Nanoparticle delivery of a tetravalent E protein subunit vaccine induces balanced, type-specific neutralizing antibodies to each dengue virus serotype
Dengue virus (DENV) is the causative agent of dengue fever and dengue hemorrhagic shock syndrome. Dengue vaccine development is challenging because of the need to induce protection against four antigenically distinct DENV serotypes. Recent studies indicate that tetravalent DENV vaccines must induce...
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| creator | Metz, Stefan W Thomas, Ashlie Brackbill, Alex Xianwen, Yi Stone, Michele Horvath, Katie Miley, Michael J Luft, Chris DeSimone, Joseph M Tian, Shaomin de Silva, Aravinda M |
| description | Dengue virus (DENV) is the causative agent of dengue fever and dengue hemorrhagic shock syndrome. Dengue vaccine development is challenging because of the need to induce protection against four antigenically distinct DENV serotypes. Recent studies indicate that tetravalent DENV vaccines must induce balanced, serotype-specific neutralizing antibodies to achieve durable protective immunity against all 4 serotypes. With the leading live attenuated tetravalent DENV vaccines, it has been difficult to achieve balanced and type-specific responses to each serotype, most likely because of unbalanced replication of vaccine viral strains. Here we evaluate a tetravalent DENV protein subunit vaccine, based on recombinant envelope protein (rE) adsorbed to the surface of poly (lactic-co-glycolic acid) (PLGA) nanoparticles for immunogenicity in mice. In monovalent and tetravalent formulations, we show that particulate rE induced higher neutralizing antibody titers compared to the soluble rE antigen alone. Importantly, we show the trend that tetravalent rE adsorbed to nanoparticles stimulated a more balanced serotype specific antibody response to each DENV serotype compared to soluble antigens. Our results demonstrate that tetravalent DENV subunit vaccines displayed on nanoparticles have the potential to overcome unbalanced immunity observed for leading live-attenuated vaccine candidates. |
| doi_str_mv | 10.1371/journal.pntd.0006793 |
| format | Article |
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Dengue vaccine development is challenging because of the need to induce protection against four antigenically distinct DENV serotypes. Recent studies indicate that tetravalent DENV vaccines must induce balanced, serotype-specific neutralizing antibodies to achieve durable protective immunity against all 4 serotypes. With the leading live attenuated tetravalent DENV vaccines, it has been difficult to achieve balanced and type-specific responses to each serotype, most likely because of unbalanced replication of vaccine viral strains. Here we evaluate a tetravalent DENV protein subunit vaccine, based on recombinant envelope protein (rE) adsorbed to the surface of poly (lactic-co-glycolic acid) (PLGA) nanoparticles for immunogenicity in mice. In monovalent and tetravalent formulations, we show that particulate rE induced higher neutralizing antibody titers compared to the soluble rE antigen alone. Importantly, we show the trend that tetravalent rE adsorbed to nanoparticles stimulated a more balanced serotype specific antibody response to each DENV serotype compared to soluble antigens. Our results demonstrate that tetravalent DENV subunit vaccines displayed on nanoparticles have the potential to overcome unbalanced immunity observed for leading live-attenuated vaccine candidates.</description><identifier>ISSN: 1935-2735</identifier><identifier>ISSN: 1935-2727</identifier><identifier>EISSN: 1935-2735</identifier><identifier>DOI: 10.1371/journal.pntd.0006793</identifier><identifier>PMID: 30248097</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animals ; Antibodies ; Antibodies, Neutralizing - blood ; Antibodies, Viral - blood ; Antibody response ; Antigens ; Biology and Life Sciences ; Dengue fever ; Dengue hemorrhagic fever ; Dengue Vaccines - administration & dosage ; Dengue Vaccines - immunology ; Dengue Virus - immunology ; Disease control ; Drug delivery systems ; Engineering and Technology ; Envelope protein ; Female ; Formulations ; Glycolic acid ; Hemorrhagic shock ; Human diseases ; Immunity ; Immunogenicity ; Immunoglobulins ; Immunology ; Infections ; Medicine and Health Sciences ; Mice, Inbred BALB C ; Microbiological strains ; Nanoparticles ; Nanoparticles - administration & dosage ; Neutralizing ; Polylactic Acid-Polyglycolic Acid Copolymer - administration & dosage ; Polylactide-co-glycolide ; Protein expression ; Proteins ; Recombinants ; Serotypes ; Strains ; Tropical diseases ; Vaccine development ; Vaccines ; Vaccines, Subunit - administration & dosage ; Vaccines, Subunit - immunology ; Vaccines, Synthetic - administration & dosage ; Vaccines, Synthetic - immunology ; Vector-borne diseases ; Viral diseases ; Viral envelope proteins ; Viral Structural Proteins - immunology ; Virology ; Viruses ; Zika virus</subject><ispartof>PLoS neglected tropical diseases, 2018-09, Vol.12 (9), p.e0006793</ispartof><rights>2018 Metz 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>2018 Metz et al 2018 Metz et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c526t-ce408bc499ae34bb753181489d86aae7db106074a83801a231c626c1aab46bec3</citedby><cites>FETCH-LOGICAL-c526t-ce408bc499ae34bb753181489d86aae7db106074a83801a231c626c1aab46bec3</cites><orcidid>0000-0002-9249-2844</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6171938/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6171938/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79343,79344</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30248097$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Metz, Stefan W</creatorcontrib><creatorcontrib>Thomas, Ashlie</creatorcontrib><creatorcontrib>Brackbill, Alex</creatorcontrib><creatorcontrib>Xianwen, Yi</creatorcontrib><creatorcontrib>Stone, Michele</creatorcontrib><creatorcontrib>Horvath, Katie</creatorcontrib><creatorcontrib>Miley, Michael J</creatorcontrib><creatorcontrib>Luft, Chris</creatorcontrib><creatorcontrib>DeSimone, Joseph M</creatorcontrib><creatorcontrib>Tian, Shaomin</creatorcontrib><creatorcontrib>de Silva, Aravinda M</creatorcontrib><title>Nanoparticle delivery of a tetravalent E protein subunit vaccine induces balanced, type-specific neutralizing antibodies to each dengue virus serotype</title><title>PLoS neglected tropical diseases</title><addtitle>PLoS Negl Trop Dis</addtitle><description>Dengue virus (DENV) is the causative agent of dengue fever and dengue hemorrhagic shock syndrome. Dengue vaccine development is challenging because of the need to induce protection against four antigenically distinct DENV serotypes. Recent studies indicate that tetravalent DENV vaccines must induce balanced, serotype-specific neutralizing antibodies to achieve durable protective immunity against all 4 serotypes. With the leading live attenuated tetravalent DENV vaccines, it has been difficult to achieve balanced and type-specific responses to each serotype, most likely because of unbalanced replication of vaccine viral strains. Here we evaluate a tetravalent DENV protein subunit vaccine, based on recombinant envelope protein (rE) adsorbed to the surface of poly (lactic-co-glycolic acid) (PLGA) nanoparticles for immunogenicity in mice. In monovalent and tetravalent formulations, we show that particulate rE induced higher neutralizing antibody titers compared to the soluble rE antigen alone. Importantly, we show the trend that tetravalent rE adsorbed to nanoparticles stimulated a more balanced serotype specific antibody response to each DENV serotype compared to soluble antigens. Our results demonstrate that tetravalent DENV subunit vaccines displayed on nanoparticles have the potential to overcome unbalanced immunity observed for leading live-attenuated vaccine candidates.</description><subject>Animals</subject><subject>Antibodies</subject><subject>Antibodies, Neutralizing - blood</subject><subject>Antibodies, Viral - blood</subject><subject>Antibody response</subject><subject>Antigens</subject><subject>Biology and Life Sciences</subject><subject>Dengue fever</subject><subject>Dengue hemorrhagic fever</subject><subject>Dengue Vaccines - administration & dosage</subject><subject>Dengue Vaccines - immunology</subject><subject>Dengue Virus - immunology</subject><subject>Disease control</subject><subject>Drug delivery systems</subject><subject>Engineering and Technology</subject><subject>Envelope protein</subject><subject>Female</subject><subject>Formulations</subject><subject>Glycolic acid</subject><subject>Hemorrhagic shock</subject><subject>Human 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delivery of a tetravalent E protein subunit vaccine induces balanced, type-specific neutralizing antibodies to each dengue virus serotype</title><author>Metz, Stefan W ; Thomas, Ashlie ; Brackbill, Alex ; Xianwen, Yi ; Stone, Michele ; Horvath, Katie ; Miley, Michael J ; Luft, Chris ; DeSimone, Joseph M ; Tian, Shaomin ; de Silva, Aravinda M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c526t-ce408bc499ae34bb753181489d86aae7db106074a83801a231c626c1aab46bec3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Animals</topic><topic>Antibodies</topic><topic>Antibodies, Neutralizing - blood</topic><topic>Antibodies, Viral - blood</topic><topic>Antibody response</topic><topic>Antigens</topic><topic>Biology and Life Sciences</topic><topic>Dengue fever</topic><topic>Dengue hemorrhagic fever</topic><topic>Dengue Vaccines - administration & dosage</topic><topic>Dengue Vaccines - 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Importantly, we show the trend that tetravalent rE adsorbed to nanoparticles stimulated a more balanced serotype specific antibody response to each DENV serotype compared to soluble antigens. Our results demonstrate that tetravalent DENV subunit vaccines displayed on nanoparticles have the potential to overcome unbalanced immunity observed for leading live-attenuated vaccine candidates.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>30248097</pmid><doi>10.1371/journal.pntd.0006793</doi><orcidid>https://orcid.org/0000-0002-9249-2844</orcidid><oa>free_for_read</oa></addata></record> |
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| issn | 1935-2735 1935-2727 1935-2735 |
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| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; PubMed Central Open Access; Public Library of Science (PLoS) |
| subjects | Animals Antibodies Antibodies, Neutralizing - blood Antibodies, Viral - blood Antibody response Antigens Biology and Life Sciences Dengue fever Dengue hemorrhagic fever Dengue Vaccines - administration & dosage Dengue Vaccines - immunology Dengue Virus - immunology Disease control Drug delivery systems Engineering and Technology Envelope protein Female Formulations Glycolic acid Hemorrhagic shock Human diseases Immunity Immunogenicity Immunoglobulins Immunology Infections Medicine and Health Sciences Mice, Inbred BALB C Microbiological strains Nanoparticles Nanoparticles - administration & dosage Neutralizing Polylactic Acid-Polyglycolic Acid Copolymer - administration & dosage Polylactide-co-glycolide Protein expression Proteins Recombinants Serotypes Strains Tropical diseases Vaccine development Vaccines Vaccines, Subunit - administration & dosage Vaccines, Subunit - immunology Vaccines, Synthetic - administration & dosage Vaccines, Synthetic - immunology Vector-borne diseases Viral diseases Viral envelope proteins Viral Structural Proteins - immunology Virology Viruses Zika virus |
| title | Nanoparticle delivery of a tetravalent E protein subunit vaccine induces balanced, type-specific neutralizing antibodies to each dengue virus serotype |
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