Immunogenicity and immune modulatory effects of in silico predicted L. donovani candidate peptide vaccines
Visceral leishmaniasis (VL) is a serious parasitic disease for which control measures are limited and drug resistance is increasing. First and second generation vaccine candidates have not been successful. The goal of the present study was to select possibly immunogenic L. donovani donovani GP63 pep...
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| Veröffentlicht in: | Human vaccines & immunotherapeutics 2012-12, Vol.8 (12), p.1769-1774 |
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| creator | Elfaki, Mona E.E. Khalil, Eltahir A.G. De Groot, Anne S. Musa, Ahmed M. Gutierrez, Andres Younis, Brima M. Salih, Kawthar A.M. El-Hassan, Ahmed M. |
| description | Visceral leishmaniasis (VL) is a serious parasitic disease for which control measures are limited and drug resistance is increasing. First and second generation vaccine candidates have not been successful. The goal of the present study was to select possibly immunogenic L. donovani donovani GP63 peptides using immunoinformatics tools and to test their immunogenicity in vitro. The amino acid sequence of L. donovani donovani GP63 [GenBank accession: ACT31401] was screened using the EpiMatrix algorithm for putative T cell epitopes that would bind to the most common HLA class II alleles (DRB1*1101 and DRB1*0804) among at-risk populations. Four T cell epitopes were selected from nine potential candidates. Stimulation of whole blood from healthy volunteers using the peptides separately produced mean IFN-γ and IL-4 levels that were not significantly different from negative controls, while the pooled peptides produced a moderate IFN-γ increase in some volunteers. However, mean IL-10 levels were significantly reduced for all individuals compared with controls. The immunogenicity of these epitopes may be harnessed most effectively in a vaccine delivered in combination with immune-modulating adjuvants. |
| doi_str_mv | 10.4161/hv.21881 |
| format | Article |
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First and second generation vaccine candidates have not been successful. The goal of the present study was to select possibly immunogenic L. donovani donovani GP63 peptides using immunoinformatics tools and to test their immunogenicity in vitro. The amino acid sequence of L. donovani donovani GP63 [GenBank accession: ACT31401] was screened using the EpiMatrix algorithm for putative T cell epitopes that would bind to the most common HLA class II alleles (DRB1*1101 and DRB1*0804) among at-risk populations. Four T cell epitopes were selected from nine potential candidates. Stimulation of whole blood from healthy volunteers using the peptides separately produced mean IFN-γ and IL-4 levels that were not significantly different from negative controls, while the pooled peptides produced a moderate IFN-γ increase in some volunteers. However, mean IL-10 levels were significantly reduced for all individuals compared with controls. The immunogenicity of these epitopes may be harnessed most effectively in a vaccine delivered in combination with immune-modulating adjuvants.</description><identifier>ISSN: 2164-5515</identifier><identifier>EISSN: 2164-554X</identifier><identifier>DOI: 10.4161/hv.21881</identifier><identifier>PMID: 22922767</identifier><language>eng</language><publisher>United States: Taylor & Francis</publisher><subject>Adult ; Binding ; Biology ; Bioscience ; Calcium ; Cancer ; Cell ; Computational Biology ; Cycle ; EpiMatrix ; Epitopes, T-Lymphocyte - genetics ; Epitopes, T-Lymphocyte - immunology ; Female ; Healthy Volunteers ; Humans ; Interferon-gamma - secretion ; Interleukin-10 - secretion ; Landes ; Leishmania donovani - genetics ; Leishmania donovani - immunology ; Leishmaniasis Vaccines - administration & dosage ; Leishmaniasis Vaccines - genetics ; Leishmaniasis Vaccines - immunology ; Male ; Metalloendopeptidases - genetics ; Metalloendopeptidases - immunology ; Organogenesis ; Proteins ; Research Paper ; T cell epitopes ; T-Lymphocytes - immunology ; vaccine ; Vaccines, Subunit - administration & dosage ; Vaccines, Subunit - genetics ; Vaccines, Subunit - immunology ; visceral leishmaniasis ; Young Adult</subject><ispartof>Human vaccines & immunotherapeutics, 2012-12, Vol.8 (12), p.1769-1774</ispartof><rights>Copyright © 2012 Landes Bioscience 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c469t-e0c7e996298c1e7447be4d35a02dbaa0311946b71158bcbb3eb82e36e42f42b63</citedby><cites>FETCH-LOGICAL-c469t-e0c7e996298c1e7447be4d35a02dbaa0311946b71158bcbb3eb82e36e42f42b63</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3656064/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3656064/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22922767$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Elfaki, Mona E.E.</creatorcontrib><creatorcontrib>Khalil, Eltahir A.G.</creatorcontrib><creatorcontrib>De Groot, Anne S.</creatorcontrib><creatorcontrib>Musa, Ahmed M.</creatorcontrib><creatorcontrib>Gutierrez, Andres</creatorcontrib><creatorcontrib>Younis, Brima M.</creatorcontrib><creatorcontrib>Salih, Kawthar A.M.</creatorcontrib><creatorcontrib>El-Hassan, Ahmed M.</creatorcontrib><title>Immunogenicity and immune modulatory effects of in silico predicted L. donovani candidate peptide vaccines</title><title>Human vaccines & immunotherapeutics</title><addtitle>Hum Vaccin Immunother</addtitle><description>Visceral leishmaniasis (VL) is a serious parasitic disease for which control measures are limited and drug resistance is increasing. First and second generation vaccine candidates have not been successful. The goal of the present study was to select possibly immunogenic L. donovani donovani GP63 peptides using immunoinformatics tools and to test their immunogenicity in vitro. The amino acid sequence of L. donovani donovani GP63 [GenBank accession: ACT31401] was screened using the EpiMatrix algorithm for putative T cell epitopes that would bind to the most common HLA class II alleles (DRB1*1101 and DRB1*0804) among at-risk populations. Four T cell epitopes were selected from nine potential candidates. Stimulation of whole blood from healthy volunteers using the peptides separately produced mean IFN-γ and IL-4 levels that were not significantly different from negative controls, while the pooled peptides produced a moderate IFN-γ increase in some volunteers. However, mean IL-10 levels were significantly reduced for all individuals compared with controls. The immunogenicity of these epitopes may be harnessed most effectively in a vaccine delivered in combination with immune-modulating adjuvants.</description><subject>Adult</subject><subject>Binding</subject><subject>Biology</subject><subject>Bioscience</subject><subject>Calcium</subject><subject>Cancer</subject><subject>Cell</subject><subject>Computational Biology</subject><subject>Cycle</subject><subject>EpiMatrix</subject><subject>Epitopes, T-Lymphocyte - genetics</subject><subject>Epitopes, T-Lymphocyte - immunology</subject><subject>Female</subject><subject>Healthy Volunteers</subject><subject>Humans</subject><subject>Interferon-gamma - secretion</subject><subject>Interleukin-10 - secretion</subject><subject>Landes</subject><subject>Leishmania donovani - genetics</subject><subject>Leishmania donovani - immunology</subject><subject>Leishmaniasis Vaccines - administration & dosage</subject><subject>Leishmaniasis Vaccines - genetics</subject><subject>Leishmaniasis Vaccines - immunology</subject><subject>Male</subject><subject>Metalloendopeptidases - genetics</subject><subject>Metalloendopeptidases - immunology</subject><subject>Organogenesis</subject><subject>Proteins</subject><subject>Research Paper</subject><subject>T cell epitopes</subject><subject>T-Lymphocytes - immunology</subject><subject>vaccine</subject><subject>Vaccines, Subunit - administration & dosage</subject><subject>Vaccines, Subunit - genetics</subject><subject>Vaccines, Subunit - immunology</subject><subject>visceral leishmaniasis</subject><subject>Young Adult</subject><issn>2164-5515</issn><issn>2164-554X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU9r3DAQxU1oSUIa6CcoOvayG0mWZftSKKFtAguF0oTehP6MsxNsyZVkh_32dbrJpqWH6iIx-r03I72ieMvoWjDJLrbzmrOmYUfFKWdSrKpK_Hh1OLPqpDhP6Z4uq6ZcSHlcnHDecl7L-rS4vx6GyYc78Ggx74j2juBjCcgQ3NTrHOKOQNeBzYmEjqAnCXu0gYwRHNoMjmzWxAUfZu2R2MUBnc5ARhgzOiCzthY9pDfF6073Cc6f9rPi5vOn75dXq83XL9eXHzcrK2SbV0BtDW0redtYBrUQtQHhykpT7ozWtGSsFdLUjFWNscaUYBoOpQTBO8GNLM-KD3vfcTIDOAs-R92rMeKg404FjervG49bdRdmVcpKUikWg_dPBjH8nCBlNWCy0PfaQ5iSYmXDaNs0NX9BbQwpRegObRhVj-mo7ax-p7Og7_4c6wA-Z7EAF3tg6eMgGQzJIngLLyhl_OqWsrr6pkbXLQr5H8Xz3ysdM9oeDrOUeyH6LsRBP4TYO5X1rg-xi9pbTKr85wW_ABbWw0U</recordid><startdate>20121201</startdate><enddate>20121201</enddate><creator>Elfaki, Mona E.E.</creator><creator>Khalil, Eltahir A.G.</creator><creator>De Groot, Anne S.</creator><creator>Musa, Ahmed M.</creator><creator>Gutierrez, Andres</creator><creator>Younis, Brima M.</creator><creator>Salih, Kawthar A.M.</creator><creator>El-Hassan, Ahmed M.</creator><general>Taylor & Francis</general><general>Landes Bioscience</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20121201</creationdate><title>Immunogenicity and immune modulatory effects of in silico predicted L. donovani candidate peptide vaccines</title><author>Elfaki, Mona E.E. ; Khalil, Eltahir A.G. ; De Groot, Anne S. ; Musa, Ahmed M. ; Gutierrez, Andres ; Younis, Brima M. ; Salih, Kawthar A.M. ; El-Hassan, Ahmed M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c469t-e0c7e996298c1e7447be4d35a02dbaa0311946b71158bcbb3eb82e36e42f42b63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Adult</topic><topic>Binding</topic><topic>Biology</topic><topic>Bioscience</topic><topic>Calcium</topic><topic>Cancer</topic><topic>Cell</topic><topic>Computational Biology</topic><topic>Cycle</topic><topic>EpiMatrix</topic><topic>Epitopes, T-Lymphocyte - genetics</topic><topic>Epitopes, T-Lymphocyte - immunology</topic><topic>Female</topic><topic>Healthy Volunteers</topic><topic>Humans</topic><topic>Interferon-gamma - secretion</topic><topic>Interleukin-10 - secretion</topic><topic>Landes</topic><topic>Leishmania donovani - genetics</topic><topic>Leishmania donovani - immunology</topic><topic>Leishmaniasis Vaccines - administration & dosage</topic><topic>Leishmaniasis Vaccines - genetics</topic><topic>Leishmaniasis Vaccines - immunology</topic><topic>Male</topic><topic>Metalloendopeptidases - genetics</topic><topic>Metalloendopeptidases - immunology</topic><topic>Organogenesis</topic><topic>Proteins</topic><topic>Research Paper</topic><topic>T cell epitopes</topic><topic>T-Lymphocytes - immunology</topic><topic>vaccine</topic><topic>Vaccines, Subunit - administration & dosage</topic><topic>Vaccines, Subunit - genetics</topic><topic>Vaccines, Subunit - immunology</topic><topic>visceral leishmaniasis</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Elfaki, Mona E.E.</creatorcontrib><creatorcontrib>Khalil, Eltahir A.G.</creatorcontrib><creatorcontrib>De Groot, Anne S.</creatorcontrib><creatorcontrib>Musa, Ahmed M.</creatorcontrib><creatorcontrib>Gutierrez, Andres</creatorcontrib><creatorcontrib>Younis, Brima M.</creatorcontrib><creatorcontrib>Salih, Kawthar A.M.</creatorcontrib><creatorcontrib>El-Hassan, Ahmed M.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Human vaccines & immunotherapeutics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Elfaki, Mona E.E.</au><au>Khalil, Eltahir A.G.</au><au>De Groot, Anne S.</au><au>Musa, Ahmed M.</au><au>Gutierrez, Andres</au><au>Younis, Brima M.</au><au>Salih, Kawthar A.M.</au><au>El-Hassan, Ahmed M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Immunogenicity and immune modulatory effects of in silico predicted L. donovani candidate peptide vaccines</atitle><jtitle>Human vaccines & immunotherapeutics</jtitle><addtitle>Hum Vaccin Immunother</addtitle><date>2012-12-01</date><risdate>2012</risdate><volume>8</volume><issue>12</issue><spage>1769</spage><epage>1774</epage><pages>1769-1774</pages><issn>2164-5515</issn><eissn>2164-554X</eissn><abstract>Visceral leishmaniasis (VL) is a serious parasitic disease for which control measures are limited and drug resistance is increasing. First and second generation vaccine candidates have not been successful. The goal of the present study was to select possibly immunogenic L. donovani donovani GP63 peptides using immunoinformatics tools and to test their immunogenicity in vitro. The amino acid sequence of L. donovani donovani GP63 [GenBank accession: ACT31401] was screened using the EpiMatrix algorithm for putative T cell epitopes that would bind to the most common HLA class II alleles (DRB1*1101 and DRB1*0804) among at-risk populations. Four T cell epitopes were selected from nine potential candidates. Stimulation of whole blood from healthy volunteers using the peptides separately produced mean IFN-γ and IL-4 levels that were not significantly different from negative controls, while the pooled peptides produced a moderate IFN-γ increase in some volunteers. However, mean IL-10 levels were significantly reduced for all individuals compared with controls. The immunogenicity of these epitopes may be harnessed most effectively in a vaccine delivered in combination with immune-modulating adjuvants.</abstract><cop>United States</cop><pub>Taylor & Francis</pub><pmid>22922767</pmid><doi>10.4161/hv.21881</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Binding Biology Bioscience Calcium Cancer Cell Computational Biology Cycle EpiMatrix Epitopes, T-Lymphocyte - genetics Epitopes, T-Lymphocyte - immunology Female Healthy Volunteers Humans Interferon-gamma - secretion Interleukin-10 - secretion Landes Leishmania donovani - genetics Leishmania donovani - immunology Leishmaniasis Vaccines - administration & dosage Leishmaniasis Vaccines - genetics Leishmaniasis Vaccines - immunology Male Metalloendopeptidases - genetics Metalloendopeptidases - immunology Organogenesis Proteins Research Paper T cell epitopes T-Lymphocytes - immunology vaccine Vaccines, Subunit - administration & dosage Vaccines, Subunit - genetics Vaccines, Subunit - immunology visceral leishmaniasis Young Adult |
| title | Immunogenicity and immune modulatory effects of in silico predicted L. donovani candidate peptide vaccines |
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