Immunogenicity and safety of different injection routes and schedules of IC41, a Hepatitis C virus (HCV) peptide vaccine

Abstract Background An effective vaccine would be a significant progress in the management of chronic HCV infections. This study was designed to examine whether different application schedules and injection routes may enhance the immunogenicity of the HCV peptide vaccine IC41. Methods In this random...

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Veröffentlicht in:Vaccine 2010-03, Vol.28 (12), p.2397-2407
Hauptverfasser: Firbas, Christa, Boehm, Thomas, Buerger, Vera, Schuller, Elisabeth, Sabarth, Nicolas, Jilma, Bernd, Klade, Christoph S
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container_end_page 2407
container_issue 12
container_start_page 2397
container_title Vaccine
container_volume 28
creator Firbas, Christa
Boehm, Thomas
Buerger, Vera
Schuller, Elisabeth
Sabarth, Nicolas
Jilma, Bernd
Klade, Christoph S
description Abstract Background An effective vaccine would be a significant progress in the management of chronic HCV infections. This study was designed to examine whether different application schedules and injection routes may enhance the immunogenicity of the HCV peptide vaccine IC41. Methods In this randomized trial 54 healthy subjects received either subcutaneous (s.c.) or intradermal (i.d.) vaccinations weekly (16 injections) or every other week (8 injections). One group additionally received imiquimod, an activator of the toll-like receptor (TLR) 7. The T cell epitope-specific immune response to IC41 was assessed using [3 H]-thymidine CD4+ T cell proliferation, interferon-gamma (IFN-γ) CD8+ and CD4+ ELIspot and HLA-A*0201 fluorescence-activated cell sorting (FACS) tetramer-binding assays. Results More than 60% of vaccinees responded in the CD4+ T cell proliferation assay in all groups. An HLA-A*0201 FACS tetramer-binding assay and IFN-γ CD8+ ELIspot class I response of more than 70% was induced in four and three groups, respectively. IC41 induced significant immunological responses in all groups with responder rates of up to 100%. Interestingly, topical imiquimod was not able to enhance immunogenicity but was associated with a lower immune response. Local injection site reactions were mostly transient. Intradermal injections caused more pronounced reactions compared to s.c., especially erythema and edema. Conclusion Compared to a previous study intensified dosing and/or i.d. injections enhanced the response rates to the vaccine IC41 in three assays measuring T cell function. Immunization with IC41 was generally safe in this study. These results justify testing IC41 in further clinical trials with HCV-infected individuals.
doi_str_mv 10.1016/j.vaccine.2009.12.072
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This study was designed to examine whether different application schedules and injection routes may enhance the immunogenicity of the HCV peptide vaccine IC41. Methods In this randomized trial 54 healthy subjects received either subcutaneous (s.c.) or intradermal (i.d.) vaccinations weekly (16 injections) or every other week (8 injections). One group additionally received imiquimod, an activator of the toll-like receptor (TLR) 7. The T cell epitope-specific immune response to IC41 was assessed using [3 H]-thymidine CD4+ T cell proliferation, interferon-gamma (IFN-γ) CD8+ and CD4+ ELIspot and HLA-A*0201 fluorescence-activated cell sorting (FACS) tetramer-binding assays. Results More than 60% of vaccinees responded in the CD4+ T cell proliferation assay in all groups. An HLA-A*0201 FACS tetramer-binding assay and IFN-γ CD8+ ELIspot class I response of more than 70% was induced in four and three groups, respectively. IC41 induced significant immunological responses in all groups with responder rates of up to 100%. Interestingly, topical imiquimod was not able to enhance immunogenicity but was associated with a lower immune response. Local injection site reactions were mostly transient. Intradermal injections caused more pronounced reactions compared to s.c., especially erythema and edema. Conclusion Compared to a previous study intensified dosing and/or i.d. injections enhanced the response rates to the vaccine IC41 in three assays measuring T cell function. Immunization with IC41 was generally safe in this study. These results justify testing IC41 in further clinical trials with HCV-infected individuals.</description><identifier>ISSN: 0264-410X</identifier><identifier>EISSN: 1873-2518</identifier><identifier>DOI: 10.1016/j.vaccine.2009.12.072</identifier><identifier>PMID: 20060945</identifier><identifier>CODEN: VACCDE</identifier><language>eng</language><publisher>Kidlington: Elsevier Ltd</publisher><subject>Adjuvants, Immunologic - administration &amp; dosage ; Adjuvants, Immunologic - adverse effects ; Adolescent ; Adult ; Allergy and Immunology ; Aminoquinolines - administration &amp; dosage ; Aminoquinolines - adverse effects ; Applied microbiology ; Biological and medical sciences ; CD4 antigen ; CD4-Positive T-Lymphocytes - immunology ; CD8-Positive T-Lymphocytes - immunology ; Cell growth ; Cell Proliferation ; Chronic illnesses ; Edema ; Female ; Fundamental and applied biological sciences. Psychology ; Healthy subjects ; Hepacivirus - immunology ; Hepatitis ; Hepatitis C vaccine ; Hepatitis C virus ; Human viral diseases ; Humans ; IC41 ; Immune response ; Immune system ; Immunization ; Immunization Schedule ; Immunization, Secondary - methods ; Immunogenicity ; Infections ; Infectious diseases ; Injection ; Injections, Intradermal ; Injections, Subcutaneous ; Interferon-gamma - secretion ; Lymphocytes ; Male ; Medical sciences ; Microbiology ; Middle Aged ; Miscellaneous ; Mortality ; Nutrition research ; Peptides ; Proteins ; Vaccines ; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects) ; Vaccines, Subunit - administration &amp; dosage ; Vaccines, Subunit - adverse effects ; Vaccines, Subunit - immunology ; Viral diseases ; Viral hepatitis ; Viral Hepatitis Vaccines - administration &amp; dosage ; Viral Hepatitis Vaccines - adverse effects ; Viral Hepatitis Vaccines - immunology ; Virology ; Young Adult</subject><ispartof>Vaccine, 2010-03, Vol.28 (12), p.2397-2407</ispartof><rights>Elsevier Ltd</rights><rights>2010 Elsevier Ltd</rights><rights>2015 INIST-CNRS</rights><rights>Copyright Elsevier Limited Mar 11, 2010</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c575t-faba047718c8511e69712baa8abc3ea932f11e4b9d8d2ab36c78487716842c0d3</citedby><cites>FETCH-LOGICAL-c575t-faba047718c8511e69712baa8abc3ea932f11e4b9d8d2ab36c78487716842c0d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0264410X10000083$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=22520486$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20060945$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Firbas, Christa</creatorcontrib><creatorcontrib>Boehm, Thomas</creatorcontrib><creatorcontrib>Buerger, Vera</creatorcontrib><creatorcontrib>Schuller, Elisabeth</creatorcontrib><creatorcontrib>Sabarth, Nicolas</creatorcontrib><creatorcontrib>Jilma, Bernd</creatorcontrib><creatorcontrib>Klade, Christoph S</creatorcontrib><title>Immunogenicity and safety of different injection routes and schedules of IC41, a Hepatitis C virus (HCV) peptide vaccine</title><title>Vaccine</title><addtitle>Vaccine</addtitle><description>Abstract Background An effective vaccine would be a significant progress in the management of chronic HCV infections. This study was designed to examine whether different application schedules and injection routes may enhance the immunogenicity of the HCV peptide vaccine IC41. Methods In this randomized trial 54 healthy subjects received either subcutaneous (s.c.) or intradermal (i.d.) vaccinations weekly (16 injections) or every other week (8 injections). One group additionally received imiquimod, an activator of the toll-like receptor (TLR) 7. The T cell epitope-specific immune response to IC41 was assessed using [3 H]-thymidine CD4+ T cell proliferation, interferon-gamma (IFN-γ) CD8+ and CD4+ ELIspot and HLA-A*0201 fluorescence-activated cell sorting (FACS) tetramer-binding assays. Results More than 60% of vaccinees responded in the CD4+ T cell proliferation assay in all groups. An HLA-A*0201 FACS tetramer-binding assay and IFN-γ CD8+ ELIspot class I response of more than 70% was induced in four and three groups, respectively. IC41 induced significant immunological responses in all groups with responder rates of up to 100%. Interestingly, topical imiquimod was not able to enhance immunogenicity but was associated with a lower immune response. Local injection site reactions were mostly transient. Intradermal injections caused more pronounced reactions compared to s.c., especially erythema and edema. Conclusion Compared to a previous study intensified dosing and/or i.d. injections enhanced the response rates to the vaccine IC41 in three assays measuring T cell function. Immunization with IC41 was generally safe in this study. 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Psychology</subject><subject>Healthy subjects</subject><subject>Hepacivirus - immunology</subject><subject>Hepatitis</subject><subject>Hepatitis C vaccine</subject><subject>Hepatitis C virus</subject><subject>Human viral diseases</subject><subject>Humans</subject><subject>IC41</subject><subject>Immune response</subject><subject>Immune system</subject><subject>Immunization</subject><subject>Immunization Schedule</subject><subject>Immunization, Secondary - methods</subject><subject>Immunogenicity</subject><subject>Infections</subject><subject>Infectious diseases</subject><subject>Injection</subject><subject>Injections, Intradermal</subject><subject>Injections, Subcutaneous</subject><subject>Interferon-gamma - secretion</subject><subject>Lymphocytes</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Microbiology</subject><subject>Middle Aged</subject><subject>Miscellaneous</subject><subject>Mortality</subject><subject>Nutrition research</subject><subject>Peptides</subject><subject>Proteins</subject><subject>Vaccines</subject><subject>Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects)</subject><subject>Vaccines, Subunit - administration &amp; 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Boehm, Thomas ; Buerger, Vera ; Schuller, Elisabeth ; Sabarth, Nicolas ; Jilma, Bernd ; Klade, Christoph S</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c575t-faba047718c8511e69712baa8abc3ea932f11e4b9d8d2ab36c78487716842c0d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Adjuvants, Immunologic - administration &amp; dosage</topic><topic>Adjuvants, Immunologic - adverse effects</topic><topic>Adolescent</topic><topic>Adult</topic><topic>Allergy and Immunology</topic><topic>Aminoquinolines - administration &amp; dosage</topic><topic>Aminoquinolines - adverse effects</topic><topic>Applied microbiology</topic><topic>Biological and medical sciences</topic><topic>CD4 antigen</topic><topic>CD4-Positive T-Lymphocytes - immunology</topic><topic>CD8-Positive T-Lymphocytes - immunology</topic><topic>Cell growth</topic><topic>Cell Proliferation</topic><topic>Chronic illnesses</topic><topic>Edema</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Healthy subjects</topic><topic>Hepacivirus - immunology</topic><topic>Hepatitis</topic><topic>Hepatitis C vaccine</topic><topic>Hepatitis C virus</topic><topic>Human viral diseases</topic><topic>Humans</topic><topic>IC41</topic><topic>Immune response</topic><topic>Immune system</topic><topic>Immunization</topic><topic>Immunization Schedule</topic><topic>Immunization, Secondary - methods</topic><topic>Immunogenicity</topic><topic>Infections</topic><topic>Infectious diseases</topic><topic>Injection</topic><topic>Injections, Intradermal</topic><topic>Injections, Subcutaneous</topic><topic>Interferon-gamma - secretion</topic><topic>Lymphocytes</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Microbiology</topic><topic>Middle Aged</topic><topic>Miscellaneous</topic><topic>Mortality</topic><topic>Nutrition research</topic><topic>Peptides</topic><topic>Proteins</topic><topic>Vaccines</topic><topic>Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects)</topic><topic>Vaccines, Subunit - administration &amp; 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Medical Complete (Alumni)</collection><collection>Nursing &amp; Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Consumer Health Database</collection><collection>Health &amp; 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 &amp; 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>MEDLINE - Academic</collection><jtitle>Vaccine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Firbas, Christa</au><au>Boehm, Thomas</au><au>Buerger, Vera</au><au>Schuller, Elisabeth</au><au>Sabarth, Nicolas</au><au>Jilma, Bernd</au><au>Klade, Christoph S</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Immunogenicity and safety of different injection routes and schedules of IC41, a Hepatitis C virus (HCV) peptide vaccine</atitle><jtitle>Vaccine</jtitle><addtitle>Vaccine</addtitle><date>2010-03-11</date><risdate>2010</risdate><volume>28</volume><issue>12</issue><spage>2397</spage><epage>2407</epage><pages>2397-2407</pages><issn>0264-410X</issn><eissn>1873-2518</eissn><coden>VACCDE</coden><abstract>Abstract Background An effective vaccine would be a significant progress in the management of chronic HCV infections. This study was designed to examine whether different application schedules and injection routes may enhance the immunogenicity of the HCV peptide vaccine IC41. Methods In this randomized trial 54 healthy subjects received either subcutaneous (s.c.) or intradermal (i.d.) vaccinations weekly (16 injections) or every other week (8 injections). One group additionally received imiquimod, an activator of the toll-like receptor (TLR) 7. The T cell epitope-specific immune response to IC41 was assessed using [3 H]-thymidine CD4+ T cell proliferation, interferon-gamma (IFN-γ) CD8+ and CD4+ ELIspot and HLA-A*0201 fluorescence-activated cell sorting (FACS) tetramer-binding assays. Results More than 60% of vaccinees responded in the CD4+ T cell proliferation assay in all groups. An HLA-A*0201 FACS tetramer-binding assay and IFN-γ CD8+ ELIspot class I response of more than 70% was induced in four and three groups, respectively. IC41 induced significant immunological responses in all groups with responder rates of up to 100%. Interestingly, topical imiquimod was not able to enhance immunogenicity but was associated with a lower immune response. Local injection site reactions were mostly transient. Intradermal injections caused more pronounced reactions compared to s.c., especially erythema and edema. Conclusion Compared to a previous study intensified dosing and/or i.d. injections enhanced the response rates to the vaccine IC41 in three assays measuring T cell function. Immunization with IC41 was generally safe in this study. These results justify testing IC41 in further clinical trials with HCV-infected individuals.</abstract><cop>Kidlington</cop><pub>Elsevier Ltd</pub><pmid>20060945</pmid><doi>10.1016/j.vaccine.2009.12.072</doi><tpages>11</tpages></addata></record>
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subjects Adjuvants, Immunologic - administration & dosage
Adjuvants, Immunologic - adverse effects
Adolescent
Adult
Allergy and Immunology
Aminoquinolines - administration & dosage
Aminoquinolines - adverse effects
Applied microbiology
Biological and medical sciences
CD4 antigen
CD4-Positive T-Lymphocytes - immunology
CD8-Positive T-Lymphocytes - immunology
Cell growth
Cell Proliferation
Chronic illnesses
Edema
Female
Fundamental and applied biological sciences. Psychology
Healthy subjects
Hepacivirus - immunology
Hepatitis
Hepatitis C vaccine
Hepatitis C virus
Human viral diseases
Humans
IC41
Immune response
Immune system
Immunization
Immunization Schedule
Immunization, Secondary - methods
Immunogenicity
Infections
Infectious diseases
Injection
Injections, Intradermal
Injections, Subcutaneous
Interferon-gamma - secretion
Lymphocytes
Male
Medical sciences
Microbiology
Middle Aged
Miscellaneous
Mortality
Nutrition research
Peptides
Proteins
Vaccines
Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects)
Vaccines, Subunit - administration & dosage
Vaccines, Subunit - adverse effects
Vaccines, Subunit - immunology
Viral diseases
Viral hepatitis
Viral Hepatitis Vaccines - administration & dosage
Viral Hepatitis Vaccines - adverse effects
Viral Hepatitis Vaccines - immunology
Virology
Young Adult
title Immunogenicity and safety of different injection routes and schedules of IC41, a Hepatitis C virus (HCV) peptide vaccine
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