Sublingual immunization of trivalent human papillomavirus DNA vaccine in baculovirus nanovector for protection against vaginal challenge

Here, we report the immunogenicity of a sublingually delivered, trivalent human papillomavirus (HPV) DNA vaccine encapsidated in a human endogenous retrovirus (HERV) envelope-coated, nonreplicable, baculovirus nanovector. The HERV envelope-coated, nonreplicable, baculovirus-based DNA vaccine, encodi...

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Veröffentlicht in:PloS one 2015-03, Vol.10 (3), p.e0119408-e0119408
Hauptverfasser: Lee, Hee-Jung, Cho, Hansam, Kim, Mi-Gyeong, Heo, Yoon-Ki, Cho, Yeondong, Gwon, Yong-Dae, Park, Ki Hoon, Jin, Hyerim, Kim, Jinyoung, Oh, Yu-Kyoung, Kim, Young Bong
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container_start_page e0119408
container_title PloS one
container_volume 10
creator Lee, Hee-Jung
Cho, Hansam
Kim, Mi-Gyeong
Heo, Yoon-Ki
Cho, Yeondong
Gwon, Yong-Dae
Park, Ki Hoon
Jin, Hyerim
Kim, Jinyoung
Oh, Yu-Kyoung
Kim, Young Bong
description Here, we report the immunogenicity of a sublingually delivered, trivalent human papillomavirus (HPV) DNA vaccine encapsidated in a human endogenous retrovirus (HERV) envelope-coated, nonreplicable, baculovirus nanovector. The HERV envelope-coated, nonreplicable, baculovirus-based DNA vaccine, encoding HPV16L1, -18L1 and -58L1 (AcHERV-triHPV), was constructed and sublingually administered to mice without adjuvant. Following sublingual (SL) administration, AcHERV-triHPV was absorbed and distributed throughout the body. At 15 minutes and 1 day post-dose, the distribution of AcHERV-triHPV to the lung was higher than that to other tissues. At 30 days post-dose, the levels of AcHERV-triHPV had diminished throughout the body. Six weeks after the first of three doses, 1×10(8) copies of SL AcHERV-triHPV induced HPV type-specific serum IgG and neutralizing antibodies to a degree comparable to that of IM immunization with 1×10(9) copies. AcHERV-triHPV induced HPV type-specific vaginal IgA titers in a dose-dependent manner. SL immunization with 1×10(10) copies of AcHERV-triHPV induced Th1 and Th2 cellular responses comparable to IM immunization with 1×10(9) copies. Molecular imaging revealed that SL AcHERV-triHPV in mice provided complete protection against vaginal challenge with HPV16, HPV18, and HPV58 pseudoviruses. These results support the potential of SL immunization using multivalent DNA vaccine in baculovirus nanovector for induction of mucosal, systemic, and cellular immune responses.
doi_str_mv 10.1371/journal.pone.0119408
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The HERV envelope-coated, nonreplicable, baculovirus-based DNA vaccine, encoding HPV16L1, -18L1 and -58L1 (AcHERV-triHPV), was constructed and sublingually administered to mice without adjuvant. Following sublingual (SL) administration, AcHERV-triHPV was absorbed and distributed throughout the body. At 15 minutes and 1 day post-dose, the distribution of AcHERV-triHPV to the lung was higher than that to other tissues. At 30 days post-dose, the levels of AcHERV-triHPV had diminished throughout the body. Six weeks after the first of three doses, 1×10(8) copies of SL AcHERV-triHPV induced HPV type-specific serum IgG and neutralizing antibodies to a degree comparable to that of IM immunization with 1×10(9) copies. AcHERV-triHPV induced HPV type-specific vaginal IgA titers in a dose-dependent manner. SL immunization with 1×10(10) copies of AcHERV-triHPV induced Th1 and Th2 cellular responses comparable to IM immunization with 1×10(9) copies. Molecular imaging revealed that SL AcHERV-triHPV in mice provided complete protection against vaginal challenge with HPV16, HPV18, and HPV58 pseudoviruses. These results support the potential of SL immunization using multivalent DNA vaccine in baculovirus nanovector for induction of mucosal, systemic, and cellular immune responses.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0119408</identifier><identifier>PMID: 25789464</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Administration, Sublingual ; Animal tissues ; Animals ; Antibodies ; Antigens ; Baculoviridae - genetics ; Baculovirus ; Capsid Proteins - administration &amp; dosage ; Capsid Proteins - genetics ; Capsid Proteins - immunology ; Cytotoxicity ; Deoxyribonucleic acid ; DNA ; DNA vaccines ; Drug delivery systems ; Female ; Genetic Vectors ; Helper cells ; Human papillomavirus ; Human papillomavirus 16 - genetics ; Human papillomavirus 16 - immunology ; Human papillomavirus 18 - genetics ; Human papillomavirus 18 - immunology ; Humans ; Immune response ; Immune response (cell-mediated) ; Immunity, Cellular - drug effects ; Immunization ; Immunogenicity ; Immunoglobulin A ; Immunoglobulin G ; Laboratory animals ; Lungs ; Lymphocytes T ; Mice ; Mucosal immunity ; Oral administration ; Papillomavirus ; Papillomavirus Infections - immunology ; Papillomavirus Infections - prevention &amp; control ; Papillomavirus Vaccines - administration &amp; dosage ; Papillomavirus Vaccines - immunology ; Pharmaceutical sciences ; Pharmacy ; Proteins ; Rodents ; Studies ; Vaccines ; Vaccines, DNA - administration &amp; dosage ; Vaccines, DNA - immunology ; Vagina ; Vagina - drug effects ; Vagina - immunology ; Viruses</subject><ispartof>PloS one, 2015-03, Vol.10 (3), p.e0119408-e0119408</ispartof><rights>COPYRIGHT 2015 Public Library of Science</rights><rights>2015 Lee et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2015 Lee et al 2015 Lee et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-c8eb417b62684b78068bcf9fa4a1bd23faa69992e485688f47afa51d0dc5b46c3</citedby><cites>FETCH-LOGICAL-c692t-c8eb417b62684b78068bcf9fa4a1bd23faa69992e485688f47afa51d0dc5b46c3</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/PMC4366369/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4366369/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79343,79344</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25789464$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lee, Hee-Jung</creatorcontrib><creatorcontrib>Cho, Hansam</creatorcontrib><creatorcontrib>Kim, Mi-Gyeong</creatorcontrib><creatorcontrib>Heo, Yoon-Ki</creatorcontrib><creatorcontrib>Cho, Yeondong</creatorcontrib><creatorcontrib>Gwon, Yong-Dae</creatorcontrib><creatorcontrib>Park, Ki Hoon</creatorcontrib><creatorcontrib>Jin, Hyerim</creatorcontrib><creatorcontrib>Kim, Jinyoung</creatorcontrib><creatorcontrib>Oh, Yu-Kyoung</creatorcontrib><creatorcontrib>Kim, Young Bong</creatorcontrib><title>Sublingual immunization of trivalent human papillomavirus DNA vaccine in baculovirus nanovector for protection against vaginal challenge</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Here, we report the immunogenicity of a sublingually delivered, trivalent human papillomavirus (HPV) DNA vaccine encapsidated in a human endogenous retrovirus (HERV) envelope-coated, nonreplicable, baculovirus nanovector. The HERV envelope-coated, nonreplicable, baculovirus-based DNA vaccine, encoding HPV16L1, -18L1 and -58L1 (AcHERV-triHPV), was constructed and sublingually administered to mice without adjuvant. Following sublingual (SL) administration, AcHERV-triHPV was absorbed and distributed throughout the body. At 15 minutes and 1 day post-dose, the distribution of AcHERV-triHPV to the lung was higher than that to other tissues. At 30 days post-dose, the levels of AcHERV-triHPV had diminished throughout the body. Six weeks after the first of three doses, 1×10(8) copies of SL AcHERV-triHPV induced HPV type-specific serum IgG and neutralizing antibodies to a degree comparable to that of IM immunization with 1×10(9) copies. AcHERV-triHPV induced HPV type-specific vaginal IgA titers in a dose-dependent manner. SL immunization with 1×10(10) copies of AcHERV-triHPV induced Th1 and Th2 cellular responses comparable to IM immunization with 1×10(9) copies. Molecular imaging revealed that SL AcHERV-triHPV in mice provided complete protection against vaginal challenge with HPV16, HPV18, and HPV58 pseudoviruses. These results support the potential of SL immunization using multivalent DNA vaccine in baculovirus nanovector for induction of mucosal, systemic, and cellular immune responses.</description><subject>Administration, Sublingual</subject><subject>Animal tissues</subject><subject>Animals</subject><subject>Antibodies</subject><subject>Antigens</subject><subject>Baculoviridae - genetics</subject><subject>Baculovirus</subject><subject>Capsid Proteins - administration &amp; dosage</subject><subject>Capsid Proteins - genetics</subject><subject>Capsid Proteins - immunology</subject><subject>Cytotoxicity</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA vaccines</subject><subject>Drug delivery systems</subject><subject>Female</subject><subject>Genetic Vectors</subject><subject>Helper cells</subject><subject>Human papillomavirus</subject><subject>Human papillomavirus 16 - genetics</subject><subject>Human papillomavirus 16 - immunology</subject><subject>Human papillomavirus 18 - genetics</subject><subject>Human papillomavirus 18 - immunology</subject><subject>Humans</subject><subject>Immune response</subject><subject>Immune response (cell-mediated)</subject><subject>Immunity, Cellular - drug effects</subject><subject>Immunization</subject><subject>Immunogenicity</subject><subject>Immunoglobulin A</subject><subject>Immunoglobulin G</subject><subject>Laboratory animals</subject><subject>Lungs</subject><subject>Lymphocytes T</subject><subject>Mice</subject><subject>Mucosal immunity</subject><subject>Oral administration</subject><subject>Papillomavirus</subject><subject>Papillomavirus Infections - immunology</subject><subject>Papillomavirus Infections - prevention &amp; control</subject><subject>Papillomavirus Vaccines - administration &amp; dosage</subject><subject>Papillomavirus Vaccines - immunology</subject><subject>Pharmaceutical sciences</subject><subject>Pharmacy</subject><subject>Proteins</subject><subject>Rodents</subject><subject>Studies</subject><subject>Vaccines</subject><subject>Vaccines, DNA - administration &amp; dosage</subject><subject>Vaccines, DNA - immunology</subject><subject>Vagina</subject><subject>Vagina - drug effects</subject><subject>Vagina - immunology</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>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk9-K1DAUxoso7rr6BqIFQfRixiRN0-RGWNZ_C4sLrnobTtOkkyFNxqQd1Cfwsc3szC4zshdSStvk930n_ZJTFE8xmuOqwW-WYYoe3HwVvJ4jjAVF_F5xjEVFZoyg6v7e-1HxKKUlQnXFGXtYHJG64YIyelz8uZpaZ30_gSvtMEze_obRBl8GU47RrsFpP5aLaQBfrmBlnQsDrG2cUvnu82m5BqWs16X1ZQtqcmE75cGHtVZjiKXJ9yqGMX9tbKEH69OYhb3Nqy_VAlwu0evHxQMDLuknu-dJ8e3D-69nn2YXlx_Pz04vZooJMs4U1y3FTcsI47RtOGK8VUYYoIDbjlQGgAkhiKa8Zpwb2oCBGneoU3VLmapOiudb35ULSe5CTBIzRhtOGsEycb4lugBLuYp2gPhLBrDyeiDEXkIcrXJatpxVhDQ5zNrQDogQGDUYCcxxg6ipstfbXbWpHXSncpgR3IHp4Yy3C9mHtaQVYxUT2eDVziCGH5NOoxxsUto58DpM1-uuMaEE8Yy--Ae9--92VJ-3VlpvQq6rNqbylJKK15yLTdn5HVS-Oj1YlU-csXn8QPD6QJCZUf8ce5hSkudXX_6fvfx-yL7cYxca3LhIwU2bw5QOQboFVQwpRW1uQ8ZIbhrmJg25aRi5a5gse7a_Qbeimw6p_gILHhMv</recordid><startdate>20150319</startdate><enddate>20150319</enddate><creator>Lee, Hee-Jung</creator><creator>Cho, Hansam</creator><creator>Kim, Mi-Gyeong</creator><creator>Heo, Yoon-Ki</creator><creator>Cho, Yeondong</creator><creator>Gwon, Yong-Dae</creator><creator>Park, Ki Hoon</creator><creator>Jin, Hyerim</creator><creator>Kim, Jinyoung</creator><creator>Oh, Yu-Kyoung</creator><creator>Kim, Young Bong</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>IOV</scope><scope>ISR</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>AEUYN</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>COVID</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>20150319</creationdate><title>Sublingual immunization of trivalent human papillomavirus DNA vaccine in baculovirus nanovector for protection against vaginal challenge</title><author>Lee, Hee-Jung ; 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The HERV envelope-coated, nonreplicable, baculovirus-based DNA vaccine, encoding HPV16L1, -18L1 and -58L1 (AcHERV-triHPV), was constructed and sublingually administered to mice without adjuvant. Following sublingual (SL) administration, AcHERV-triHPV was absorbed and distributed throughout the body. At 15 minutes and 1 day post-dose, the distribution of AcHERV-triHPV to the lung was higher than that to other tissues. At 30 days post-dose, the levels of AcHERV-triHPV had diminished throughout the body. Six weeks after the first of three doses, 1×10(8) copies of SL AcHERV-triHPV induced HPV type-specific serum IgG and neutralizing antibodies to a degree comparable to that of IM immunization with 1×10(9) copies. AcHERV-triHPV induced HPV type-specific vaginal IgA titers in a dose-dependent manner. SL immunization with 1×10(10) copies of AcHERV-triHPV induced Th1 and Th2 cellular responses comparable to IM immunization with 1×10(9) copies. Molecular imaging revealed that SL AcHERV-triHPV in mice provided complete protection against vaginal challenge with HPV16, HPV18, and HPV58 pseudoviruses. These results support the potential of SL immunization using multivalent DNA vaccine in baculovirus nanovector for induction of mucosal, systemic, and cellular immune responses.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25789464</pmid><doi>10.1371/journal.pone.0119408</doi><oa>free_for_read</oa></addata></record>
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identifier ISSN: 1932-6203
ispartof PloS one, 2015-03, Vol.10 (3), p.e0119408-e0119408
issn 1932-6203
1932-6203
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source MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS)
subjects Administration, Sublingual
Animal tissues
Animals
Antibodies
Antigens
Baculoviridae - genetics
Baculovirus
Capsid Proteins - administration & dosage
Capsid Proteins - genetics
Capsid Proteins - immunology
Cytotoxicity
Deoxyribonucleic acid
DNA
DNA vaccines
Drug delivery systems
Female
Genetic Vectors
Helper cells
Human papillomavirus
Human papillomavirus 16 - genetics
Human papillomavirus 16 - immunology
Human papillomavirus 18 - genetics
Human papillomavirus 18 - immunology
Humans
Immune response
Immune response (cell-mediated)
Immunity, Cellular - drug effects
Immunization
Immunogenicity
Immunoglobulin A
Immunoglobulin G
Laboratory animals
Lungs
Lymphocytes T
Mice
Mucosal immunity
Oral administration
Papillomavirus
Papillomavirus Infections - immunology
Papillomavirus Infections - prevention & control
Papillomavirus Vaccines - administration & dosage
Papillomavirus Vaccines - immunology
Pharmaceutical sciences
Pharmacy
Proteins
Rodents
Studies
Vaccines
Vaccines, DNA - administration & dosage
Vaccines, DNA - immunology
Vagina
Vagina - drug effects
Vagina - immunology
Viruses
title Sublingual immunization of trivalent human papillomavirus DNA vaccine in baculovirus nanovector for protection against vaginal challenge
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