Immunogenicity in mice and rabbits of DNA vaccines expressing woodchuck hepatitis virus antigens

Abstract The licensed vaccine against hepatitis B virus (HBV) is an effective means to prevent infection, but is not an effective therapeutic strategy to treat established chronic infections when used alone. In an animal model of chronic HBV infection (the woodchuck experimentally infected with wood...

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Veröffentlicht in:Vaccine 2008-07, Vol.26 (32), p.4025-4033
Hauptverfasser: Luxembourg, Alain, Hannaman, Drew, Wills, Ken, Bernard, Robert, Tennant, Bud C, Menne, Stephan, Cote, Paul J
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container_end_page 4033
container_issue 32
container_start_page 4025
container_title Vaccine
container_volume 26
creator Luxembourg, Alain
Hannaman, Drew
Wills, Ken
Bernard, Robert
Tennant, Bud C
Menne, Stephan
Cote, Paul J
description Abstract The licensed vaccine against hepatitis B virus (HBV) is an effective means to prevent infection, but is not an effective therapeutic strategy to treat established chronic infections when used alone. In an animal model of chronic HBV infection (the woodchuck experimentally infected with woodchuck hepatitis virus (WHV)), the combination of conventional vaccine and potent antiviral drugs has shown promise as a potential therapeutic intervention. This approach might be improved further through the application of newer vaccine technologies. In the present study, we evaluated electroporation (EP)-based intramuscular (i.m.) delivery of a codon-optimized DNA vaccine for the WHV surface antigen (WHsAg) in mice and rabbits. In mice, this immunization procedure compared favorably to vaccination by i.m. injection of the DNA vaccine or i.m. administration of a recombinant WHsAg–alum vaccine, exhibiting characteristics expected to be beneficial for a therapeutic vaccine strategy. These included dose efficiency, consistency, vigorous induction of antibody responses to WHsAg, as well as a Th1 bias. Following scale-up to rabbits, a species that approximates the size of the woodchuck, the EP dosing regimen was markedly more effective than conventional i.m. injection of the DNA vaccine. Taken together, these results provide the foundation for studies of EP-based DNA immunization in the woodchuck in order to further assess its potential as an immunotherapeutic approach for treatment of chronic HBV infection in humans.
doi_str_mv 10.1016/j.vaccine.2008.05.021
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In an animal model of chronic HBV infection (the woodchuck experimentally infected with woodchuck hepatitis virus (WHV)), the combination of conventional vaccine and potent antiviral drugs has shown promise as a potential therapeutic intervention. This approach might be improved further through the application of newer vaccine technologies. In the present study, we evaluated electroporation (EP)-based intramuscular (i.m.) delivery of a codon-optimized DNA vaccine for the WHV surface antigen (WHsAg) in mice and rabbits. In mice, this immunization procedure compared favorably to vaccination by i.m. injection of the DNA vaccine or i.m. administration of a recombinant WHsAg–alum vaccine, exhibiting characteristics expected to be beneficial for a therapeutic vaccine strategy. These included dose efficiency, consistency, vigorous induction of antibody responses to WHsAg, as well as a Th1 bias. Following scale-up to rabbits, a species that approximates the size of the woodchuck, the EP dosing regimen was markedly more effective than conventional i.m. injection of the DNA vaccine. Taken together, these results provide the foundation for studies of EP-based DNA immunization in the woodchuck in order to further assess its potential as an immunotherapeutic approach for treatment of chronic HBV infection in humans.</description><identifier>ISSN: 0264-410X</identifier><identifier>EISSN: 1873-2518</identifier><identifier>DOI: 10.1016/j.vaccine.2008.05.021</identifier><identifier>PMID: 18556096</identifier><identifier>CODEN: VACCDE</identifier><language>eng</language><publisher>Oxford: Elsevier Ltd</publisher><subject>Allergy and Immunology ; Animal models ; Animals ; Applied microbiology ; Biological and medical sciences ; Deoxyribonucleic acid ; Disease ; DNA ; DNA vaccine ; Drug resistance ; Electroporation ; Female ; Fundamental and applied biological sciences. Psychology ; Gene Expression Regulation - immunology ; Hepatitis ; Hepatitis B Antibodies - blood ; Hepatitis B Surface Antigens - chemistry ; Hepatitis B Surface Antigens - immunology ; Hepatitis B Vaccines - immunology ; Hepatitis B Vaccines - therapeutic use ; Hepatitis B virus ; Hepatitis B Virus, Woodchuck - immunology ; Immunization ; Immunogenicity ; Immunoglobulin G - blood ; Infections ; Injection ; Laboratory animals ; Lymphocytes ; Marmota - immunology ; Methods ; Mice ; Mice, Inbred BALB C ; Microbiology ; Miscellaneous ; Rabbits ; Vaccines ; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects) ; Vaccines, DNA - immunology ; Vaccines, DNA - therapeutic use ; Virology ; Woodchuck ; Woodchuck hepatitis virus</subject><ispartof>Vaccine, 2008-07, Vol.26 (32), p.4025-4033</ispartof><rights>Elsevier Ltd</rights><rights>2008 Elsevier Ltd</rights><rights>2008 INIST-CNRS</rights><rights>Copyright Elsevier Limited Jul 29, 2008</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c507t-93836ac02cb4bd278b59bac730f66d52403fa572a8bc8873c87c33e12723786f3</citedby><cites>FETCH-LOGICAL-c507t-93836ac02cb4bd278b59bac730f66d52403fa572a8bc8873c87c33e12723786f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.proquest.com/docview/1558848435?pq-origsite=primo$$EHTML$$P50$$Gproquest$$H</linktohtml><link.rule.ids>314,776,780,3536,27903,27904,64361,64363,64365,65309,72215</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=20557508$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18556096$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Luxembourg, Alain</creatorcontrib><creatorcontrib>Hannaman, Drew</creatorcontrib><creatorcontrib>Wills, Ken</creatorcontrib><creatorcontrib>Bernard, Robert</creatorcontrib><creatorcontrib>Tennant, Bud C</creatorcontrib><creatorcontrib>Menne, Stephan</creatorcontrib><creatorcontrib>Cote, Paul J</creatorcontrib><title>Immunogenicity in mice and rabbits of DNA vaccines expressing woodchuck hepatitis virus antigens</title><title>Vaccine</title><addtitle>Vaccine</addtitle><description>Abstract The licensed vaccine against hepatitis B virus (HBV) is an effective means to prevent infection, but is not an effective therapeutic strategy to treat established chronic infections when used alone. In an animal model of chronic HBV infection (the woodchuck experimentally infected with woodchuck hepatitis virus (WHV)), the combination of conventional vaccine and potent antiviral drugs has shown promise as a potential therapeutic intervention. This approach might be improved further through the application of newer vaccine technologies. In the present study, we evaluated electroporation (EP)-based intramuscular (i.m.) delivery of a codon-optimized DNA vaccine for the WHV surface antigen (WHsAg) in mice and rabbits. In mice, this immunization procedure compared favorably to vaccination by i.m. injection of the DNA vaccine or i.m. administration of a recombinant WHsAg–alum vaccine, exhibiting characteristics expected to be beneficial for a therapeutic vaccine strategy. These included dose efficiency, consistency, vigorous induction of antibody responses to WHsAg, as well as a Th1 bias. Following scale-up to rabbits, a species that approximates the size of the woodchuck, the EP dosing regimen was markedly more effective than conventional i.m. injection of the DNA vaccine. Taken together, these results provide the foundation for studies of EP-based DNA immunization in the woodchuck in order to further assess its potential as an immunotherapeutic approach for treatment of chronic HBV infection in humans.</description><subject>Allergy and Immunology</subject><subject>Animal models</subject><subject>Animals</subject><subject>Applied microbiology</subject><subject>Biological and medical sciences</subject><subject>Deoxyribonucleic acid</subject><subject>Disease</subject><subject>DNA</subject><subject>DNA vaccine</subject><subject>Drug resistance</subject><subject>Electroporation</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. 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source MEDLINE; Elsevier ScienceDirect Journals; ProQuest Central UK/Ireland
subjects Allergy and Immunology
Animal models
Animals
Applied microbiology
Biological and medical sciences
Deoxyribonucleic acid
Disease
DNA
DNA vaccine
Drug resistance
Electroporation
Female
Fundamental and applied biological sciences. Psychology
Gene Expression Regulation - immunology
Hepatitis
Hepatitis B Antibodies - blood
Hepatitis B Surface Antigens - chemistry
Hepatitis B Surface Antigens - immunology
Hepatitis B Vaccines - immunology
Hepatitis B Vaccines - therapeutic use
Hepatitis B virus
Hepatitis B Virus, Woodchuck - immunology
Immunization
Immunogenicity
Immunoglobulin G - blood
Infections
Injection
Laboratory animals
Lymphocytes
Marmota - immunology
Methods
Mice
Mice, Inbred BALB C
Microbiology
Miscellaneous
Rabbits
Vaccines
Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects)
Vaccines, DNA - immunology
Vaccines, DNA - therapeutic use
Virology
Woodchuck
Woodchuck hepatitis virus
title Immunogenicity in mice and rabbits of DNA vaccines expressing woodchuck hepatitis virus antigens
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