism of peptide binding differs from that of carbohydrate in the binding to an antibody.…”

mentioning

confidence: 99%

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Structural basis of peptide–carbohydrate mimicry in an antibody-combining site

Vyas

Chervenak

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

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“…Indeed, because of their ease of production and their intrinsic immunogenic properties, peptide mimotopes may have several advantages over incorporating complex carbohydrate haptens issued from bacterial cell cultures or low yielding syntheses. Phage display libraries are commonly used to identify peptide mimics of various surface carbohydrate structures of pathogenic bacteria (26). A phage display library in which random peptides are expressed on the surface of filamentous phage provides a source of structurally diverse mimics (27).…”

mentioning

confidence: 99%

Development of Peptide Mimics of a Protective Epitope of Vibrio cholerae Ogawa O-antigen and Investigation of the Structural Basis of Peptide Mimicry

Dharmasena

Jewell

Taylor

2007

Journal of Biological Chemistry

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As an alternative approach toward the development of a cholera vaccine, the potential of peptide mimics of Vibrio cholerae lipopolysaccharide (LPS) to elicit cross-reactive immune responses against LPS was investigated. Two closely related protective monoclonal antibodies, S-20-4 and A-20-6, which are specific for Ogawa O-antigen (O-specific polysaccharide; O-SP) of V. cholerae O1, were used as the target antibodies (Abs) to pan phage display libraries under different elution conditions. Six phage clones identified from S-20-4 panning showed significant binding to both S-20-4 and A-20-6. Thus, it is likely that these phage-displayed peptides mimic an important conformational epitope of Ogawa antigens and are not simply functionally recognized by S-20-4. Each of the six phage clones that could bind to both monoclonal antibodies also competed with LPS for binding to S-20-4, suggesting that the peptides bind close to the paratope of the Ab. In order to predict how these peptide mimics interact with S-20-4 compared with its carbohydrate counterpart, one peptide mimic, 4P-8, which is one of the highest affinity binders and shares motifs with several other peptide mimics, was selected for further studies using computer modeling methods and site-directed mutagenesis. These studies suggest that 4P-8 is recognized as a hairpin structure that mimics some O-SP interactions with S-20-4 and also makes unique ligand interactions with S-20-4. In addition, 4P-8-KLH was able to elicit anti-LPS Abs in mice, but the immune response was not vibriocidal or protective. However, boosting with 4P-8-KLH after immunizing with LPS prolonged the LPS-reactive IgG and IgM Ab responses as well as vibriocidal titers and provided a much greater degree of protection than priming with LPS alone.Cholera is a severe diarrheal disease caused by the bacterium Vibrio cholerae, which is prevalent in many developing countries. According to the World Health Organization, an estimated 120,000 deaths occur from cholera worldwide each year. Although the establishment of clean water and food, adequate personal hygiene, and sanitation are the long term solutions for cholera control, in the short term, sufficient improvements in these areas are difficult to achieve in most cholera-endemic areas. Meanwhile, there is an urgent need for improved vaccines as an additional public health tool for cholera prevention (1). Since the affected population is very poor, development of an inexpensive vaccine is most desirable.Currently available vaccines for cholera are based on killed, whole cell, or live attenuated formulations. The killed, whole cell (WC and WCrBS) vaccines provide only partial short term protection. The live, attenuated strains, such as CVD 103-HgR, have greatly improved efficacy in North American volunteers but have not been proven efficacious in field trials (1, 2). However, field trials of the live attenuated strain Peru-15 have proven to be safe, immunogenic, and efficacious (3). An approach that could serve as an alternative or be used to augment e...

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Peptide mimotopes as surrogate antigens of carbohydrates in vaccine discovery

Cited by 76 publications

References 62 publications

Synapsin I Is an Oligomannose-Carrying Glycoprotein, Acts As an Oligomannose-Binding Lectin, and Promotes Neurite Outgrowth and Neuronal Survival When Released via Glia-Derived Exosomes

Synapsin I Is an Oligomannose-Carrying Glycoprotein, Acts As an Oligomannose-Binding Lectin, and Promotes Neurite Outgrowth and Neuronal Survival When Released via Glia-Derived Exosomes

Structural basis of peptide–carbohydrate mimicry in an antibody-combining site

Development of Peptide Mimics of a Protective Epitope of Vibrio cholerae Ogawa O-antigen and Investigation of the Structural Basis of Peptide Mimicry

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