A Novel Prime and Boost Regimen of HIV Virus-Like Particles with TLR4 Adjuvant MPLA Induces Th1 Oriented Immune Responses against HIV
HIV virus-like particles (VLPs) present the HIV envelope protein in its native conformation, providing an ideal vaccine antigen. To enhance the immunogenicity of the VLP vaccine, we sought to improve upon two components; the route of administration and the additional adjuvant. Using HIV VLPs, we eva...
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| Veröffentlicht in: | PloS one 2015-08, Vol.10 (8), p.e0136862-e0136862 |
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| creator | Poteet, Ethan Lewis, Phoebe Li, Feng Zhang, Sheng Gu, Jianhua Chen, Changyi Ho, Sam On Do, Thai Chiang, SuMing Fujii, Gary Yao, Qizhi |
| description | HIV virus-like particles (VLPs) present the HIV envelope protein in its native conformation, providing an ideal vaccine antigen. To enhance the immunogenicity of the VLP vaccine, we sought to improve upon two components; the route of administration and the additional adjuvant. Using HIV VLPs, we evaluated sub-cheek as a novel route of vaccine administration when combined with other conventional routes of immunization. Of five combinations of distinct prime and boost sequences, which included sub-cheek, intranasal, and intradermal routes of administration, intranasal prime and sub-cheek boost (IN+SC) resulted in the highest HIV-specific IgG titers among the groups tested. Using the IN+SC regimen we tested the adjuvant VesiVax Conjugatable Adjuvant Lipid Vesicles (CALV) + monophosphoryl lipid A (MPLA) at MPLA concentrations of 0, 7.5, 12.5, and 25 μg/dose in combination with our VLPs. Mice that received 12.5 or 25 μg/dose MPLA had the highest concentrations of Env-specific IgG2c (20.7 and 18.4 μg/ml respectively), which represents a Th1 type of immune response in C57BL/6 mice. This was in sharp contrast to mice which received 0 or 7.5 μg MPLA adjuvant (6.05 and 5.68 μg/ml of IgG2c respectively). In contrast to IgG2c, MPLA had minor effects on Env-specific IgG1; therefore, 12.5 and 25 μg/dose of MPLA induced the optimal IgG1/IgG2c ratio of 1.3. Additionally, the percentage of germinal center B cells increased significantly from 15.4% in the control group to 31.9% in the CALV + 25 μg MPLA group. These mice also had significantly more IL-2 and less IL-4 Env-specific CD8+ T cells than controls, correlating with an increased percentage of Env-specific central memory CD4+ and CD8+ T cells. Our study shows the strong potential of IN+SC as an efficacious route of administration and the effectiveness of VLPs combined with MPLA adjuvant to induce Env specific Th1-oriented HIV-specific immune responses. |
| doi_str_mv | 10.1371/journal.pone.0136862 |
| format | Article |
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To enhance the immunogenicity of the VLP vaccine, we sought to improve upon two components; the route of administration and the additional adjuvant. Using HIV VLPs, we evaluated sub-cheek as a novel route of vaccine administration when combined with other conventional routes of immunization. Of five combinations of distinct prime and boost sequences, which included sub-cheek, intranasal, and intradermal routes of administration, intranasal prime and sub-cheek boost (IN+SC) resulted in the highest HIV-specific IgG titers among the groups tested. Using the IN+SC regimen we tested the adjuvant VesiVax Conjugatable Adjuvant Lipid Vesicles (CALV) + monophosphoryl lipid A (MPLA) at MPLA concentrations of 0, 7.5, 12.5, and 25 μg/dose in combination with our VLPs. Mice that received 12.5 or 25 μg/dose MPLA had the highest concentrations of Env-specific IgG2c (20.7 and 18.4 μg/ml respectively), which represents a Th1 type of immune response in C57BL/6 mice. This was in sharp contrast to mice which received 0 or 7.5 μg MPLA adjuvant (6.05 and 5.68 μg/ml of IgG2c respectively). In contrast to IgG2c, MPLA had minor effects on Env-specific IgG1; therefore, 12.5 and 25 μg/dose of MPLA induced the optimal IgG1/IgG2c ratio of 1.3. Additionally, the percentage of germinal center B cells increased significantly from 15.4% in the control group to 31.9% in the CALV + 25 μg MPLA group. These mice also had significantly more IL-2 and less IL-4 Env-specific CD8+ T cells than controls, correlating with an increased percentage of Env-specific central memory CD4+ and CD8+ T cells. Our study shows the strong potential of IN+SC as an efficacious route of administration and the effectiveness of VLPs combined with MPLA adjuvant to induce Env specific Th1-oriented HIV-specific immune responses.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0136862</identifier><identifier>PMID: 26312747</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adjuvants, Immunologic - administration & dosage ; Adjuvants, Immunologic - pharmacology ; Administration, Intranasal ; AIDS Vaccines - administration & dosage ; AIDS Vaccines - immunology ; Animals ; Antigens ; Binding sites ; CD4 antigen ; CD8 antigen ; CD8-Positive T-Lymphocytes - immunology ; Cheek ; Combined vaccines ; Cytokines ; Drug Administration Routes ; Female ; HIV ; HIV-1 - immunology ; HIV-1 - ultrastructure ; Human immunodeficiency virus ; Immune response ; Immune system ; Immunization ; Immunization, Secondary - methods ; Immunogenicity ; Immunoglobulin G ; Immunoglobulin G - immunology ; Immunoglobulins ; Immunological memory ; Infections ; Influenza ; Injections, Intradermal ; Interleukin 2 ; Interleukin 4 ; Lipid A ; Lipid A - administration & dosage ; Lipid A - analogs & derivatives ; Lymphocytes ; Lymphocytes B ; Lymphocytes T ; Medicine ; Memory cells ; Mice ; Mice, Inbred C57BL ; Monophosphoryl lipid A ; Particle Size ; Protein structure ; Proteins ; Surgery ; Thy-1 Antigens - immunology ; TLR4 protein ; Toll-Like Receptor 4 - immunology ; Toll-like receptors ; Vaccines ; Viral envelope proteins ; Virus-like particles ; Viruses</subject><ispartof>PloS one, 2015-08, Vol.10 (8), p.e0136862-e0136862</ispartof><rights>This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication: https://creativecommons.org/publicdomain/zero/1.0/ (the “License”) Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c526t-11d0563880e0d2cb609bd5ff65e1eb8eb6770e1bb3f6f18cb02e419fed5d4db03</citedby><cites>FETCH-LOGICAL-c526t-11d0563880e0d2cb609bd5ff65e1eb8eb6770e1bb3f6f18cb02e419fed5d4db03</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/PMC4552547/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4552547/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26312747$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Lu, Shan</contributor><creatorcontrib>Poteet, Ethan</creatorcontrib><creatorcontrib>Lewis, Phoebe</creatorcontrib><creatorcontrib>Li, Feng</creatorcontrib><creatorcontrib>Zhang, Sheng</creatorcontrib><creatorcontrib>Gu, Jianhua</creatorcontrib><creatorcontrib>Chen, Changyi</creatorcontrib><creatorcontrib>Ho, Sam On</creatorcontrib><creatorcontrib>Do, Thai</creatorcontrib><creatorcontrib>Chiang, SuMing</creatorcontrib><creatorcontrib>Fujii, Gary</creatorcontrib><creatorcontrib>Yao, Qizhi</creatorcontrib><title>A Novel Prime and Boost Regimen of HIV Virus-Like Particles with TLR4 Adjuvant MPLA Induces Th1 Oriented Immune Responses against HIV</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>HIV virus-like particles (VLPs) present the HIV envelope protein in its native conformation, providing an ideal vaccine antigen. To enhance the immunogenicity of the VLP vaccine, we sought to improve upon two components; the route of administration and the additional adjuvant. Using HIV VLPs, we evaluated sub-cheek as a novel route of vaccine administration when combined with other conventional routes of immunization. Of five combinations of distinct prime and boost sequences, which included sub-cheek, intranasal, and intradermal routes of administration, intranasal prime and sub-cheek boost (IN+SC) resulted in the highest HIV-specific IgG titers among the groups tested. Using the IN+SC regimen we tested the adjuvant VesiVax Conjugatable Adjuvant Lipid Vesicles (CALV) + monophosphoryl lipid A (MPLA) at MPLA concentrations of 0, 7.5, 12.5, and 25 μg/dose in combination with our VLPs. Mice that received 12.5 or 25 μg/dose MPLA had the highest concentrations of Env-specific IgG2c (20.7 and 18.4 μg/ml respectively), which represents a Th1 type of immune response in C57BL/6 mice. 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Our study shows the strong potential of IN+SC as an efficacious route of administration and the effectiveness of VLPs combined with MPLA adjuvant to induce Env specific Th1-oriented HIV-specific immune responses.</description><subject>Adjuvants, Immunologic - administration & dosage</subject><subject>Adjuvants, Immunologic - pharmacology</subject><subject>Administration, Intranasal</subject><subject>AIDS Vaccines - administration & dosage</subject><subject>AIDS Vaccines - immunology</subject><subject>Animals</subject><subject>Antigens</subject><subject>Binding sites</subject><subject>CD4 antigen</subject><subject>CD8 antigen</subject><subject>CD8-Positive T-Lymphocytes - immunology</subject><subject>Cheek</subject><subject>Combined vaccines</subject><subject>Cytokines</subject><subject>Drug Administration Routes</subject><subject>Female</subject><subject>HIV</subject><subject>HIV-1 - immunology</subject><subject>HIV-1 - ultrastructure</subject><subject>Human immunodeficiency virus</subject><subject>Immune response</subject><subject>Immune system</subject><subject>Immunization</subject><subject>Immunization, Secondary - methods</subject><subject>Immunogenicity</subject><subject>Immunoglobulin G</subject><subject>Immunoglobulin G - immunology</subject><subject>Immunoglobulins</subject><subject>Immunological memory</subject><subject>Infections</subject><subject>Influenza</subject><subject>Injections, Intradermal</subject><subject>Interleukin 2</subject><subject>Interleukin 4</subject><subject>Lipid A</subject><subject>Lipid A - administration & dosage</subject><subject>Lipid A - analogs & derivatives</subject><subject>Lymphocytes</subject><subject>Lymphocytes B</subject><subject>Lymphocytes T</subject><subject>Medicine</subject><subject>Memory cells</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Monophosphoryl lipid A</subject><subject>Particle Size</subject><subject>Protein structure</subject><subject>Proteins</subject><subject>Surgery</subject><subject>Thy-1 Antigens - immunology</subject><subject>TLR4 protein</subject><subject>Toll-Like Receptor 4 - immunology</subject><subject>Toll-like receptors</subject><subject>Vaccines</subject><subject>Viral envelope proteins</subject><subject>Virus-like particles</subject><subject>Viruses</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</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>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNptUl1v0zAUjRCIjcE_QGCJF15S_BE7zgtSmYBFCqyayl4tJ75pU1K72Emn_QD-Ny7Npg3xZOuec8899-okyWuCZ4Tl5MPGjd7qfrZzFmaYMCEFfZKckoLRVFDMnj74nyQvQthgzJkU4nlyQgUjNM_y0-T3HH13e-jRwndbQNoa9Mm5MKArWMWCRa5FF-U1uu78GNKq-wloof3QNT0EdNMNa7SsrjI0N5txr-2Avi2qOSqtGZuIL9cEXfoO7AAGldvtaCHqhug4RFSvdGfjpCj_MnnW6j7Aq-k9S358-bw8v0iry6_l-bxKG07FkBJiMBdMSgzY0KYWuKgNb1vBgUAtoRZ5joHUNWtFS2RTYwoZKVow3GSmxuwseXvU3fUuqOmCQZEcSy7ygsrIKI8M4_RG7eJRtL9VTnfqb8H5lZrWV5zQhsiMAmuyTJJCCyk1x210kHPTiqj1cZo21lswTbyD1_0j0ceI7dZq5fYq45zyLI8C7ycB736NEAa17UIDfa8tuPHoWxaS8AP13T_U_2-XHVmNdyF4aO_NEKwOqbrrUodUqSlVse3Nw0Xum-5ixP4AZhPKFA</recordid><startdate>20150827</startdate><enddate>20150827</enddate><creator>Poteet, Ethan</creator><creator>Lewis, Phoebe</creator><creator>Li, Feng</creator><creator>Zhang, Sheng</creator><creator>Gu, Jianhua</creator><creator>Chen, Changyi</creator><creator>Ho, Sam On</creator><creator>Do, Thai</creator><creator>Chiang, SuMing</creator><creator>Fujii, Gary</creator><creator>Yao, Qizhi</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>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20150827</creationdate><title>A Novel Prime and Boost Regimen of HIV Virus-Like Particles with TLR4 Adjuvant MPLA Induces Th1 Oriented Immune Responses against HIV</title><author>Poteet, Ethan ; Lewis, Phoebe ; Li, Feng ; Zhang, Sheng ; Gu, Jianhua ; Chen, Changyi ; Ho, Sam On ; Do, Thai ; Chiang, SuMing ; Fujii, Gary ; Yao, Qizhi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c526t-11d0563880e0d2cb609bd5ff65e1eb8eb6770e1bb3f6f18cb02e419fed5d4db03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adjuvants, Immunologic - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Poteet, Ethan</au><au>Lewis, Phoebe</au><au>Li, Feng</au><au>Zhang, Sheng</au><au>Gu, Jianhua</au><au>Chen, Changyi</au><au>Ho, Sam On</au><au>Do, Thai</au><au>Chiang, SuMing</au><au>Fujii, Gary</au><au>Yao, Qizhi</au><au>Lu, Shan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A Novel Prime and Boost Regimen of HIV Virus-Like Particles with TLR4 Adjuvant MPLA Induces Th1 Oriented Immune Responses against HIV</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2015-08-27</date><risdate>2015</risdate><volume>10</volume><issue>8</issue><spage>e0136862</spage><epage>e0136862</epage><pages>e0136862-e0136862</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>HIV virus-like particles (VLPs) present the HIV envelope protein in its native conformation, providing an ideal vaccine antigen. To enhance the immunogenicity of the VLP vaccine, we sought to improve upon two components; the route of administration and the additional adjuvant. Using HIV VLPs, we evaluated sub-cheek as a novel route of vaccine administration when combined with other conventional routes of immunization. Of five combinations of distinct prime and boost sequences, which included sub-cheek, intranasal, and intradermal routes of administration, intranasal prime and sub-cheek boost (IN+SC) resulted in the highest HIV-specific IgG titers among the groups tested. Using the IN+SC regimen we tested the adjuvant VesiVax Conjugatable Adjuvant Lipid Vesicles (CALV) + monophosphoryl lipid A (MPLA) at MPLA concentrations of 0, 7.5, 12.5, and 25 μg/dose in combination with our VLPs. Mice that received 12.5 or 25 μg/dose MPLA had the highest concentrations of Env-specific IgG2c (20.7 and 18.4 μg/ml respectively), which represents a Th1 type of immune response in C57BL/6 mice. This was in sharp contrast to mice which received 0 or 7.5 μg MPLA adjuvant (6.05 and 5.68 μg/ml of IgG2c respectively). In contrast to IgG2c, MPLA had minor effects on Env-specific IgG1; therefore, 12.5 and 25 μg/dose of MPLA induced the optimal IgG1/IgG2c ratio of 1.3. Additionally, the percentage of germinal center B cells increased significantly from 15.4% in the control group to 31.9% in the CALV + 25 μg MPLA group. These mice also had significantly more IL-2 and less IL-4 Env-specific CD8+ T cells than controls, correlating with an increased percentage of Env-specific central memory CD4+ and CD8+ T cells. Our study shows the strong potential of IN+SC as an efficacious route of administration and the effectiveness of VLPs combined with MPLA adjuvant to induce Env specific Th1-oriented HIV-specific immune responses.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>26312747</pmid><doi>10.1371/journal.pone.0136862</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2015-08, Vol.10 (8), p.e0136862-e0136862 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1708567928 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Adjuvants, Immunologic - administration & dosage Adjuvants, Immunologic - pharmacology Administration, Intranasal AIDS Vaccines - administration & dosage AIDS Vaccines - immunology Animals Antigens Binding sites CD4 antigen CD8 antigen CD8-Positive T-Lymphocytes - immunology Cheek Combined vaccines Cytokines Drug Administration Routes Female HIV HIV-1 - immunology HIV-1 - ultrastructure Human immunodeficiency virus Immune response Immune system Immunization Immunization, Secondary - methods Immunogenicity Immunoglobulin G Immunoglobulin G - immunology Immunoglobulins Immunological memory Infections Influenza Injections, Intradermal Interleukin 2 Interleukin 4 Lipid A Lipid A - administration & dosage Lipid A - analogs & derivatives Lymphocytes Lymphocytes B Lymphocytes T Medicine Memory cells Mice Mice, Inbred C57BL Monophosphoryl lipid A Particle Size Protein structure Proteins Surgery Thy-1 Antigens - immunology TLR4 protein Toll-Like Receptor 4 - immunology Toll-like receptors Vaccines Viral envelope proteins Virus-like particles Viruses |
| title | A Novel Prime and Boost Regimen of HIV Virus-Like Particles with TLR4 Adjuvant MPLA Induces Th1 Oriented Immune Responses against HIV |
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