A live guinea pig cytomegalovirus vaccine deleted of three putative immune evasion genes is highly attenuated but remains immunogenic in a vaccine/challenge model of congenital cytomegalovirus infection
Abstract Live attenuated vaccines for prevention of congenital cytomegalovirus infections encode numerous immune evasion genes. Their removal could potentially improve vaccine safety and efficacy. To test this hypothesis, three genes encoding MHC class I homologs (presumed NK evasins) were deleted f...
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| Veröffentlicht in: | Vaccine 2009-06, Vol.27 (31), p.4209-4218 |
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| creator | Crumpler, Megan M Choi, K. Yeon McVoy, Michael A Schleiss, Mark R |
| description | Abstract Live attenuated vaccines for prevention of congenital cytomegalovirus infections encode numerous immune evasion genes. Their removal could potentially improve vaccine safety and efficacy. To test this hypothesis, three genes encoding MHC class I homologs (presumed NK evasins) were deleted from the guinea pig cytomegalovirus genome and the resulting virus, 3DX, was evaluated as a live attenuated vaccine in the guinea pig congenital infection model. 3DX was attenuated in vivo but not in vitro . Vaccination with 3DX produced elevated cytokine levels and higher antibody titers than wild type (WT) virus while avidity and neutralizing titers were similar. Protection, assessed by maternal viral loads and pup mortality following pathogenic viral challenge during pregnancy, was comparable between 3DX and WT and significant compared to naïve animals. These results suggest that the safety and perhaps efficacy of live attenuated human cytomegalovirus vaccines could be enhanced by deletion of viral immunomodulatory genes. |
| doi_str_mv | 10.1016/j.vaccine.2009.04.036 |
| format | Article |
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Yeon ; McVoy, Michael A ; Schleiss, Mark R</creator><creatorcontrib>Crumpler, Megan M ; Choi, K. Yeon ; McVoy, Michael A ; Schleiss, Mark R</creatorcontrib><description>Abstract Live attenuated vaccines for prevention of congenital cytomegalovirus infections encode numerous immune evasion genes. Their removal could potentially improve vaccine safety and efficacy. To test this hypothesis, three genes encoding MHC class I homologs (presumed NK evasins) were deleted from the guinea pig cytomegalovirus genome and the resulting virus, 3DX, was evaluated as a live attenuated vaccine in the guinea pig congenital infection model. 3DX was attenuated in vivo but not in vitro . Vaccination with 3DX produced elevated cytokine levels and higher antibody titers than wild type (WT) virus while avidity and neutralizing titers were similar. Protection, assessed by maternal viral loads and pup mortality following pathogenic viral challenge during pregnancy, was comparable between 3DX and WT and significant compared to naïve animals. These results suggest that the safety and perhaps efficacy of live attenuated human cytomegalovirus vaccines could be enhanced by deletion of viral immunomodulatory genes.</description><identifier>ISSN: 0264-410X</identifier><identifier>EISSN: 1873-2518</identifier><identifier>DOI: 10.1016/j.vaccine.2009.04.036</identifier><identifier>PMID: 19389443</identifier><identifier>CODEN: VACCDE</identifier><language>eng</language><publisher>Kidlington: Elsevier Ltd</publisher><subject>Allergy and Immunology ; Amino Acid Sequence ; Animal models ; Animals ; Antibodies, Viral - blood ; Applied microbiology ; Biological and medical sciences ; Congenital cytomegalovirus infection ; Cytokines - secretion ; Cytomegalovirus ; Cytomegalovirus Infections - prevention & control ; Cytomegalovirus vaccines ; Cytomegalovirus Vaccines - genetics ; Cytomegalovirus Vaccines - immunology ; Female ; Fundamental and applied biological sciences. Psychology ; Gene Deletion ; Genes ; Guinea pig cytomegalovirus ; Guinea Pigs ; Human cytomegalovirus ; Immune system ; MHC class I homolog ; Microbiology ; Miscellaneous ; Molecular Sequence Data ; Neutralization Tests ; Pregnancy ; Roseolovirus - genetics ; Roseolovirus - immunology ; Sequence Alignment ; Swine ; Vaccines ; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects) ; Vaccines, Attenuated - genetics ; Vaccines, Attenuated - immunology ; Viral immune evasion ; Viral Proteins - genetics ; Virology ; Virulence Factors - genetics</subject><ispartof>Vaccine, 2009-06, Vol.27 (31), p.4209-4218</ispartof><rights>2009</rights><rights>2009 INIST-CNRS</rights><rights>Copyright Elsevier Limited Jun 24, 2009</rights><rights>2009 Published by Elsevier Ltd. 2009</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c706t-6218d88d9f88ef30acb5a7d669713da8db69321b147cfedd09854c8281e72a233</citedby><cites>FETCH-LOGICAL-c706t-6218d88d9f88ef30acb5a7d669713da8db69321b147cfedd09854c8281e72a233</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0264410X09005817$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=21722917$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19389443$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Crumpler, Megan M</creatorcontrib><creatorcontrib>Choi, K. Yeon</creatorcontrib><creatorcontrib>McVoy, Michael A</creatorcontrib><creatorcontrib>Schleiss, Mark R</creatorcontrib><title>A live guinea pig cytomegalovirus vaccine deleted of three putative immune evasion genes is highly attenuated but remains immunogenic in a vaccine/challenge model of congenital cytomegalovirus infection</title><title>Vaccine</title><addtitle>Vaccine</addtitle><description>Abstract Live attenuated vaccines for prevention of congenital cytomegalovirus infections encode numerous immune evasion genes. Their removal could potentially improve vaccine safety and efficacy. To test this hypothesis, three genes encoding MHC class I homologs (presumed NK evasins) were deleted from the guinea pig cytomegalovirus genome and the resulting virus, 3DX, was evaluated as a live attenuated vaccine in the guinea pig congenital infection model. 3DX was attenuated in vivo but not in vitro . Vaccination with 3DX produced elevated cytokine levels and higher antibody titers than wild type (WT) virus while avidity and neutralizing titers were similar. Protection, assessed by maternal viral loads and pup mortality following pathogenic viral challenge during pregnancy, was comparable between 3DX and WT and significant compared to naïve animals. These results suggest that the safety and perhaps efficacy of live attenuated human cytomegalovirus vaccines could be enhanced by deletion of viral immunomodulatory genes.</description><subject>Allergy and Immunology</subject><subject>Amino Acid Sequence</subject><subject>Animal models</subject><subject>Animals</subject><subject>Antibodies, Viral - blood</subject><subject>Applied microbiology</subject><subject>Biological and medical sciences</subject><subject>Congenital cytomegalovirus infection</subject><subject>Cytokines - secretion</subject><subject>Cytomegalovirus</subject><subject>Cytomegalovirus Infections - prevention & control</subject><subject>Cytomegalovirus vaccines</subject><subject>Cytomegalovirus Vaccines - genetics</subject><subject>Cytomegalovirus Vaccines - immunology</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene Deletion</subject><subject>Genes</subject><subject>Guinea pig cytomegalovirus</subject><subject>Guinea Pigs</subject><subject>Human cytomegalovirus</subject><subject>Immune system</subject><subject>MHC class I homolog</subject><subject>Microbiology</subject><subject>Miscellaneous</subject><subject>Molecular Sequence Data</subject><subject>Neutralization Tests</subject><subject>Pregnancy</subject><subject>Roseolovirus - genetics</subject><subject>Roseolovirus - immunology</subject><subject>Sequence Alignment</subject><subject>Swine</subject><subject>Vaccines</subject><subject>Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects)</subject><subject>Vaccines, Attenuated - genetics</subject><subject>Vaccines, Attenuated - immunology</subject><subject>Viral immune evasion</subject><subject>Viral Proteins - genetics</subject><subject>Virology</subject><subject>Virulence Factors - genetics</subject><issn>0264-410X</issn><issn>1873-2518</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqNk8tu1DAUhiMEoqXwCCBLCHYz9SUXe9OqqrhJlVgAEjvL45xkPDj2YDuR5hV5KhxNaKEsYOWFv_P_5_j8LornBK8JJvX5bj0prY2DNcVYrHG5xqx-UJwS3rAVrQh_WJxiWperkuCvJ8WTGHcY44oR8bg4IYJxUZbstPhxhayZAPVjllJob3qkD8kP0CvrJxPGiBYf1IKFBC3yHUrbAID2Y1JpLjbDMGYAJhWNd6gHBxGZiLam39oDUimBG9VcuxkTCjAo4-KxymfYaGQcUr-MzvVWWQuuBzT4bDobau9mMCn7V3vGdaBT9n1aPOqUjfBsOc-KL2_ffL5-v7r5-O7D9dXNSje4TquaEt5y3oqOc-gYVnpTqaata9EQ1irebmrBKNmQstEdtC0WvCo1p5xAQxVl7Ky4OOrux80ArQaXgrJyH8ygwkF6ZeSfN85sZe8nySomGlFlgdeLQPDfR4hJDiZqsFY58GOUFPNa0Br_B0hKnIfK4Mt74M6PweVXkKQmnPOmKmff6kjp4GMM0N32TLCcQyV3ctmBnEMlcSlzqHLdi98HvqtaUpSBVwugola2C8ppE285ShpKBWkyd3nkIK9nMhBk1AachtaEvEPZevPPVi7uKWhrcoCU_QYHiHdTy0gllp_mHzB_ACxy9nlu4SeZ4AjY</recordid><startdate>20090624</startdate><enddate>20090624</enddate><creator>Crumpler, Megan M</creator><creator>Choi, K. 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Yeon ; McVoy, Michael A ; Schleiss, Mark R</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c706t-6218d88d9f88ef30acb5a7d669713da8db69321b147cfedd09854c8281e72a233</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Allergy and Immunology</topic><topic>Amino Acid Sequence</topic><topic>Animal models</topic><topic>Animals</topic><topic>Antibodies, Viral - blood</topic><topic>Applied microbiology</topic><topic>Biological and medical sciences</topic><topic>Congenital cytomegalovirus infection</topic><topic>Cytokines - secretion</topic><topic>Cytomegalovirus</topic><topic>Cytomegalovirus Infections - prevention & control</topic><topic>Cytomegalovirus vaccines</topic><topic>Cytomegalovirus Vaccines - genetics</topic><topic>Cytomegalovirus Vaccines - immunology</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. 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Yeon</creatorcontrib><creatorcontrib>McVoy, Michael A</creatorcontrib><creatorcontrib>Schleiss, Mark R</creatorcontrib><collection>Pascal-Francis</collection><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>Proquest Nursing & Allied Health Source</collection><collection>Health and Safety Science Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Healthcare Administration Database (Alumni)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>Consumer Health Database (Alumni Edition)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Consumer Health Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Healthcare Administration Database</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Vaccine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Crumpler, Megan M</au><au>Choi, K. Yeon</au><au>McVoy, Michael A</au><au>Schleiss, Mark R</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A live guinea pig cytomegalovirus vaccine deleted of three putative immune evasion genes is highly attenuated but remains immunogenic in a vaccine/challenge model of congenital cytomegalovirus infection</atitle><jtitle>Vaccine</jtitle><addtitle>Vaccine</addtitle><date>2009-06-24</date><risdate>2009</risdate><volume>27</volume><issue>31</issue><spage>4209</spage><epage>4218</epage><pages>4209-4218</pages><issn>0264-410X</issn><eissn>1873-2518</eissn><coden>VACCDE</coden><abstract>Abstract Live attenuated vaccines for prevention of congenital cytomegalovirus infections encode numerous immune evasion genes. Their removal could potentially improve vaccine safety and efficacy. To test this hypothesis, three genes encoding MHC class I homologs (presumed NK evasins) were deleted from the guinea pig cytomegalovirus genome and the resulting virus, 3DX, was evaluated as a live attenuated vaccine in the guinea pig congenital infection model. 3DX was attenuated in vivo but not in vitro . Vaccination with 3DX produced elevated cytokine levels and higher antibody titers than wild type (WT) virus while avidity and neutralizing titers were similar. Protection, assessed by maternal viral loads and pup mortality following pathogenic viral challenge during pregnancy, was comparable between 3DX and WT and significant compared to naïve animals. These results suggest that the safety and perhaps efficacy of live attenuated human cytomegalovirus vaccines could be enhanced by deletion of viral immunomodulatory genes.</abstract><cop>Kidlington</cop><pub>Elsevier Ltd</pub><pmid>19389443</pmid><doi>10.1016/j.vaccine.2009.04.036</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Vaccine, 2009-06, Vol.27 (31), p.4209-4218 |
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| subjects | Allergy and Immunology Amino Acid Sequence Animal models Animals Antibodies, Viral - blood Applied microbiology Biological and medical sciences Congenital cytomegalovirus infection Cytokines - secretion Cytomegalovirus Cytomegalovirus Infections - prevention & control Cytomegalovirus vaccines Cytomegalovirus Vaccines - genetics Cytomegalovirus Vaccines - immunology Female Fundamental and applied biological sciences. Psychology Gene Deletion Genes Guinea pig cytomegalovirus Guinea Pigs Human cytomegalovirus Immune system MHC class I homolog Microbiology Miscellaneous Molecular Sequence Data Neutralization Tests Pregnancy Roseolovirus - genetics Roseolovirus - immunology Sequence Alignment Swine Vaccines Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects) Vaccines, Attenuated - genetics Vaccines, Attenuated - immunology Viral immune evasion Viral Proteins - genetics Virology Virulence Factors - genetics |
| title | A live guinea pig cytomegalovirus vaccine deleted of three putative immune evasion genes is highly attenuated but remains immunogenic in a vaccine/challenge model of congenital cytomegalovirus infection |
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