Pentamers Not Found in the Universal Proteome Can Enhance Antigen Specific Immune Responses and Adjuvant Vaccines
Identifieur interne : 001289 ( Pmc/Checkpoint ); précédent : 001288; suivant : 001290Pentamers Not Found in the Universal Proteome Can Enhance Antigen Specific Immune Responses and Adjuvant Vaccines
Auteurs : Ami Patel [Canada] ; Jessica C. Dong [Canada] ; Brett Trost [Canada] ; Jason S. Richardson [Canada] ; Sarah Tohme [Canada] ; Shawn Babiuk [Canada] ; Anthony Kusalik [Canada] ; Sam K. P. Kung [Canada] ; Gary P. Kobinger [Canada]Source :
- PLoS ONE [ 1932-6203 ] ; 2012.
Abstract
Certain short peptides do not occur in humans and are rare or non-existent in the universal proteome. Antigens that contain rare amino acid sequences are in general highly immunogenic and may activate different arms of the immune system. We first generated a list of rare, semi-common, and common 5-mer peptides using bioinformatics tools to analyze the UniProtKB database. Experimental observations indicated that rare and semi-common 5-mers generated stronger cellular responses in comparison with common-occurring sequences. We hypothesized that the biological process responsible for this enhanced immunogenicity could be used to positively modulate immune responses with potential application for vaccine development. Initially, twelve rare 5-mers, 9-mers, and 13-mers were incorporated in frame at the end of an H5N1 hemagglutinin (HA) antigen and expressed from a DNA vaccine. The presence of some 5-mer peptides induced improved immune responses. Adding one 5-mer peptide exogenously also offered improved clinical outcome and/or survival against a lethal H5N1 or H1N1 influenza virus challenge in BALB/c mice and ferrets, respectively. Interestingly, enhanced anti-HBsAg antibody production by up to 25-fold in combination with a commercial Hepatitis B vaccine (Engerix-B, GSK) was also observed in BALB/c mice. Mechanistically, NK cell activation and dependency was observed with enhancing peptides ex vivo and in NK-depleted mice. Overall, the data suggest that rare or non-existent oligopeptides can be developed as immunomodulators and supports the further evaluation of some 5-mer peptides as potential vaccine adjuvants.
Url:
DOI: 10.1371/journal.pone.0043802
PubMed: 22937099
PubMed Central: 3427150
Affiliations:
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Dong</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg</wicri:regionArea><wicri:noRegion>Winnipeg</wicri:noRegion></affiliation><affiliation wicri:level="4"><nlm:aff id="aff3"><addr-line>Department of Immunology, University of Manitoba, Winnipeg, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Immunology, University of Manitoba, Winnipeg</wicri:regionArea><orgName type="university">Université du Manitoba</orgName><placeName><settlement type="city">Winnipeg</settlement><region type="state">Manitoba</region></placeName></affiliation></author><author><name sortKey="Trost, Brett" sort="Trost, Brett" uniqKey="Trost B" first="Brett" last="Trost">Brett Trost</name><affiliation wicri:level="1"><nlm:aff id="aff4"><addr-line>Department of Computer Science, University of Saskatchewan, Saskatoon, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Computer Science, University of Saskatchewan, Saskatoon</wicri:regionArea><wicri:noRegion>Saskatoon</wicri:noRegion></affiliation></author><author><name sortKey="Richardson, Jason S" sort="Richardson, Jason S" uniqKey="Richardson J" first="Jason S." last="Richardson">Jason S. Richardson</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg</wicri:regionArea><wicri:noRegion>Winnipeg</wicri:noRegion></affiliation></author><author><name sortKey="Tohme, Sarah" sort="Tohme, Sarah" uniqKey="Tohme S" first="Sarah" last="Tohme">Sarah Tohme</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg</wicri:regionArea><wicri:noRegion>Winnipeg</wicri:noRegion></affiliation></author><author><name sortKey="Babiuk, Shawn" sort="Babiuk, Shawn" uniqKey="Babiuk S" first="Shawn" last="Babiuk">Shawn Babiuk</name><affiliation wicri:level="4"><nlm:aff id="aff3"><addr-line>Department of Immunology, University of Manitoba, Winnipeg, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Immunology, University of Manitoba, Winnipeg</wicri:regionArea><orgName type="university">Université du Manitoba</orgName><placeName><settlement type="city">Winnipeg</settlement><region type="state">Manitoba</region></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="aff5"><addr-line>National Centre for Foreign Animal Disease, Canadian Food Inspection Agency, Winnipeg, Manitoba, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>National Centre for Foreign Animal Disease, Canadian Food Inspection Agency, Winnipeg, Manitoba</wicri:regionArea><wicri:noRegion>Manitoba</wicri:noRegion></affiliation></author><author><name sortKey="Kusalik, Anthony" sort="Kusalik, Anthony" uniqKey="Kusalik A" first="Anthony" last="Kusalik">Anthony Kusalik</name><affiliation wicri:level="1"><nlm:aff id="aff4"><addr-line>Department of Computer Science, University of Saskatchewan, Saskatoon, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Computer Science, University of Saskatchewan, Saskatoon</wicri:regionArea><wicri:noRegion>Saskatoon</wicri:noRegion></affiliation></author><author><name sortKey="Kung, Sam K P" sort="Kung, Sam K P" uniqKey="Kung S" first="Sam K. P." last="Kung">Sam K. P. Kung</name><affiliation wicri:level="4"><nlm:aff id="aff3"><addr-line>Department of Immunology, University of Manitoba, Winnipeg, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Immunology, University of Manitoba, Winnipeg</wicri:regionArea><orgName type="university">Université du Manitoba</orgName><placeName><settlement type="city">Winnipeg</settlement><region type="state">Manitoba</region></placeName></affiliation></author><author><name sortKey="Kobinger, Gary P" sort="Kobinger, Gary P" uniqKey="Kobinger G" first="Gary P." last="Kobinger">Gary P. Kobinger</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg</wicri:regionArea><wicri:noRegion>Winnipeg</wicri:noRegion></affiliation><affiliation wicri:level="4"><nlm:aff id="aff2"><addr-line>Department of Medical Microbiology, University of Manitoba, Winnipeg, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Medical Microbiology, University of Manitoba, Winnipeg</wicri:regionArea><orgName type="university">Université du Manitoba</orgName><placeName><settlement type="city">Winnipeg</settlement><region type="state">Manitoba</region></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="aff3"><addr-line>Department of Immunology, University of Manitoba, Winnipeg, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Immunology, University of Manitoba, Winnipeg</wicri:regionArea><orgName type="university">Université du Manitoba</orgName><placeName><settlement type="city">Winnipeg</settlement><region type="state">Manitoba</region></placeName></affiliation></author></analytic><series><title level="j">PLoS ONE</title><idno type="eISSN">1932-6203</idno><imprint><date when="2012">2012</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Certain short peptides do not occur in humans and are rare or non-existent in the universal proteome. Antigens that contain rare amino acid sequences are in general highly immunogenic and may activate different arms of the immune system. We first generated a list of rare, semi-common, and common 5-mer peptides using bioinformatics tools to analyze the UniProtKB database. Experimental observations indicated that rare and semi-common 5-mers generated stronger cellular responses in comparison with common-occurring sequences. We hypothesized that the biological process responsible for this enhanced immunogenicity could be used to positively modulate immune responses with potential application for vaccine development. Initially, twelve rare 5-mers, 9-mers, and 13-mers were incorporated in frame at the end of an H5N1 hemagglutinin (HA) antigen and expressed from a DNA vaccine. The presence of some 5-mer peptides induced improved immune responses. Adding one 5-mer peptide exogenously also offered improved clinical outcome and/or survival against a lethal H5N1 or H1N1 influenza virus challenge in BALB/c mice and ferrets, respectively. Interestingly, enhanced anti-HBsAg antibody production by up to 25-fold in combination with a commercial Hepatitis B vaccine (Engerix-B, GSK) was also observed in BALB/c mice. Mechanistically, NK cell activation and dependency was observed with enhancing peptides ex vivo and in NK-depleted mice. Overall, the data suggest that rare or non-existent oligopeptides can be developed as immunomodulators and supports the further evaluation of some 5-mer peptides as potential vaccine adjuvants.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Kanduc, D" uniqKey="Kanduc D">D Kanduc</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kanduc, D" uniqKey="Kanduc D">D Kanduc</name></author><author><name sortKey="Tessitore, L" uniqKey="Tessitore L">L Tessitore</name></author><author><name sortKey="Lucchese, G" uniqKey="Lucchese G">G Lucchese</name></author><author><name sortKey="Kusalik, A" uniqKey="Kusalik A">A Kusalik</name></author><author><name sortKey="Farber, E" uniqKey="Farber E">E Farber</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lucchese, G" uniqKey="Lucchese G">G Lucchese</name></author><author><name sortKey="Stufano, A" uniqKey="Stufano A">A 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<front><journal-meta><journal-id journal-id-type="nlm-ta">PLoS One</journal-id><journal-id journal-id-type="iso-abbrev">PLoS ONE</journal-id><journal-id journal-id-type="publisher-id">plos</journal-id><journal-id journal-id-type="pmc">plosone</journal-id><journal-title-group><journal-title>PLoS ONE</journal-title></journal-title-group><issn pub-type="epub">1932-6203</issn><publisher><publisher-name>Public Library of Science</publisher-name><publisher-loc>San Francisco, USA</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">22937099</article-id><article-id pub-id-type="pmc">3427150</article-id><article-id pub-id-type="publisher-id">PONE-D-12-10753</article-id><article-id pub-id-type="doi">10.1371/journal.pone.0043802</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="Discipline-v2"><subject>Biology</subject><subj-group><subject>Immunology</subject><subj-group><subject>Immune cells</subject><subj-group><subject>NK cells</subject></subj-group></subj-group><subj-group><subject>Immunity</subject><subj-group><subject>Immunity to Infections</subject><subject>Innate Immunity</subject></subj-group></subj-group><subj-group><subject>Immunomodulation</subject></subj-group></subj-group><subj-group><subject>Microbiology</subject><subj-group><subject>Immunity</subject><subj-group><subject>Immune Activation</subject><subject>Immunotherapy</subject><subject>Innate Immunity</subject></subj-group></subj-group></subj-group><subj-group><subject>Proteomics</subject><subj-group><subject>Proteomic Databases</subject></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v2"><subject>Medicine</subject><subj-group><subject>Clinical Immunology</subject><subj-group><subject>Immunity</subject><subj-group><subject>Vaccination</subject><subj-group><subject>Vaccines</subject><subject>Vaccine Development</subject></subj-group></subj-group></subj-group></subj-group></subj-group></article-categories><title-group><article-title>Pentamers Not Found in the Universal Proteome Can Enhance Antigen Specific Immune Responses and Adjuvant Vaccines</article-title><alt-title alt-title-type="running-head">Rare Pentamers Can Adjuvant Vaccines</alt-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Patel</surname><given-names>Ami</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="aff" rid="aff2"><sup>2</sup></xref><xref ref-type="author-notes" rid="fn1"><sup>¤</sup></xref></contrib><contrib contrib-type="author"><name><surname>Dong</surname><given-names>Jessica C.</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="aff" rid="aff3"><sup>3</sup></xref></contrib><contrib contrib-type="author"><name><surname>Trost</surname><given-names>Brett</given-names></name><xref ref-type="aff" rid="aff4"><sup>4</sup></xref></contrib><contrib contrib-type="author"><name><surname>Richardson</surname><given-names>Jason S.</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Tohme</surname><given-names>Sarah</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Babiuk</surname><given-names>Shawn</given-names></name><xref ref-type="aff" rid="aff3"><sup>3</sup></xref><xref ref-type="aff" rid="aff5"><sup>5</sup></xref></contrib><contrib contrib-type="author"><name><surname>Kusalik</surname><given-names>Anthony</given-names></name><xref ref-type="aff" rid="aff4"><sup>4</sup></xref></contrib><contrib contrib-type="author"><name><surname>Kung</surname><given-names>Sam K. P.</given-names></name><xref ref-type="aff" rid="aff3"><sup>3</sup></xref></contrib><contrib contrib-type="author"><name><surname>Kobinger</surname><given-names>Gary P.</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="aff" rid="aff2"><sup>2</sup></xref><xref ref-type="aff" rid="aff3"><sup>3</sup></xref><xref ref-type="corresp" rid="cor1"><sup>*</sup></xref></contrib></contrib-group><aff id="aff1"><label>1</label><addr-line>Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Canada</addr-line></aff><aff id="aff2"><label>2</label><addr-line>Department of Medical Microbiology, University of Manitoba, Winnipeg, Canada</addr-line></aff><aff id="aff3"><label>3</label><addr-line>Department of Immunology, University of Manitoba, Winnipeg, Canada</addr-line></aff><aff id="aff4"><label>4</label><addr-line>Department of Computer Science, University of Saskatchewan, Saskatoon, Canada</addr-line></aff><aff id="aff5"><label>5</label><addr-line>National Centre for Foreign Animal Disease, Canadian Food Inspection Agency, Winnipeg, Manitoba, Canada</addr-line></aff><contrib-group><contrib contrib-type="editor"><name><surname>Marques</surname><given-names>Ernesto T.</given-names></name><role>Editor</role><xref ref-type="aff" rid="edit1"></xref></contrib></contrib-group><aff id="edit1"><addr-line>University of Pittsburgh, United States of America</addr-line></aff><author-notes><corresp id="cor1">* E-mail: <email>gary_kobinger@phac-aspc.gc.ca</email></corresp><fn fn-type="COI-statement"><p><bold>Competing Interests: </bold>The authors have declared that no competing interests exist.</p></fn><fn fn-type="con"><p>Conceived and designed the experiments: AP GK. Performed the experiments: AP JCD BT JSR ST GK. Analyzed the data: AP JCD BT AK SKPK GK. Contributed reagents/materials/analysis tools: SB AK SKPK. Wrote the paper: AP GK.</p></fn><fn id="fn1" fn-type="current-aff"><label>¤</label><p>Current address: San Raffaele Telethon Institute for Gene Therapy, Milan, Italy</p></fn></author-notes><pub-date pub-type="collection"><year>2012</year></pub-date><pub-date pub-type="epub"><day>24</day><month>8</month><year>2012</year></pub-date><volume>7</volume><issue>8</issue><elocation-id>e43802</elocation-id><history><date date-type="received"><day>16</day><month>4</month><year>2012</year></date><date date-type="accepted"><day>26</day><month>7</month><year>2012</year></date></history><permissions><copyright-statement>© 2012 Patel et al</copyright-statement><copyright-year>2012</copyright-year><copyright-holder>Patel et al</copyright-holder><license xlink:href="http://creativecommons.org/licenses/by/4.0/"><license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.</license-p></license></permissions><abstract><p>Certain short peptides do not occur in humans and are rare or non-existent in the universal proteome. Antigens that contain rare amino acid sequences are in general highly immunogenic and may activate different arms of the immune system. We first generated a list of rare, semi-common, and common 5-mer peptides using bioinformatics tools to analyze the UniProtKB database. Experimental observations indicated that rare and semi-common 5-mers generated stronger cellular responses in comparison with common-occurring sequences. We hypothesized that the biological process responsible for this enhanced immunogenicity could be used to positively modulate immune responses with potential application for vaccine development. Initially, twelve rare 5-mers, 9-mers, and 13-mers were incorporated in frame at the end of an H5N1 hemagglutinin (HA) antigen and expressed from a DNA vaccine. The presence of some 5-mer peptides induced improved immune responses. Adding one 5-mer peptide exogenously also offered improved clinical outcome and/or survival against a lethal H5N1 or H1N1 influenza virus challenge in BALB/c mice and ferrets, respectively. Interestingly, enhanced anti-HBsAg antibody production by up to 25-fold in combination with a commercial Hepatitis B vaccine (Engerix-B, GSK) was also observed in BALB/c mice. Mechanistically, NK cell activation and dependency was observed with enhancing peptides ex vivo and in NK-depleted mice. Overall, the data suggest that rare or non-existent oligopeptides can be developed as immunomodulators and supports the further evaluation of some 5-mer peptides as potential vaccine adjuvants.</p></abstract><funding-group><funding-statement>The research in this manuscript was supported by the Public Health Agency of Canada grant #531252 and a grant from the Canadian Institutes of Health Research. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.</funding-statement></funding-group><counts><page-count count="13"></page-count></counts></article-meta></front></pmc><affiliations><list><country><li>Canada</li></country><region><li>Manitoba</li></region><settlement><li>Winnipeg</li></settlement><orgName><li>Université du Manitoba</li></orgName></list><tree><country name="Canada"><noRegion><name sortKey="Patel, Ami" sort="Patel, Ami" uniqKey="Patel A" first="Ami" last="Patel">Ami Patel</name></noRegion><name sortKey="Babiuk, Shawn" sort="Babiuk, Shawn" uniqKey="Babiuk S" first="Shawn" last="Babiuk">Shawn Babiuk</name><name sortKey="Babiuk, Shawn" sort="Babiuk, Shawn" uniqKey="Babiuk S" first="Shawn" last="Babiuk">Shawn Babiuk</name><name sortKey="Dong, Jessica C" sort="Dong, Jessica C" uniqKey="Dong J" first="Jessica C." last="Dong">Jessica C. Dong</name><name sortKey="Dong, Jessica C" sort="Dong, Jessica C" uniqKey="Dong J" first="Jessica C." last="Dong">Jessica C. Dong</name><name sortKey="Kobinger, Gary P" sort="Kobinger, Gary P" uniqKey="Kobinger G" first="Gary P." last="Kobinger">Gary P. Kobinger</name><name sortKey="Kobinger, Gary P" sort="Kobinger, Gary P" uniqKey="Kobinger G" first="Gary P." last="Kobinger">Gary P. Kobinger</name><name sortKey="Kobinger, Gary P" sort="Kobinger, Gary P" uniqKey="Kobinger G" first="Gary P." last="Kobinger">Gary P. Kobinger</name><name sortKey="Kung, Sam K P" sort="Kung, Sam K P" uniqKey="Kung S" first="Sam K. P." last="Kung">Sam K. P. Kung</name><name sortKey="Kusalik, Anthony" sort="Kusalik, Anthony" uniqKey="Kusalik A" first="Anthony" last="Kusalik">Anthony Kusalik</name><name sortKey="Patel, Ami" sort="Patel, Ami" uniqKey="Patel A" first="Ami" last="Patel">Ami Patel</name><name sortKey="Richardson, Jason S" sort="Richardson, Jason S" uniqKey="Richardson J" first="Jason S." last="Richardson">Jason S. Richardson</name><name sortKey="Tohme, Sarah" sort="Tohme, Sarah" uniqKey="Tohme S" first="Sarah" last="Tohme">Sarah Tohme</name><name sortKey="Trost, Brett" sort="Trost, Brett" uniqKey="Trost B" first="Brett" last="Trost">Brett Trost</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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