Pentamers Not Found in the Universal Proteome Can Enhance Antigen Specific Immune Responses and Adjuvant Vaccines
Identifieur interne : 002224 ( Main/Exploration ); précédent : 002223; suivant : 002225Pentamers 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.
Descripteurs français
- KwdFr :
- MESH :
English descriptors
- KwdEn :
- MESH :
- chemical , immunology : Hepatitis B Vaccines, Histocompatibility Antigens Class II, Influenza Vaccines, Proteome.
- immunology : Killer Cells, Natural.
- Animals, Ferrets, Mice, Mice, Inbred BALB C.
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><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Ferrets</term><term>Hepatitis B Vaccines (immunology)</term><term>Histocompatibility Antigens Class II (immunology)</term><term>Influenza Vaccines (immunology)</term><term>Killer Cells, Natural (immunology)</term><term>Mice</term><term>Mice, Inbred BALB C</term><term>Proteome (immunology)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Antigènes d'histocompatibilité de classe II (immunologie)</term><term>Cellules tueuses naturelles (immunologie)</term><term>Furets</term><term>Protéome (immunologie)</term><term>Souris</term><term>Souris de lignée BALB C</term><term>Vaccins anti-hépatite B (immunologie)</term><term>Vaccins antigrippaux (immunologie)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Hepatitis B Vaccines</term><term>Histocompatibility Antigens Class II</term><term>Influenza Vaccines</term><term>Proteome</term></keywords><keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Antigènes d'histocompatibilité de classe II</term><term>Cellules tueuses naturelles</term><term>Protéome</term><term>Vaccins anti-hépatite B</term><term>Vaccins antigrippaux</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Killer Cells, Natural</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Ferrets</term><term>Mice</term><term>Mice, Inbred BALB C</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Furets</term><term>Souris</term><term>Souris de lignée BALB C</term></keywords></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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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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