Herpes simplex virus 2 (HSV-2) infected cell proteins are among the most dominant antigens of a live-attenuated HSV-2 vaccine
Virion glycoproteins such as glycoprotein D (gD) are believed to be the dominant antigens of herpes simplex virus 2 (HSV-2). We have observed that mice immunized with a live HSV-2 ICP0- mutant virus, HSV-2 0ΔNLS, are 10 to 100 times better protected against genital herpes than mice immunized with a...
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| description | Virion glycoproteins such as glycoprotein D (gD) are believed to be the dominant antigens of herpes simplex virus 2 (HSV-2). We have observed that mice immunized with a live HSV-2 ICP0- mutant virus, HSV-2 0ΔNLS, are 10 to 100 times better protected against genital herpes than mice immunized with a HSV-2 gD subunit vaccine (PLoS ONE 6:e17748). In light of these results, we sought to determine which viral proteins were the dominant antibody-generators (antigens) of the live HSV-2 0ΔNLS vaccine. Western blot analyses indicated the live HSV-2 0ΔNLS vaccine elicited an IgG antibody response against 9 or more viral proteins. Many antibodies were directed against infected-cell proteins of >100 kDa in size, and only 10 ± 5% of antibodies were directed against gD. Immunoprecipitation (IP) of total HSV-2 antigen with 0ΔNLS antiserum pulled down 19 viral proteins. Mass spectrometry suggested 44% of immunoprecipitated viral peptides were derived from two HSV-2 infected cells proteins, RR-1 and ICP8, whereas only 14% of immunoprecipitated peptides were derived from HSV-2's thirteen glycoproteins. Collectively, the results suggest the immune response to the live HSV-2 0ΔNLS vaccine includes antibodies specific for infected cell proteins, capsid proteins, tegument proteins, and glycoproteins. This increased breadth of antibody-generating proteins may contribute to the live HSV-2 vaccine's capacity to elicit superior protection against genital herpes relative to a gD subunit vaccine. |
| doi_str_mv | 10.1371/journal.pone.0116091 |
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We have observed that mice immunized with a live HSV-2 ICP0- mutant virus, HSV-2 0ΔNLS, are 10 to 100 times better protected against genital herpes than mice immunized with a HSV-2 gD subunit vaccine (PLoS ONE 6:e17748). In light of these results, we sought to determine which viral proteins were the dominant antibody-generators (antigens) of the live HSV-2 0ΔNLS vaccine. Western blot analyses indicated the live HSV-2 0ΔNLS vaccine elicited an IgG antibody response against 9 or more viral proteins. Many antibodies were directed against infected-cell proteins of >100 kDa in size, and only 10 ± 5% of antibodies were directed against gD. Immunoprecipitation (IP) of total HSV-2 antigen with 0ΔNLS antiserum pulled down 19 viral proteins. Mass spectrometry suggested 44% of immunoprecipitated viral peptides were derived from two HSV-2 infected cells proteins, RR-1 and ICP8, whereas only 14% of immunoprecipitated peptides were derived from HSV-2's thirteen glycoproteins. Collectively, the results suggest the immune response to the live HSV-2 0ΔNLS vaccine includes antibodies specific for infected cell proteins, capsid proteins, tegument proteins, and glycoproteins. This increased breadth of antibody-generating proteins may contribute to the live HSV-2 vaccine's capacity to elicit superior protection against genital herpes relative to a gD subunit vaccine.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0116091</identifier><identifier>PMID: 25658852</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Analysis ; Animals ; Antibody response ; Antigens ; Antigens, Viral - genetics ; Antigens, Viral - metabolism ; Artificial chromosomes ; Binding sites ; Gene expression ; Genomes ; Glycoprotein D ; Glycoproteins ; Herpes Genitalis - prevention & control ; Herpes simplex ; Herpes simplex virus ; Herpes Simplex Virus Vaccines - genetics ; Herpes Simplex Virus Vaccines - immunology ; Herpes viruses ; Herpesvirus 2, Human - metabolism ; IgG antibody ; Immune response ; Immune system ; Immunization ; Immunoglobulin G ; Immunoglobulin G - blood ; Immunoglobulins ; Immunology ; Immunoprecipitation ; Laboratories ; Mass Spectrometry ; Mass spectroscopy ; Mice ; Mutation ; Peptides ; Proteins ; Suidae ; Tegument ; Vaccines ; Viral Envelope Proteins - metabolism ; Viral proteins ; Virions ; Virology ; Viruses</subject><ispartof>PloS one, 2015-02, Vol.10 (2), p.e0116091-e0116091</ispartof><rights>COPYRIGHT 2015 Public Library of Science</rights><rights>2015 Geltz 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 Geltz et al 2015 Geltz et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c593t-60b7577d2252f0cae39e7909adb32ab22aaf9156ef1d639632aadb0bb49f24753</citedby><cites>FETCH-LOGICAL-c593t-60b7577d2252f0cae39e7909adb32ab22aaf9156ef1d639632aadb0bb49f24753</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/PMC4319894/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4319894/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2095,2914,23846,27903,27904,53769,53771,79346,79347</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25658852$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>BenMohamed, Lbachir</contributor><creatorcontrib>Geltz, Joshua J</creatorcontrib><creatorcontrib>Gershburg, Edward</creatorcontrib><creatorcontrib>Halford, William P</creatorcontrib><title>Herpes simplex virus 2 (HSV-2) infected cell proteins are among the most dominant antigens of a live-attenuated HSV-2 vaccine</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Virion glycoproteins such as glycoprotein D (gD) are believed to be the dominant antigens of herpes simplex virus 2 (HSV-2). We have observed that mice immunized with a live HSV-2 ICP0- mutant virus, HSV-2 0ΔNLS, are 10 to 100 times better protected against genital herpes than mice immunized with a HSV-2 gD subunit vaccine (PLoS ONE 6:e17748). In light of these results, we sought to determine which viral proteins were the dominant antibody-generators (antigens) of the live HSV-2 0ΔNLS vaccine. Western blot analyses indicated the live HSV-2 0ΔNLS vaccine elicited an IgG antibody response against 9 or more viral proteins. Many antibodies were directed against infected-cell proteins of >100 kDa in size, and only 10 ± 5% of antibodies were directed against gD. Immunoprecipitation (IP) of total HSV-2 antigen with 0ΔNLS antiserum pulled down 19 viral proteins. Mass spectrometry suggested 44% of immunoprecipitated viral peptides were derived from two HSV-2 infected cells proteins, RR-1 and ICP8, whereas only 14% of immunoprecipitated peptides were derived from HSV-2's thirteen glycoproteins. Collectively, the results suggest the immune response to the live HSV-2 0ΔNLS vaccine includes antibodies specific for infected cell proteins, capsid proteins, tegument proteins, and glycoproteins. This increased breadth of antibody-generating proteins may contribute to the live HSV-2 vaccine's capacity to elicit superior protection against genital herpes relative to a gD subunit vaccine.</description><subject>Analysis</subject><subject>Animals</subject><subject>Antibody response</subject><subject>Antigens</subject><subject>Antigens, Viral - genetics</subject><subject>Antigens, Viral - metabolism</subject><subject>Artificial chromosomes</subject><subject>Binding sites</subject><subject>Gene expression</subject><subject>Genomes</subject><subject>Glycoprotein D</subject><subject>Glycoproteins</subject><subject>Herpes Genitalis - prevention & control</subject><subject>Herpes simplex</subject><subject>Herpes simplex virus</subject><subject>Herpes Simplex Virus Vaccines - genetics</subject><subject>Herpes Simplex Virus Vaccines - immunology</subject><subject>Herpes viruses</subject><subject>Herpesvirus 2, Human - metabolism</subject><subject>IgG antibody</subject><subject>Immune response</subject><subject>Immune system</subject><subject>Immunization</subject><subject>Immunoglobulin G</subject><subject>Immunoglobulin G - blood</subject><subject>Immunoglobulins</subject><subject>Immunology</subject><subject>Immunoprecipitation</subject><subject>Laboratories</subject><subject>Mass Spectrometry</subject><subject>Mass spectroscopy</subject><subject>Mice</subject><subject>Mutation</subject><subject>Peptides</subject><subject>Proteins</subject><subject>Suidae</subject><subject>Tegument</subject><subject>Vaccines</subject><subject>Viral Envelope Proteins - metabolism</subject><subject>Viral proteins</subject><subject>Virions</subject><subject>Virology</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>eNptUstu1DAUjRCIloE_QGCJTVlk8CN24g1SVQFTqRILHlvLSW6mHiV2sJ0RLPh3nJm06qDKsmzde-65r5NlrwleE1aSDzs3eav79egsrDEhAkvyJDsnktFcUMyePvifZS9C2GHMWSXE8-yMcsGritPz7O8G_AgBBTOMPfxGe-OngCi62Hz7mdP3yNgOmggtaqDv0ehdBGMD0h6QHpzdongLaHAhotYNxmobUbpmCwnkOqRRb_aQ6xjBTnrmOfCivW4aY-Fl9qzTfYBXy7vKfnz-9P1qk998_XJ9dXmTN1yymAtcl7wsW0o57XCjgUkoJZa6rRnVNaVad5JwAR1pBZMiGZML13UhO1qUnK2yt0fesXdBLZMLighOiZSM04S4PiJap3dq9GbQ_o9y2qiDwfmt0j6apgeV0EJjIBiToqAFkxKgA9YxLCp-zPZxyTbVA7QN2Oh1f0J66rHmVm3dXhWMyEoWieBiIfDu1wQhqsGEeQHagpsOdTNCBSNlgr77D_p4dwtqq1MDaacu5W1mUnVZUFklojToVbZ-BJVOC4Npksw6k-wnAcUxoPEuBA_dfY8Eq1mkd8WoWaRqEWkKe_NwPvdBd6pk_wDkpOKX</recordid><startdate>20150206</startdate><enddate>20150206</enddate><creator>Geltz, Joshua J</creator><creator>Gershburg, Edward</creator><creator>Halford, William P</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>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>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>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20150206</creationdate><title>Herpes simplex virus 2 (HSV-2) infected cell proteins are among the most dominant antigens of a live-attenuated HSV-2 vaccine</title><author>Geltz, Joshua J ; Gershburg, Edward ; Halford, William P</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c593t-60b7577d2252f0cae39e7909adb32ab22aaf9156ef1d639632aadb0bb49f24753</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Analysis</topic><topic>Animals</topic><topic>Antibody response</topic><topic>Antigens</topic><topic>Antigens, Viral - 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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>Geltz, Joshua J</au><au>Gershburg, Edward</au><au>Halford, William P</au><au>BenMohamed, Lbachir</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Herpes simplex virus 2 (HSV-2) infected cell proteins are among the most dominant antigens of a live-attenuated HSV-2 vaccine</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2015-02-06</date><risdate>2015</risdate><volume>10</volume><issue>2</issue><spage>e0116091</spage><epage>e0116091</epage><pages>e0116091-e0116091</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Virion glycoproteins such as glycoprotein D (gD) are believed to be the dominant antigens of herpes simplex virus 2 (HSV-2). We have observed that mice immunized with a live HSV-2 ICP0- mutant virus, HSV-2 0ΔNLS, are 10 to 100 times better protected against genital herpes than mice immunized with a HSV-2 gD subunit vaccine (PLoS ONE 6:e17748). In light of these results, we sought to determine which viral proteins were the dominant antibody-generators (antigens) of the live HSV-2 0ΔNLS vaccine. Western blot analyses indicated the live HSV-2 0ΔNLS vaccine elicited an IgG antibody response against 9 or more viral proteins. Many antibodies were directed against infected-cell proteins of >100 kDa in size, and only 10 ± 5% of antibodies were directed against gD. Immunoprecipitation (IP) of total HSV-2 antigen with 0ΔNLS antiserum pulled down 19 viral proteins. Mass spectrometry suggested 44% of immunoprecipitated viral peptides were derived from two HSV-2 infected cells proteins, RR-1 and ICP8, whereas only 14% of immunoprecipitated peptides were derived from HSV-2's thirteen glycoproteins. Collectively, the results suggest the immune response to the live HSV-2 0ΔNLS vaccine includes antibodies specific for infected cell proteins, capsid proteins, tegument proteins, and glycoproteins. This increased breadth of antibody-generating proteins may contribute to the live HSV-2 vaccine's capacity to elicit superior protection against genital herpes relative to a gD subunit vaccine.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25658852</pmid><doi>10.1371/journal.pone.0116091</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Analysis Animals Antibody response Antigens Antigens, Viral - genetics Antigens, Viral - metabolism Artificial chromosomes Binding sites Gene expression Genomes Glycoprotein D Glycoproteins Herpes Genitalis - prevention & control Herpes simplex Herpes simplex virus Herpes Simplex Virus Vaccines - genetics Herpes Simplex Virus Vaccines - immunology Herpes viruses Herpesvirus 2, Human - metabolism IgG antibody Immune response Immune system Immunization Immunoglobulin G Immunoglobulin G - blood Immunoglobulins Immunology Immunoprecipitation Laboratories Mass Spectrometry Mass spectroscopy Mice Mutation Peptides Proteins Suidae Tegument Vaccines Viral Envelope Proteins - metabolism Viral proteins Virions Virology Viruses |
| title | Herpes simplex virus 2 (HSV-2) infected cell proteins are among the most dominant antigens of a live-attenuated HSV-2 vaccine |
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