Glucopyranosyl lipid adjuvant enhances immune response to Ebola virus-like particle vaccine in mice
•GLA-SE combined with EBOV VLP confers lasting protection against ma-EBOV.•GLA-SE inclusion elicits Th1-skewed antibodies.•GLA-SE enhances EBOV-specific polyfunctional T cells. The identification of adjuvants that promote lasting antigen-specific immunity and augment vaccine efficacy are integral to...
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| Veröffentlicht in: | Vaccine 2019-06, Vol.37 (29), p.3902-3910 |
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| creator | Sunay, Melek M.E. Martins, Karen A.O. Steffens, Jesse T. Gregory, Melissa Vantongeren, Sean A. Van Hoeven, Neal Garnes, Preston G. Bavari, Sina |
| description | •GLA-SE combined with EBOV VLP confers lasting protection against ma-EBOV.•GLA-SE inclusion elicits Th1-skewed antibodies.•GLA-SE enhances EBOV-specific polyfunctional T cells.
The identification of adjuvants that promote lasting antigen-specific immunity and augment vaccine efficacy are integral to the development of new protein-based vaccines. The Ebola virus-like particle (VLP) vaccine expressing Ebola virus glycoprotein (GP) and matrix protein (VP40) was used in this study to evaluate the ability of TLR4 agonist glucopyranosyl lipid adjuvant (GLA) formulated in a stable emulsion (SE) to enhance immunogenicity and promote durable protection against mouse-adapted Ebola virus (ma-EBOV). Antibody responses and Ebola-specific T cell responses were evaluated post vaccination. Survival analysis after lethal ma-EBOV challenge was performed 4 weeks and 22 weeks following final vaccination. GLA-SE enhanced EBOV-specific immunity and resulted in long-term protection against challenge with ma-EBOV infection in a mouse model. Specifically, GLA-SE elicited Th1-skewed antibodies and promoted the generation of EBOV GP-specific polyfunctional T cells. These results provide further support for the utility of TLR4 activating GLA-SE-adjuvanted vaccines. |
| doi_str_mv | 10.1016/j.vaccine.2019.05.026 |
| format | Article |
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The identification of adjuvants that promote lasting antigen-specific immunity and augment vaccine efficacy are integral to the development of new protein-based vaccines. The Ebola virus-like particle (VLP) vaccine expressing Ebola virus glycoprotein (GP) and matrix protein (VP40) was used in this study to evaluate the ability of TLR4 agonist glucopyranosyl lipid adjuvant (GLA) formulated in a stable emulsion (SE) to enhance immunogenicity and promote durable protection against mouse-adapted Ebola virus (ma-EBOV). Antibody responses and Ebola-specific T cell responses were evaluated post vaccination. Survival analysis after lethal ma-EBOV challenge was performed 4 weeks and 22 weeks following final vaccination. GLA-SE enhanced EBOV-specific immunity and resulted in long-term protection against challenge with ma-EBOV infection in a mouse model. Specifically, GLA-SE elicited Th1-skewed antibodies and promoted the generation of EBOV GP-specific polyfunctional T cells. These results provide further support for the utility of TLR4 activating GLA-SE-adjuvanted vaccines.</description><identifier>ISSN: 0264-410X</identifier><identifier>EISSN: 1873-2518</identifier><identifier>DOI: 10.1016/j.vaccine.2019.05.026</identifier><identifier>PMID: 31174937</identifier><language>eng</language><publisher>Netherlands: Elsevier Ltd</publisher><subject>Adjuvant ; Adjuvants ; Aluminum ; Antibodies ; Antigens ; Cytokines ; Ebola virus ; Ebolavirus ; Experiments ; FDA approval ; Glycoproteins ; Human papillomavirus ; Immune response ; Immune system ; Immunity ; Immunogenicity ; Immunology ; Infectious diseases ; Laboratory animals ; Lipids ; Lymphocytes ; Lymphocytes T ; Matrix protein ; Medical research ; Personal appearance ; Protection ; Proteins ; Research centers ; Signal transduction ; TLR agonist ; TLR4 protein ; Toll-like receptors ; Vaccine ; Vaccine efficacy ; Vaccines ; Viral infections ; Virus-like particles ; VP40 protein</subject><ispartof>Vaccine, 2019-06, Vol.37 (29), p.3902-3910</ispartof><rights>2019 Elsevier Ltd</rights><rights>Copyright © 2019 Elsevier Ltd. All rights reserved.</rights><rights>2019. Elsevier Ltd</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c393t-c2a2ba7800054551190b780140a201768b94d4e6ac826e9e67e7beaa9927f0903</citedby><cites>FETCH-LOGICAL-c393t-c2a2ba7800054551190b780140a201768b94d4e6ac826e9e67e7beaa9927f0903</cites><orcidid>0000-0001-8424-5635</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.proquest.com/docview/2239149447?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>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31174937$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sunay, Melek M.E.</creatorcontrib><creatorcontrib>Martins, Karen A.O.</creatorcontrib><creatorcontrib>Steffens, Jesse T.</creatorcontrib><creatorcontrib>Gregory, Melissa</creatorcontrib><creatorcontrib>Vantongeren, Sean A.</creatorcontrib><creatorcontrib>Van Hoeven, Neal</creatorcontrib><creatorcontrib>Garnes, Preston G.</creatorcontrib><creatorcontrib>Bavari, Sina</creatorcontrib><title>Glucopyranosyl lipid adjuvant enhances immune response to Ebola virus-like particle vaccine in mice</title><title>Vaccine</title><addtitle>Vaccine</addtitle><description>•GLA-SE combined with EBOV VLP confers lasting protection against ma-EBOV.•GLA-SE inclusion elicits Th1-skewed antibodies.•GLA-SE enhances EBOV-specific polyfunctional T cells.
The identification of adjuvants that promote lasting antigen-specific immunity and augment vaccine efficacy are integral to the development of new protein-based vaccines. The Ebola virus-like particle (VLP) vaccine expressing Ebola virus glycoprotein (GP) and matrix protein (VP40) was used in this study to evaluate the ability of TLR4 agonist glucopyranosyl lipid adjuvant (GLA) formulated in a stable emulsion (SE) to enhance immunogenicity and promote durable protection against mouse-adapted Ebola virus (ma-EBOV). Antibody responses and Ebola-specific T cell responses were evaluated post vaccination. Survival analysis after lethal ma-EBOV challenge was performed 4 weeks and 22 weeks following final vaccination. GLA-SE enhanced EBOV-specific immunity and resulted in long-term protection against challenge with ma-EBOV infection in a mouse model. Specifically, GLA-SE elicited Th1-skewed antibodies and promoted the generation of EBOV GP-specific polyfunctional T cells. These results provide further support for the utility of TLR4 activating GLA-SE-adjuvanted vaccines.</description><subject>Adjuvant</subject><subject>Adjuvants</subject><subject>Aluminum</subject><subject>Antibodies</subject><subject>Antigens</subject><subject>Cytokines</subject><subject>Ebola virus</subject><subject>Ebolavirus</subject><subject>Experiments</subject><subject>FDA approval</subject><subject>Glycoproteins</subject><subject>Human papillomavirus</subject><subject>Immune response</subject><subject>Immune system</subject><subject>Immunity</subject><subject>Immunogenicity</subject><subject>Immunology</subject><subject>Infectious diseases</subject><subject>Laboratory animals</subject><subject>Lipids</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Matrix protein</subject><subject>Medical research</subject><subject>Personal appearance</subject><subject>Protection</subject><subject>Proteins</subject><subject>Research centers</subject><subject>Signal transduction</subject><subject>TLR agonist</subject><subject>TLR4 protein</subject><subject>Toll-like receptors</subject><subject>Vaccine</subject><subject>Vaccine efficacy</subject><subject>Vaccines</subject><subject>Viral infections</subject><subject>Virus-like particles</subject><subject>VP40 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protection against ma-EBOV.•GLA-SE inclusion elicits Th1-skewed antibodies.•GLA-SE enhances EBOV-specific polyfunctional T cells.
The identification of adjuvants that promote lasting antigen-specific immunity and augment vaccine efficacy are integral to the development of new protein-based vaccines. The Ebola virus-like particle (VLP) vaccine expressing Ebola virus glycoprotein (GP) and matrix protein (VP40) was used in this study to evaluate the ability of TLR4 agonist glucopyranosyl lipid adjuvant (GLA) formulated in a stable emulsion (SE) to enhance immunogenicity and promote durable protection against mouse-adapted Ebola virus (ma-EBOV). Antibody responses and Ebola-specific T cell responses were evaluated post vaccination. Survival analysis after lethal ma-EBOV challenge was performed 4 weeks and 22 weeks following final vaccination. GLA-SE enhanced EBOV-specific immunity and resulted in long-term protection against challenge with ma-EBOV infection in a mouse model. Specifically, GLA-SE elicited Th1-skewed antibodies and promoted the generation of EBOV GP-specific polyfunctional T cells. These results provide further support for the utility of TLR4 activating GLA-SE-adjuvanted vaccines.</abstract><cop>Netherlands</cop><pub>Elsevier Ltd</pub><pmid>31174937</pmid><doi>10.1016/j.vaccine.2019.05.026</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0001-8424-5635</orcidid></addata></record> |
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| language | eng |
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| subjects | Adjuvant Adjuvants Aluminum Antibodies Antigens Cytokines Ebola virus Ebolavirus Experiments FDA approval Glycoproteins Human papillomavirus Immune response Immune system Immunity Immunogenicity Immunology Infectious diseases Laboratory animals Lipids Lymphocytes Lymphocytes T Matrix protein Medical research Personal appearance Protection Proteins Research centers Signal transduction TLR agonist TLR4 protein Toll-like receptors Vaccine Vaccine efficacy Vaccines Viral infections Virus-like particles VP40 protein |
| title | Glucopyranosyl lipid adjuvant enhances immune response to Ebola virus-like particle vaccine in mice |
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