TLR1/2 activation during heterologous prime-boost vaccination (DNA-MVA) enhances CD8+ T Cell responses providing protection against Leishmania (Viannia)
Leishmania (Viannia) parasites present particular challenges, as human and murine immune responses to infection are distinct from other Leishmania species, indicating a unique interaction with the host. Further, vaccination studies utilizing small animal models indicate that modalities and antigens...
Gespeichert in:
| Veröffentlicht in: | PLoS neglected tropical diseases 2011-06, Vol.5 (6), p.e1204-e1204 |
|---|---|
| Hauptverfasser: | , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | e1204 |
|---|---|
| container_issue | 6 |
| container_start_page | e1204 |
| container_title | PLoS neglected tropical diseases |
| container_volume | 5 |
| creator | Jayakumar, Asha Castilho, Tiago M Park, Esther Goldsmith-Pestana, Karen Blackwell, Jenefer M McMahon-Pratt, Diane |
| description | Leishmania (Viannia) parasites present particular challenges, as human and murine immune responses to infection are distinct from other Leishmania species, indicating a unique interaction with the host. Further, vaccination studies utilizing small animal models indicate that modalities and antigens that prevent infection by other Leishmania species are generally not protective.
Using a newly developed mouse model of chronic L. (Viannia) panamensis infection and the heterologous DNA prime - modified vaccinia virus Ankara (MVA) boost vaccination modality, we examined whether the conserved vaccine candidate antigen tryparedoxin peroxidase (TRYP) could provide protection against infection/disease.
Heterologous prime - boost (DNA/MVA) vaccination utilizing TRYP antigen can provide protection against disease caused by L. (V.) panamensis. However, protection is dependent on modulating the innate immune response using the TLR1/2 agonist Pam3CSK4 during DNA priming. Prime-boost vaccination using DNA alone fails to protect. Prior to infection protectively vaccinated mice exhibit augmented CD4 and CD8 IFNγ and memory responses as well as decreased IL-10 and IL-13 responses. IL-13 and IL-10 have been shown to be independently critical for disease in this model. CD8 T cells have an essential role in mediating host defense, as CD8 depletion reversed protection in the vaccinated mice; vaccinated mice depleted of CD4 T cells remained protected. Hence, vaccine-induced protection is dependent upon TLR1/2 activation instructing the generation of antigen specific CD8 cells and restricting IL-13 and IL-10 responses.
Given the general effectiveness of prime-boost vaccination, the recalcitrance of Leishmania (Viannia) to vaccine approaches effective against other species of Leishmania is again evident. However, prime-boost vaccination modality can with modulation induce protective responses, indicating that the delivery system is critical. Moreover, these results suggest that CD8 T cells should be targeted for the development of a vaccine against infection caused by Leishmania (Viannia) parasites. Further, TLR1/2 modulation may be useful in vaccines where CD8 T cell responses are critical. |
| doi_str_mv | 10.1371/journal.pntd.0001204 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_plos_</sourceid><recordid>TN_cdi_plos_journals_1288103967</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A260691439</galeid><doaj_id>oai_doaj_org_article_6463a2698a0f4010b46fe38f4dca06a9</doaj_id><sourcerecordid>A260691439</sourcerecordid><originalsourceid>FETCH-LOGICAL-c588t-471b89eb7d1998698a09a8b81ab45d13295aaa5effb9b3f092e57f00c47964c23</originalsourceid><addsrcrecordid>eNqFkl1rFDEUhgdRbK3-A9GBgrbIbPM5k9wIy9aPwqoga2_DmUxmJmU2WZOZBf-JP9eZ3W1pRfAqh-Q9T3LevEnyEqMZpgW-uPFDcNDNNq6vZgghTBB7lBxjSXlGCsof36uPkmcx3iDEJRf4aXJEcC45RvQ4-b1afscXJAXd2y301ru0GoJ1Tdqa3gTf-cYPMd0EuzZZ6X3s0y1obd1ee3b5dZ59uZ6fp8a14LSJ6eJSvEtX6cJ0XRpM3HgXzQTwW1tN3LHqjd51QwPWjcSlsbFdg7OQnl1bcGNx_jx5UkMXzYvDepL8-PhhtficLb99ulrMl5nmQvQZK3AppCmLCkspcikASRClwFAyXmFKJAcAbuq6lCWtkSSGFzVCmhUyZ5rQk-T1nrvpfFQHU6PCRIjRIJkXo-Jqr6g83KjJCQi_lAerdhs-NApCb3VnVM5yCmT3ipohjEqW14aKmlUaUA5yZL0_3DaUa1Np4_oA3QPowxNnW9X4raIYs4LjEfD2AAj-52Bir9Y26tFrcGb8KCWkxJwKUvxfWVAmOaGTBad_Kf9tw5u9qoFx0tZA17fRd8P0k1HNSY5yiRmdZmR7oQ4-xmDqu_EwUlN0b_Fqiq46RHdse3Xfmrum26zSP7p57Bk</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1288103967</pqid></control><display><type>article</type><title>TLR1/2 activation during heterologous prime-boost vaccination (DNA-MVA) enhances CD8+ T Cell responses providing protection against Leishmania (Viannia)</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central Open Access</source><source>Public Library of Science (PLoS) Journals Open Access</source><source>PubMed Central</source><creator>Jayakumar, Asha ; Castilho, Tiago M ; Park, Esther ; Goldsmith-Pestana, Karen ; Blackwell, Jenefer M ; McMahon-Pratt, Diane</creator><contributor>Buxbaum, Laurence U.</contributor><creatorcontrib>Jayakumar, Asha ; Castilho, Tiago M ; Park, Esther ; Goldsmith-Pestana, Karen ; Blackwell, Jenefer M ; McMahon-Pratt, Diane ; Buxbaum, Laurence U.</creatorcontrib><description>Leishmania (Viannia) parasites present particular challenges, as human and murine immune responses to infection are distinct from other Leishmania species, indicating a unique interaction with the host. Further, vaccination studies utilizing small animal models indicate that modalities and antigens that prevent infection by other Leishmania species are generally not protective.
Using a newly developed mouse model of chronic L. (Viannia) panamensis infection and the heterologous DNA prime - modified vaccinia virus Ankara (MVA) boost vaccination modality, we examined whether the conserved vaccine candidate antigen tryparedoxin peroxidase (TRYP) could provide protection against infection/disease.
Heterologous prime - boost (DNA/MVA) vaccination utilizing TRYP antigen can provide protection against disease caused by L. (V.) panamensis. However, protection is dependent on modulating the innate immune response using the TLR1/2 agonist Pam3CSK4 during DNA priming. Prime-boost vaccination using DNA alone fails to protect. Prior to infection protectively vaccinated mice exhibit augmented CD4 and CD8 IFNγ and memory responses as well as decreased IL-10 and IL-13 responses. IL-13 and IL-10 have been shown to be independently critical for disease in this model. CD8 T cells have an essential role in mediating host defense, as CD8 depletion reversed protection in the vaccinated mice; vaccinated mice depleted of CD4 T cells remained protected. Hence, vaccine-induced protection is dependent upon TLR1/2 activation instructing the generation of antigen specific CD8 cells and restricting IL-13 and IL-10 responses.
Given the general effectiveness of prime-boost vaccination, the recalcitrance of Leishmania (Viannia) to vaccine approaches effective against other species of Leishmania is again evident. However, prime-boost vaccination modality can with modulation induce protective responses, indicating that the delivery system is critical. Moreover, these results suggest that CD8 T cells should be targeted for the development of a vaccine against infection caused by Leishmania (Viannia) parasites. Further, TLR1/2 modulation may be useful in vaccines where CD8 T cell responses are critical.</description><identifier>ISSN: 1935-2735</identifier><identifier>ISSN: 1935-2727</identifier><identifier>EISSN: 1935-2735</identifier><identifier>DOI: 10.1371/journal.pntd.0001204</identifier><identifier>PMID: 21695103</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject><![CDATA[Animal models ; Animals ; Biology ; CD4-Positive T-Lymphocytes - immunology ; CD8-Positive T-Lymphocytes - immunology ; Deoxyribonucleic acid ; Disease Models, Animal ; DNA ; Female ; Genetic Vectors ; Immune response ; Immune system ; Immunization, Secondary - methods ; Immunology ; Infections ; Interferon-gamma - secretion ; Interleukin-10 - secretion ; Interleukin-13 - secretion ; Leishmania ; Leishmania - genetics ; Leishmania - immunology ; Leishmaniasis ; Leishmaniasis - immunology ; Leishmaniasis - prevention & control ; Leishmaniasis Vaccines - administration & dosage ; Leishmaniasis Vaccines - immunology ; Mice ; Mice, Inbred BALB C ; Parasites ; Peroxidases - genetics ; Peroxidases - immunology ; Prevention ; Protected species ; Protozoan Proteins - genetics ; Protozoan Proteins - immunology ; Risk factors ; Rodent Diseases - immunology ; Rodent Diseases - prevention & control ; Toll-Like Receptor 1 - immunology ; Toll-Like Receptor 2 - immunology ; Tropical diseases ; Vaccination ; Vaccination - methods ; Vaccines ; Vaccines, DNA - administration & dosage ; Vaccines, DNA - immunology ; Vaccines, Synthetic - administration & dosage ; Vaccines, Synthetic - immunology ; Vaccinia virus ; Vaccinia virus - genetics ; Viannia ; Viral Vaccines - administration & dosage ; Viral Vaccines - immunology]]></subject><ispartof>PLoS neglected tropical diseases, 2011-06, Vol.5 (6), p.e1204-e1204</ispartof><rights>COPYRIGHT 2011 Public Library of Science</rights><rights>2011 Jayakumar et al. 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 credited: Jayakumar A, Castilho TM, Park E, Goldsmith-Pestana K, Blackwell JM, et al. (2011) TLR1/2 Activation during Heterologous Prime-Boost Vaccination (DNA-MVA) Enhances CD8+ T Cell Responses Providing Protection against Leishmania (Viannia). PLoS Negl Trop Dis 5(6): e1204. doi:10.1371/journal.pntd.0001204</rights><rights>Jayakumar et al. 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c588t-471b89eb7d1998698a09a8b81ab45d13295aaa5effb9b3f092e57f00c47964c23</citedby><cites>FETCH-LOGICAL-c588t-471b89eb7d1998698a09a8b81ab45d13295aaa5effb9b3f092e57f00c47964c23</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/PMC3114751/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3114751/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,729,782,786,866,887,2106,2932,23875,27933,27934,53800,53802</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21695103$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Buxbaum, Laurence U.</contributor><creatorcontrib>Jayakumar, Asha</creatorcontrib><creatorcontrib>Castilho, Tiago M</creatorcontrib><creatorcontrib>Park, Esther</creatorcontrib><creatorcontrib>Goldsmith-Pestana, Karen</creatorcontrib><creatorcontrib>Blackwell, Jenefer M</creatorcontrib><creatorcontrib>McMahon-Pratt, Diane</creatorcontrib><title>TLR1/2 activation during heterologous prime-boost vaccination (DNA-MVA) enhances CD8+ T Cell responses providing protection against Leishmania (Viannia)</title><title>PLoS neglected tropical diseases</title><addtitle>PLoS Negl Trop Dis</addtitle><description>Leishmania (Viannia) parasites present particular challenges, as human and murine immune responses to infection are distinct from other Leishmania species, indicating a unique interaction with the host. Further, vaccination studies utilizing small animal models indicate that modalities and antigens that prevent infection by other Leishmania species are generally not protective.
Using a newly developed mouse model of chronic L. (Viannia) panamensis infection and the heterologous DNA prime - modified vaccinia virus Ankara (MVA) boost vaccination modality, we examined whether the conserved vaccine candidate antigen tryparedoxin peroxidase (TRYP) could provide protection against infection/disease.
Heterologous prime - boost (DNA/MVA) vaccination utilizing TRYP antigen can provide protection against disease caused by L. (V.) panamensis. However, protection is dependent on modulating the innate immune response using the TLR1/2 agonist Pam3CSK4 during DNA priming. Prime-boost vaccination using DNA alone fails to protect. Prior to infection protectively vaccinated mice exhibit augmented CD4 and CD8 IFNγ and memory responses as well as decreased IL-10 and IL-13 responses. IL-13 and IL-10 have been shown to be independently critical for disease in this model. CD8 T cells have an essential role in mediating host defense, as CD8 depletion reversed protection in the vaccinated mice; vaccinated mice depleted of CD4 T cells remained protected. Hence, vaccine-induced protection is dependent upon TLR1/2 activation instructing the generation of antigen specific CD8 cells and restricting IL-13 and IL-10 responses.
Given the general effectiveness of prime-boost vaccination, the recalcitrance of Leishmania (Viannia) to vaccine approaches effective against other species of Leishmania is again evident. However, prime-boost vaccination modality can with modulation induce protective responses, indicating that the delivery system is critical. Moreover, these results suggest that CD8 T cells should be targeted for the development of a vaccine against infection caused by Leishmania (Viannia) parasites. Further, TLR1/2 modulation may be useful in vaccines where CD8 T cell responses are critical.</description><subject>Animal models</subject><subject>Animals</subject><subject>Biology</subject><subject>CD4-Positive T-Lymphocytes - immunology</subject><subject>CD8-Positive T-Lymphocytes - immunology</subject><subject>Deoxyribonucleic acid</subject><subject>Disease Models, Animal</subject><subject>DNA</subject><subject>Female</subject><subject>Genetic Vectors</subject><subject>Immune response</subject><subject>Immune system</subject><subject>Immunization, Secondary - methods</subject><subject>Immunology</subject><subject>Infections</subject><subject>Interferon-gamma - secretion</subject><subject>Interleukin-10 - secretion</subject><subject>Interleukin-13 - secretion</subject><subject>Leishmania</subject><subject>Leishmania - genetics</subject><subject>Leishmania - immunology</subject><subject>Leishmaniasis</subject><subject>Leishmaniasis - immunology</subject><subject>Leishmaniasis - prevention & control</subject><subject>Leishmaniasis Vaccines - administration & dosage</subject><subject>Leishmaniasis Vaccines - immunology</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Parasites</subject><subject>Peroxidases - genetics</subject><subject>Peroxidases - immunology</subject><subject>Prevention</subject><subject>Protected species</subject><subject>Protozoan Proteins - genetics</subject><subject>Protozoan Proteins - immunology</subject><subject>Risk factors</subject><subject>Rodent Diseases - immunology</subject><subject>Rodent Diseases - prevention & control</subject><subject>Toll-Like Receptor 1 - immunology</subject><subject>Toll-Like Receptor 2 - immunology</subject><subject>Tropical diseases</subject><subject>Vaccination</subject><subject>Vaccination - methods</subject><subject>Vaccines</subject><subject>Vaccines, DNA - administration & dosage</subject><subject>Vaccines, DNA - immunology</subject><subject>Vaccines, Synthetic - administration & dosage</subject><subject>Vaccines, Synthetic - immunology</subject><subject>Vaccinia virus</subject><subject>Vaccinia virus - genetics</subject><subject>Viannia</subject><subject>Viral Vaccines - administration & dosage</subject><subject>Viral Vaccines - immunology</subject><issn>1935-2735</issn><issn>1935-2727</issn><issn>1935-2735</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>DOA</sourceid><recordid>eNqFkl1rFDEUhgdRbK3-A9GBgrbIbPM5k9wIy9aPwqoga2_DmUxmJmU2WZOZBf-JP9eZ3W1pRfAqh-Q9T3LevEnyEqMZpgW-uPFDcNDNNq6vZgghTBB7lBxjSXlGCsof36uPkmcx3iDEJRf4aXJEcC45RvQ4-b1afscXJAXd2y301ru0GoJ1Tdqa3gTf-cYPMd0EuzZZ6X3s0y1obd1ee3b5dZ59uZ6fp8a14LSJ6eJSvEtX6cJ0XRpM3HgXzQTwW1tN3LHqjd51QwPWjcSlsbFdg7OQnl1bcGNx_jx5UkMXzYvDepL8-PhhtficLb99ulrMl5nmQvQZK3AppCmLCkspcikASRClwFAyXmFKJAcAbuq6lCWtkSSGFzVCmhUyZ5rQk-T1nrvpfFQHU6PCRIjRIJkXo-Jqr6g83KjJCQi_lAerdhs-NApCb3VnVM5yCmT3ipohjEqW14aKmlUaUA5yZL0_3DaUa1Np4_oA3QPowxNnW9X4raIYs4LjEfD2AAj-52Bir9Y26tFrcGb8KCWkxJwKUvxfWVAmOaGTBad_Kf9tw5u9qoFx0tZA17fRd8P0k1HNSY5yiRmdZmR7oQ4-xmDqu_EwUlN0b_Fqiq46RHdse3Xfmrum26zSP7p57Bk</recordid><startdate>20110601</startdate><enddate>20110601</enddate><creator>Jayakumar, Asha</creator><creator>Castilho, Tiago M</creator><creator>Park, Esther</creator><creator>Goldsmith-Pestana, Karen</creator><creator>Blackwell, Jenefer M</creator><creator>McMahon-Pratt, Diane</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>3V.</scope><scope>7QL</scope><scope>7SS</scope><scope>7T2</scope><scope>7T7</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8C1</scope><scope>8FD</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>F1W</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>H95</scope><scope>H97</scope><scope>K9.</scope><scope>L.G</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7X8</scope><scope>7TM</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20110601</creationdate><title>TLR1/2 activation during heterologous prime-boost vaccination (DNA-MVA) enhances CD8+ T Cell responses providing protection against Leishmania (Viannia)</title><author>Jayakumar, Asha ; Castilho, Tiago M ; Park, Esther ; Goldsmith-Pestana, Karen ; Blackwell, Jenefer M ; McMahon-Pratt, Diane</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c588t-471b89eb7d1998698a09a8b81ab45d13295aaa5effb9b3f092e57f00c47964c23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Animal models</topic><topic>Animals</topic><topic>Biology</topic><topic>CD4-Positive T-Lymphocytes - immunology</topic><topic>CD8-Positive T-Lymphocytes - immunology</topic><topic>Deoxyribonucleic acid</topic><topic>Disease Models, Animal</topic><topic>DNA</topic><topic>Female</topic><topic>Genetic Vectors</topic><topic>Immune response</topic><topic>Immune system</topic><topic>Immunization, Secondary - methods</topic><topic>Immunology</topic><topic>Infections</topic><topic>Interferon-gamma - secretion</topic><topic>Interleukin-10 - secretion</topic><topic>Interleukin-13 - secretion</topic><topic>Leishmania</topic><topic>Leishmania - genetics</topic><topic>Leishmania - immunology</topic><topic>Leishmaniasis</topic><topic>Leishmaniasis - immunology</topic><topic>Leishmaniasis - prevention & control</topic><topic>Leishmaniasis Vaccines - administration & dosage</topic><topic>Leishmaniasis Vaccines - immunology</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Parasites</topic><topic>Peroxidases - genetics</topic><topic>Peroxidases - immunology</topic><topic>Prevention</topic><topic>Protected species</topic><topic>Protozoan Proteins - genetics</topic><topic>Protozoan Proteins - immunology</topic><topic>Risk factors</topic><topic>Rodent Diseases - immunology</topic><topic>Rodent Diseases - prevention & control</topic><topic>Toll-Like Receptor 1 - immunology</topic><topic>Toll-Like Receptor 2 - immunology</topic><topic>Tropical diseases</topic><topic>Vaccination</topic><topic>Vaccination - methods</topic><topic>Vaccines</topic><topic>Vaccines, DNA - administration & dosage</topic><topic>Vaccines, DNA - immunology</topic><topic>Vaccines, Synthetic - administration & dosage</topic><topic>Vaccines, Synthetic - immunology</topic><topic>Vaccinia virus</topic><topic>Vaccinia virus - genetics</topic><topic>Viannia</topic><topic>Viral Vaccines - administration & dosage</topic><topic>Viral Vaccines - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jayakumar, Asha</creatorcontrib><creatorcontrib>Castilho, Tiago M</creatorcontrib><creatorcontrib>Park, Esther</creatorcontrib><creatorcontrib>Goldsmith-Pestana, Karen</creatorcontrib><creatorcontrib>Blackwell, Jenefer M</creatorcontrib><creatorcontrib>McMahon-Pratt, Diane</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Health and Safety Science Abstracts (Full archive)</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>ASFA: Aquatic Sciences and Fisheries Abstracts</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) 1: Biological Sciences & Living Resources</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) 3: Aquatic Pollution & Environmental Quality</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) Professional</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Access via ProQuest (Open Access)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>MEDLINE - Academic</collection><collection>Nucleic Acids Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PLoS neglected tropical diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jayakumar, Asha</au><au>Castilho, Tiago M</au><au>Park, Esther</au><au>Goldsmith-Pestana, Karen</au><au>Blackwell, Jenefer M</au><au>McMahon-Pratt, Diane</au><au>Buxbaum, Laurence U.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>TLR1/2 activation during heterologous prime-boost vaccination (DNA-MVA) enhances CD8+ T Cell responses providing protection against Leishmania (Viannia)</atitle><jtitle>PLoS neglected tropical diseases</jtitle><addtitle>PLoS Negl Trop Dis</addtitle><date>2011-06-01</date><risdate>2011</risdate><volume>5</volume><issue>6</issue><spage>e1204</spage><epage>e1204</epage><pages>e1204-e1204</pages><issn>1935-2735</issn><issn>1935-2727</issn><eissn>1935-2735</eissn><abstract>Leishmania (Viannia) parasites present particular challenges, as human and murine immune responses to infection are distinct from other Leishmania species, indicating a unique interaction with the host. Further, vaccination studies utilizing small animal models indicate that modalities and antigens that prevent infection by other Leishmania species are generally not protective.
Using a newly developed mouse model of chronic L. (Viannia) panamensis infection and the heterologous DNA prime - modified vaccinia virus Ankara (MVA) boost vaccination modality, we examined whether the conserved vaccine candidate antigen tryparedoxin peroxidase (TRYP) could provide protection against infection/disease.
Heterologous prime - boost (DNA/MVA) vaccination utilizing TRYP antigen can provide protection against disease caused by L. (V.) panamensis. However, protection is dependent on modulating the innate immune response using the TLR1/2 agonist Pam3CSK4 during DNA priming. Prime-boost vaccination using DNA alone fails to protect. Prior to infection protectively vaccinated mice exhibit augmented CD4 and CD8 IFNγ and memory responses as well as decreased IL-10 and IL-13 responses. IL-13 and IL-10 have been shown to be independently critical for disease in this model. CD8 T cells have an essential role in mediating host defense, as CD8 depletion reversed protection in the vaccinated mice; vaccinated mice depleted of CD4 T cells remained protected. Hence, vaccine-induced protection is dependent upon TLR1/2 activation instructing the generation of antigen specific CD8 cells and restricting IL-13 and IL-10 responses.
Given the general effectiveness of prime-boost vaccination, the recalcitrance of Leishmania (Viannia) to vaccine approaches effective against other species of Leishmania is again evident. However, prime-boost vaccination modality can with modulation induce protective responses, indicating that the delivery system is critical. Moreover, these results suggest that CD8 T cells should be targeted for the development of a vaccine against infection caused by Leishmania (Viannia) parasites. Further, TLR1/2 modulation may be useful in vaccines where CD8 T cell responses are critical.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>21695103</pmid><doi>10.1371/journal.pntd.0001204</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1935-2735 |
| ispartof | PLoS neglected tropical diseases, 2011-06, Vol.5 (6), p.e1204-e1204 |
| issn | 1935-2735 1935-2727 1935-2735 |
| language | eng |
| recordid | cdi_plos_journals_1288103967 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central Open Access; Public Library of Science (PLoS) Journals Open Access; PubMed Central |
| subjects | Animal models Animals Biology CD4-Positive T-Lymphocytes - immunology CD8-Positive T-Lymphocytes - immunology Deoxyribonucleic acid Disease Models, Animal DNA Female Genetic Vectors Immune response Immune system Immunization, Secondary - methods Immunology Infections Interferon-gamma - secretion Interleukin-10 - secretion Interleukin-13 - secretion Leishmania Leishmania - genetics Leishmania - immunology Leishmaniasis Leishmaniasis - immunology Leishmaniasis - prevention & control Leishmaniasis Vaccines - administration & dosage Leishmaniasis Vaccines - immunology Mice Mice, Inbred BALB C Parasites Peroxidases - genetics Peroxidases - immunology Prevention Protected species Protozoan Proteins - genetics Protozoan Proteins - immunology Risk factors Rodent Diseases - immunology Rodent Diseases - prevention & control Toll-Like Receptor 1 - immunology Toll-Like Receptor 2 - immunology Tropical diseases Vaccination Vaccination - methods Vaccines Vaccines, DNA - administration & dosage Vaccines, DNA - immunology Vaccines, Synthetic - administration & dosage Vaccines, Synthetic - immunology Vaccinia virus Vaccinia virus - genetics Viannia Viral Vaccines - administration & dosage Viral Vaccines - immunology |
| title | TLR1/2 activation during heterologous prime-boost vaccination (DNA-MVA) enhances CD8+ T Cell responses providing protection against Leishmania (Viannia) |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-02T13%3A01%3A38IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=TLR1/2%20activation%20during%20heterologous%20prime-boost%20vaccination%20(DNA-MVA)%20enhances%20CD8+%20T%20Cell%20responses%20providing%20protection%20against%20Leishmania%20(Viannia)&rft.jtitle=PLoS%20neglected%20tropical%20diseases&rft.au=Jayakumar,%20Asha&rft.date=2011-06-01&rft.volume=5&rft.issue=6&rft.spage=e1204&rft.epage=e1204&rft.pages=e1204-e1204&rft.issn=1935-2735&rft.eissn=1935-2735&rft_id=info:doi/10.1371/journal.pntd.0001204&rft_dat=%3Cgale_plos_%3EA260691439%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1288103967&rft_id=info:pmid/21695103&rft_galeid=A260691439&rft_doaj_id=oai_doaj_org_article_6463a2698a0f4010b46fe38f4dca06a9&rfr_iscdi=true |