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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Le document en format XML
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<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>
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<author><name sortKey="Lucchese, G" uniqKey="Lucchese G">G Lucchese</name>
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<author><name sortKey="Kusalik, A" uniqKey="Kusalik A">A Kusalik</name>
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<author><name sortKey="Farber, E" uniqKey="Farber E">E Farber</name>
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<author><name sortKey="Kusalik, A" uniqKey="Kusalik A">A Kusalik</name>
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</TEI>
<affiliations><list><country><li>Canada</li>
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<region><li>Manitoba</li>
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<settlement><li>Winnipeg</li>
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<orgName><li>Université du Manitoba</li>
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