An inactivated recombinant rabies virus displaying the Zika virus prM-E induces protective immunity against both pathogens
The global spread of Zika virus (ZIKV), which caused a pandemic associated with Congenital Zika Syndrome and neuropathology in newborns and adults, prompted the pursuit of a safe and effective vaccine. Here, three kinds of recombinant rabies virus (RABV) encoding the prM-E protein of ZIKV were const...
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| Veröffentlicht in: | PLoS neglected tropical diseases 2021-06, Vol.15 (6), p.e0009484-e0009484 |
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| creator | Jin, Hongli Jiao, Cuicui Cao, Zengguo Huang, Pei Chi, Hang Bai, Yujie Liu, Di Wang, Jianzhong Feng, Na Li, Nan Zhao, Yongkun Wang, Tiecheng Gao, Yuwei Yang, Songtao Xia, Xianzhu Wang, Hualei |
| description | The global spread of Zika virus (ZIKV), which caused a pandemic associated with Congenital Zika Syndrome and neuropathology in newborns and adults, prompted the pursuit of a safe and effective vaccine. Here, three kinds of recombinant rabies virus (RABV) encoding the prM-E protein of ZIKV were constructed: ZI-D (prM-E), ZI-E (transmembrane domain (TM) of prM-E replaced with RABV G) and ZI-F (signal peptide and TM domain of prM-E replaced with the region of RABV G). When the TM of prM-E was replaced with the region of RABV G (termed ZI-E), it promoted ZIKV E protein localization on the cell membrane and assembly on recombinant viruses. In addition, the change in the signal peptide with RABV G (termed ZI-F) was not conducive to foreign protein expression. The immunogenicity of recombinant viruses mixed with a complex adjuvant of ISA 201 VG and poly(I:C) was tested in BALB/c mice. After immunization with ZI-E, the anti-ZIKV IgG antibody lasted for at least 10 weeks. The titers of neutralizing antibodies (NAbs) against ZIKV and RABV at week 6 were all greater than the protective titers. Moreover, ZI-E stimulated the proliferation of splenic lymphocytes and promoted the secretion of cytokines. It also promoted the production of central memory T cells (TCMs) among CD4+/CD8+ T cells and stimulated B cell activation and maturation. These results indicate that ZI-E could induce ZIKV-specific humoral and cellular immune responses, which have the potential to be developed into a promising vaccine for protection against both ZIKV and RABV infections. |
| doi_str_mv | 10.1371/journal.pntd.0009484 |
| format | Article |
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Here, three kinds of recombinant rabies virus (RABV) encoding the prM-E protein of ZIKV were constructed: ZI-D (prM-E), ZI-E (transmembrane domain (TM) of prM-E replaced with RABV G) and ZI-F (signal peptide and TM domain of prM-E replaced with the region of RABV G). When the TM of prM-E was replaced with the region of RABV G (termed ZI-E), it promoted ZIKV E protein localization on the cell membrane and assembly on recombinant viruses. In addition, the change in the signal peptide with RABV G (termed ZI-F) was not conducive to foreign protein expression. The immunogenicity of recombinant viruses mixed with a complex adjuvant of ISA 201 VG and poly(I:C) was tested in BALB/c mice. After immunization with ZI-E, the anti-ZIKV IgG antibody lasted for at least 10 weeks. The titers of neutralizing antibodies (NAbs) against ZIKV and RABV at week 6 were all greater than the protective titers. Moreover, ZI-E stimulated the proliferation of splenic lymphocytes and promoted the secretion of cytokines. It also promoted the production of central memory T cells (TCMs) among CD4+/CD8+ T cells and stimulated B cell activation and maturation. These results indicate that ZI-E could induce ZIKV-specific humoral and cellular immune responses, which have the potential to be developed into a promising vaccine for protection against both ZIKV and RABV infections.</description><identifier>ISSN: 1935-2735</identifier><identifier>ISSN: 1935-2727</identifier><identifier>EISSN: 1935-2735</identifier><identifier>DOI: 10.1371/journal.pntd.0009484</identifier><identifier>PMID: 34086672</identifier><language>eng</language><publisher>San Francisco: Public Library of Science</publisher><subject>Adenoviruses ; Adults ; Antibodies ; Biology and Life Sciences ; CD4 antigen ; CD8 antigen ; Cell activation ; Cell membranes ; Cells ; Cytokines ; Disease control ; Domains ; E protein ; Gene expression ; Genetic aspects ; Genetically modified organisms ; Health aspects ; IgG antibody ; Immune response (cell-mediated) ; Immune response (humoral) ; Immunity ; Immunization ; Immunogenicity ; Immunoglobulin G ; Immunological memory ; Immunological research ; Infections ; Laboratory animals ; Localization ; Lymphocytes ; Lymphocytes T ; Lyssavirus ; Medicine and Health Sciences ; Memory cells ; Microscopy ; Neonates ; Pandemics ; Pathogenesis ; Pathogens ; Poly (I:C) ; Polyclonal antibodies ; Polyinosinic:polycytidylic acid ; Prevention ; Proliferation ; Proteins ; Rabies ; Recombinants ; Research and Analysis Methods ; Respiratory diseases ; Secretion ; Spleen ; Tropical diseases ; Vaccines ; Vector-borne diseases ; Viral proteins ; Viral vaccines ; Viruses ; Zika virus</subject><ispartof>PLoS neglected tropical diseases, 2021-06, Vol.15 (6), p.e0009484-e0009484</ispartof><rights>COPYRIGHT 2021 Public Library of Science</rights><rights>2021 Jin 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>2021 Jin et al 2021 Jin et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c601t-be8699847cfd6e691d94ea1c765a3955706806f03edd3cd06bc5d3412cbe81d43</citedby><cites>FETCH-LOGICAL-c601t-be8699847cfd6e691d94ea1c765a3955706806f03edd3cd06bc5d3412cbe81d43</cites><orcidid>0000-0001-6961-1991</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/PMC8208564/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8208564/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids></links><search><creatorcontrib>Jin, Hongli</creatorcontrib><creatorcontrib>Jiao, Cuicui</creatorcontrib><creatorcontrib>Cao, Zengguo</creatorcontrib><creatorcontrib>Huang, Pei</creatorcontrib><creatorcontrib>Chi, Hang</creatorcontrib><creatorcontrib>Bai, Yujie</creatorcontrib><creatorcontrib>Liu, Di</creatorcontrib><creatorcontrib>Wang, Jianzhong</creatorcontrib><creatorcontrib>Feng, Na</creatorcontrib><creatorcontrib>Li, Nan</creatorcontrib><creatorcontrib>Zhao, Yongkun</creatorcontrib><creatorcontrib>Wang, Tiecheng</creatorcontrib><creatorcontrib>Gao, Yuwei</creatorcontrib><creatorcontrib>Yang, Songtao</creatorcontrib><creatorcontrib>Xia, Xianzhu</creatorcontrib><creatorcontrib>Wang, Hualei</creatorcontrib><title>An inactivated recombinant rabies virus displaying the Zika virus prM-E induces protective immunity against both pathogens</title><title>PLoS neglected tropical diseases</title><description>The global spread of Zika virus (ZIKV), which caused a pandemic associated with Congenital Zika Syndrome and neuropathology in newborns and adults, prompted the pursuit of a safe and effective vaccine. Here, three kinds of recombinant rabies virus (RABV) encoding the prM-E protein of ZIKV were constructed: ZI-D (prM-E), ZI-E (transmembrane domain (TM) of prM-E replaced with RABV G) and ZI-F (signal peptide and TM domain of prM-E replaced with the region of RABV G). When the TM of prM-E was replaced with the region of RABV G (termed ZI-E), it promoted ZIKV E protein localization on the cell membrane and assembly on recombinant viruses. In addition, the change in the signal peptide with RABV G (termed ZI-F) was not conducive to foreign protein expression. The immunogenicity of recombinant viruses mixed with a complex adjuvant of ISA 201 VG and poly(I:C) was tested in BALB/c mice. After immunization with ZI-E, the anti-ZIKV IgG antibody lasted for at least 10 weeks. The titers of neutralizing antibodies (NAbs) against ZIKV and RABV at week 6 were all greater than the protective titers. Moreover, ZI-E stimulated the proliferation of splenic lymphocytes and promoted the secretion of cytokines. It also promoted the production of central memory T cells (TCMs) among CD4+/CD8+ T cells and stimulated B cell activation and maturation. These results indicate that ZI-E could induce ZIKV-specific humoral and cellular immune responses, which have the potential to be developed into a promising vaccine for protection against both ZIKV and RABV infections.</description><subject>Adenoviruses</subject><subject>Adults</subject><subject>Antibodies</subject><subject>Biology and Life Sciences</subject><subject>CD4 antigen</subject><subject>CD8 antigen</subject><subject>Cell activation</subject><subject>Cell membranes</subject><subject>Cells</subject><subject>Cytokines</subject><subject>Disease control</subject><subject>Domains</subject><subject>E protein</subject><subject>Gene expression</subject><subject>Genetic aspects</subject><subject>Genetically modified organisms</subject><subject>Health aspects</subject><subject>IgG antibody</subject><subject>Immune response (cell-mediated)</subject><subject>Immune response (humoral)</subject><subject>Immunity</subject><subject>Immunization</subject><subject>Immunogenicity</subject><subject>Immunoglobulin G</subject><subject>Immunological memory</subject><subject>Immunological research</subject><subject>Infections</subject><subject>Laboratory animals</subject><subject>Localization</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Lyssavirus</subject><subject>Medicine and Health Sciences</subject><subject>Memory cells</subject><subject>Microscopy</subject><subject>Neonates</subject><subject>Pandemics</subject><subject>Pathogenesis</subject><subject>Pathogens</subject><subject>Poly (I:C)</subject><subject>Polyclonal antibodies</subject><subject>Polyinosinic:polycytidylic acid</subject><subject>Prevention</subject><subject>Proliferation</subject><subject>Proteins</subject><subject>Rabies</subject><subject>Recombinants</subject><subject>Research and Analysis Methods</subject><subject>Respiratory diseases</subject><subject>Secretion</subject><subject>Spleen</subject><subject>Tropical diseases</subject><subject>Vaccines</subject><subject>Vector-borne diseases</subject><subject>Viral proteins</subject><subject>Viral vaccines</subject><subject>Viruses</subject><subject>Zika 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displaying the Zika virus prM-E induces protective immunity against both pathogens</title><author>Jin, Hongli ; Jiao, Cuicui ; Cao, Zengguo ; Huang, Pei ; Chi, Hang ; Bai, Yujie ; Liu, Di ; Wang, Jianzhong ; Feng, Na ; Li, Nan ; Zhao, Yongkun ; Wang, Tiecheng ; Gao, Yuwei ; Yang, Songtao ; Xia, Xianzhu ; Wang, Hualei</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c601t-be8699847cfd6e691d94ea1c765a3955706806f03edd3cd06bc5d3412cbe81d43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Adenoviruses</topic><topic>Adults</topic><topic>Antibodies</topic><topic>Biology and Life Sciences</topic><topic>CD4 antigen</topic><topic>CD8 antigen</topic><topic>Cell activation</topic><topic>Cell membranes</topic><topic>Cells</topic><topic>Cytokines</topic><topic>Disease control</topic><topic>Domains</topic><topic>E protein</topic><topic>Gene expression</topic><topic>Genetic 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Here, three kinds of recombinant rabies virus (RABV) encoding the prM-E protein of ZIKV were constructed: ZI-D (prM-E), ZI-E (transmembrane domain (TM) of prM-E replaced with RABV G) and ZI-F (signal peptide and TM domain of prM-E replaced with the region of RABV G). When the TM of prM-E was replaced with the region of RABV G (termed ZI-E), it promoted ZIKV E protein localization on the cell membrane and assembly on recombinant viruses. In addition, the change in the signal peptide with RABV G (termed ZI-F) was not conducive to foreign protein expression. The immunogenicity of recombinant viruses mixed with a complex adjuvant of ISA 201 VG and poly(I:C) was tested in BALB/c mice. After immunization with ZI-E, the anti-ZIKV IgG antibody lasted for at least 10 weeks. The titers of neutralizing antibodies (NAbs) against ZIKV and RABV at week 6 were all greater than the protective titers. Moreover, ZI-E stimulated the proliferation of splenic lymphocytes and promoted the secretion of cytokines. It also promoted the production of central memory T cells (TCMs) among CD4+/CD8+ T cells and stimulated B cell activation and maturation. These results indicate that ZI-E could induce ZIKV-specific humoral and cellular immune responses, which have the potential to be developed into a promising vaccine for protection against both ZIKV and RABV infections.</abstract><cop>San Francisco</cop><pub>Public Library of Science</pub><pmid>34086672</pmid><doi>10.1371/journal.pntd.0009484</doi><orcidid>https://orcid.org/0000-0001-6961-1991</orcidid><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 1935-2735 |
| ispartof | PLoS neglected tropical diseases, 2021-06, Vol.15 (6), p.e0009484-e0009484 |
| issn | 1935-2735 1935-2727 1935-2735 |
| language | eng |
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| source | DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; PubMed Central Open Access; Public Library of Science (PLoS) |
| subjects | Adenoviruses Adults Antibodies Biology and Life Sciences CD4 antigen CD8 antigen Cell activation Cell membranes Cells Cytokines Disease control Domains E protein Gene expression Genetic aspects Genetically modified organisms Health aspects IgG antibody Immune response (cell-mediated) Immune response (humoral) Immunity Immunization Immunogenicity Immunoglobulin G Immunological memory Immunological research Infections Laboratory animals Localization Lymphocytes Lymphocytes T Lyssavirus Medicine and Health Sciences Memory cells Microscopy Neonates Pandemics Pathogenesis Pathogens Poly (I:C) Polyclonal antibodies Polyinosinic:polycytidylic acid Prevention Proliferation Proteins Rabies Recombinants Research and Analysis Methods Respiratory diseases Secretion Spleen Tropical diseases Vaccines Vector-borne diseases Viral proteins Viral vaccines Viruses Zika virus |
| title | An inactivated recombinant rabies virus displaying the Zika virus prM-E induces protective immunity against both pathogens |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-12T19%3A15%3A15IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=An%20inactivated%20recombinant%20rabies%20virus%20displaying%20the%20Zika%20virus%20prM-E%20induces%20protective%20immunity%20against%20both%20pathogens&rft.jtitle=PLoS%20neglected%20tropical%20diseases&rft.au=Jin,%20Hongli&rft.date=2021-06-01&rft.volume=15&rft.issue=6&rft.spage=e0009484&rft.epage=e0009484&rft.pages=e0009484-e0009484&rft.issn=1935-2735&rft.eissn=1935-2735&rft_id=info:doi/10.1371/journal.pntd.0009484&rft_dat=%3Cgale_plos_%3EA668346733%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2552289300&rft_id=info:pmid/34086672&rft_galeid=A668346733&rft_doaj_id=oai_doaj_org_article_ba885491555e46738a09e5d5f956d0ae&rfr_iscdi=true |