{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T10:26:27Z","timestamp":1770459987715,"version":"3.49.0"},"update-to":[{"DOI":"10.1371\/journal.pntd.0009484","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,6,16]],"date-time":"2021-06-16T00:00:00Z","timestamp":1623801600000}}],"reference-count":47,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2021,6,4]],"date-time":"2021-06-04T00:00:00Z","timestamp":1622764800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"crossref","award":["2132020KJC016"],"award-info":[{"award-number":["2132020KJC016"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.1371\/journal.pntd.0009484","type":"journal-article","created":{"date-parts":[[2021,6,4]],"date-time":"2021-06-04T18:59:01Z","timestamp":1622833141000},"page":"e0009484","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":11,"title":["An inactivated recombinant rabies virus displaying the Zika virus prM-E induces protective immunity against both pathogens"],"prefix":"10.1371","volume":"15","author":[{"given":"Hongli","family":"Jin","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cuicui","family":"Jiao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zengguo","family":"Cao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pei","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hang","family":"Chi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yujie","family":"Bai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Di","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianzhong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Na","family":"Feng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nan","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongkun","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tiecheng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuwei","family":"Gao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Songtao","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xianzhu","family":"Xia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6961-1991","authenticated-orcid":true,"given":"Hualei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2021,6,4]]},"reference":[{"issue":"5","key":"pntd.0009484.ref001","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/0035-9203(52)90042-4","article-title":"Zika virus. I. Isolations and serological specificity","volume":"46","author":"GW Dick","year":"1952","journal-title":"Trans R Soc Trop Med Hyg"},{"key":"pntd.0009484.ref002","unstructured":"WHO. https:\/\/wwwwhoint\/emergencies\/diseases\/zika\/zika-epidemiology-update-july-2019pdf?ua=1."},{"issue":"3","key":"pntd.0009484.ref003","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1021\/acsinfecdis.6b00030","article-title":"Zika Virus: Diagnosis, Therapeutics, and Vaccine","volume":"2","author":"C Shan","year":"2016","journal-title":"ACS Infect Dis"},{"issue":"11","key":"pntd.0009484.ref004","doi-asserted-by":"crossref","DOI":"10.3390\/pathogens9110898","article-title":"Zika Virus","volume":"9","author":"S Masmejan","year":"2020","journal-title":"Pathogens"},{"key":"pntd.0009484.ref005","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.ebiom.2016.09.028","article-title":"Preventative Vaccines for Zika Virus Outbreak: Preliminary Evaluation","volume":"13","author":"E Kim","year":"2016","journal-title":"EBioMedicine"},{"issue":"6304","key":"pntd.0009484.ref006","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1126\/science.aah6157","article-title":"Protective efficacy of multiple vaccine platforms against Zika virus challenge in rhesus monkeys","volume":"353","author":"P Abbink","year":"2016","journal-title":"Science"},{"issue":"1","key":"pntd.0009484.ref007","doi-asserted-by":"crossref","first-page":"17385","DOI":"10.1038\/s41598-018-35724-6","article-title":"A Vaccine Based on a Modified Vaccinia Virus Ankara Vector Expressing Zika Virus Structural Proteins Controls Zika Virus Replication in Mice","volume":"8","author":"P Perez","year":"2018","journal-title":"Sci Rep"},{"issue":"1","key":"pntd.0009484.ref008","doi-asserted-by":"crossref","first-page":"3067","DOI":"10.1038\/s41467-018-05276-4","article-title":"A Zika virus vaccine expressing premembrane-envelope-NS1 polyprotein","volume":"9","author":"A Li","year":"2018","journal-title":"Nat Commun"},{"issue":"7614","key":"pntd.0009484.ref009","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1038\/nature18938","article-title":"Structural basis of potent Zika-dengue virus antibody cross-neutralization","volume":"536","author":"G Barba-Spaeth","year":"2016","journal-title":"Nature"},{"issue":"7606","key":"pntd.0009484.ref010","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1038\/nature18296","article-title":"The Brazilian Zika virus strain causes birth defects in experimental models","volume":"534","author":"FR Cugola","year":"2016","journal-title":"Nature"},{"issue":"1","key":"pntd.0009484.ref011","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1038\/s41467-018-02975-w","article-title":"Development of a chimeric Zika vaccine using a licensed live-attenuated flavivirus vaccine as backbone","volume":"9","author":"XF Li","year":"2018","journal-title":"Nat Commun"},{"key":"pntd.0009484.ref012","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/B978-0-12-387040-7.00009-3","article-title":"Rabies virus as a research tool and viral vaccine vector","volume":"79","author":"EA Gomme","year":"2011","journal-title":"Adv Virus Res"},{"issue":"1","key":"pntd.0009484.ref013","doi-asserted-by":"crossref","first-page":"4223","DOI":"10.1038\/s41467-018-06741-w","article-title":"Non-neutralizing antibodies elicited by recombinant Lassa-Rabies vaccine are critical for protection against Lassa fever","volume":"9","author":"T Abreu-Mota","year":"2018","journal-title":"Nat Commun"},{"issue":"8","key":"pntd.0009484.ref014","doi-asserted-by":"crossref","DOI":"10.1128\/JVI.02077-16","article-title":"Inactivated Recombinant Rabies Viruses Displaying Canine Distemper Virus Glycoproteins Induce Protective Immunity against Both Pathogens","volume":"91","author":"R da Fontoura Budaszewski","year":"2017","journal-title":"J Virol"},{"issue":"2","key":"pntd.0009484.ref015","doi-asserted-by":"crossref","DOI":"10.1128\/JVI.02040-16","article-title":"One-Health: a Safe, Efficient, Dual-Use Vaccine for Humans and Animals against Middle East Respiratory Syndrome Coronavirus and Rabies Virus","volume":"91","author":"C Wirblich","year":"2017","journal-title":"J Virol"},{"issue":"Suppl 2","key":"pntd.0009484.ref016","doi-asserted-by":"crossref","first-page":"S414","DOI":"10.1093\/infdis\/jiv251","article-title":"Preclinical Development of Inactivated Rabies Virus-Based Polyvalent Vaccine Against Rabies and Filoviruses","volume":"212","author":"M Willet","year":"2015","journal-title":"J Infect Dis"},{"issue":"1","key":"pntd.0009484.ref017","doi-asserted-by":"crossref","first-page":"7679","DOI":"10.1038\/s41598-017-08247-9","article-title":"Virus-like particles that display Zika virus envelope protein domain III induce potent neutralizing immune responses in mice.","volume":"7","author":"M Yang","year":"2017","journal-title":"Sci Rep"},{"issue":"6309","key":"pntd.0009484.ref018","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1126\/science.aai9137","article-title":"Rapid development of a DNA vaccine for Zika virus","volume":"354","author":"KA Dowd","year":"2016","journal-title":"Science"},{"issue":"2","key":"pntd.0009484.ref019","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.immuni.2017.02.005","article-title":"Prospects for a Zika Virus Vaccine","volume":"46","author":"DH Barouch","year":"2017","journal-title":"Immunity"},{"issue":"7617","key":"pntd.0009484.ref020","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1038\/nature18952","article-title":"Vaccine protection against Zika virus from Brazil","volume":"536","author":"RA Larocca","year":"2016","journal-title":"Nature"},{"issue":"11","key":"pntd.0009484.ref021","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1016\/j.tibtech.2019.03.013","article-title":"Production and Biomedical Application of Flavivirus-like Particles","volume":"37","author":"E Krol","year":"2019","journal-title":"Trends Biotechnol"},{"issue":"2","key":"pntd.0009484.ref022","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1007\/s11262-014-1160-y","article-title":"Using rabies virus vaccine strain SRV9 as viral vector to express exogenous gene","volume":"50","author":"H Wang","year":"2015","journal-title":"Virus Genes"},{"issue":"20","key":"pntd.0009484.ref023","doi-asserted-by":"crossref","first-page":"10605","DOI":"10.1128\/JVI.00558-11","article-title":"Inactivated or live-attenuated bivalent vaccines that confer protection against rabies and Ebola viruses","volume":"85","author":"JE Blaney","year":"2011","journal-title":"J Virol"},{"issue":"1","key":"pntd.0009484.ref024","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1186\/s13073-018-0561-2","article-title":"Developing Zika vaccines: the lessons for disease X","volume":"10","author":"ADT Barrett","year":"2018","journal-title":"Genome Med"},{"issue":"5","key":"pntd.0009484.ref025","doi-asserted-by":"crossref","first-page":"e0005608","DOI":"10.1371\/journal.pntd.0005608","article-title":"Zika virus-like particle (VLP) based vaccine","volume":"11","author":"H Boigard","year":"2017","journal-title":"PLoS Negl Trop Dis"},{"issue":"10","key":"pntd.0009484.ref026","doi-asserted-by":"crossref","DOI":"10.3390\/v11100919","article-title":"Genetically Modified Rabies Virus Vector-Based Rift Valley Fever Virus Vaccine is Safe and Induces Efficacious Immune Responses in Mice","volume":"11","author":"S Zhang","year":"2019","journal-title":"Viruses"},{"issue":"1","key":"pntd.0009484.ref027","article-title":"Characterization of the Immune Response of MERS-CoV Vaccine Candidates Derived from Two Different Vectors in Mice","volume":"12","author":"E Li","year":"2020","journal-title":"Viruses"},{"issue":"9","key":"pntd.0009484.ref028","volume":"11","author":"E Li","year":"2019","journal-title":"A Novel Bacterium-Like Particle Vaccine Displaying the MERS-CoV Receptor-Binding Domain Induces Specific Mucosal and Systemic Immune Responses in Mice. Viruses"},{"issue":"6","key":"pntd.0009484.ref029","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.1016\/j.celrep.2016.07.049","article-title":"Broadly Neutralizing Activity of Zika Virus-Immune Sera Identifies a Single Viral Serotype","volume":"16","author":"KA Dowd","year":"2016","journal-title":"Cell Rep"},{"issue":"1","key":"pntd.0009484.ref030","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1128\/JVI.02308-14","article-title":"Rhabdovirus-based vaccine platforms against henipaviruses","volume":"89","author":"D Kurup","year":"2015","journal-title":"J Virol"},{"key":"pntd.0009484.ref031","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1038\/s41541-020-00248-6","article-title":"Rabies virus-based COVID-19 vaccine CORAVAX induces high levels of neutralizing antibodies against SARS-CoV-2","volume":"5","author":"D Kurup","year":"2020","journal-title":"NPJ Vaccines"},{"issue":"12","key":"pntd.0009484.ref032","article-title":"A Novel Bacterium-Like Particle-Based Vaccine Displaying the SUDV Glycoprotein Induces Potent Humoral and Cellular Immune Responses in Mice","volume":"11","author":"S Xu","year":"2019","journal-title":"Viruses"},{"issue":"5","key":"pntd.0009484.ref033","doi-asserted-by":"crossref","first-page":"e1003389","DOI":"10.1371\/journal.ppat.1003389","article-title":"Antibody quality and protection from lethal Ebola virus challenge in nonhuman primates immunized with rabies virus based bivalent vaccine","volume":"9","author":"JE Blaney","year":"2013","journal-title":"PLoS Pathog"},{"issue":"3","key":"pntd.0009484.ref034","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1016\/j.cell.2016.09.020","article-title":"Zika Virus: Immunity and Vaccine Development","volume":"167","author":"TC Pierson","year":"2016","journal-title":"Cell"},{"issue":"1","key":"pntd.0009484.ref035","doi-asserted-by":"crossref","first-page":"2441","DOI":"10.1038\/s41467-018-04859-5","article-title":"Rational Zika vaccine design via the modulation of antigen membrane anchors in chimpanzee adenoviral vectors","volume":"9","author":"C Lopez-Camacho","year":"2018","journal-title":"Nat Commun"},{"issue":"1","key":"pntd.0009484.ref036","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.jviromet.2009.05.018","article-title":"Development and evaluation of a rapid neutralizing antibody test for rabies","volume":"161","author":"S Shiota","year":"2009","journal-title":"J Virol Methods"},{"key":"pntd.0009484.ref037","first-page":"1","volume":"931","author":"WHO Expert Consultation on rabies","year":"2005","journal-title":"World Health Organ Tech Rep Ser"},{"key":"pntd.0009484.ref038","doi-asserted-by":"crossref","first-page":"197638","DOI":"10.1016\/j.virusres.2019.06.001","article-title":"Adjuvant activity of PCP-II, a polysaccharide from Poria cocos, on a whole killed rabies vaccine","volume":"270","author":"W Zhang","year":"2019","journal-title":"Virus Res"},{"issue":"10","key":"pntd.0009484.ref039","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1097\/PEC.0b013e3182a63125","article-title":"Revised 4-dose vaccine schedule as part of postexposure prophylaxis to prevent human rabies","volume":"29","author":"MK Mittal","year":"2013","journal-title":"Pediatr Emerg Care"},{"issue":"1","key":"pntd.0009484.ref040","doi-asserted-by":"crossref","first-page":"14769","DOI":"10.1038\/s41598-017-15039-8","article-title":"A Zika Vaccine Targeting NS1 Protein Protects Immunocompetent Adult Mice in a Lethal Challenge Model","volume":"7","author":"AC Brault","year":"2017","journal-title":"Sci Rep"},{"issue":"6","key":"pntd.0009484.ref041","doi-asserted-by":"crossref","first-page":"1589","DOI":"10.1016\/j.theriogenology.2016.05.019","article-title":"Effectiveness of an immunocastration vaccine formulation to reduce the gonadal function in female and male mice by Th1\/Th2 immune response","volume":"86","author":"D Siel","year":"2016","journal-title":"Theriogenology"},{"key":"pntd.0009484.ref042","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1034\/j.1600-065X.2000.00607.x","article-title":"B-cell activation by T-cell-independent type 2 antigens as an integral part of the humoral immune response to pathogenic microorganisms","volume":"176","author":"Q Vos","year":"2000","journal-title":"Immunol Rev"},{"issue":"6824","key":"pntd.0009484.ref043","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1038\/35065118","article-title":"Skewed maturation of memory HIV-specific CD8 T lymphocytes","volume":"410","author":"P Champagne","year":"2001","journal-title":"Nature"},{"issue":"4","key":"pntd.0009484.ref044","doi-asserted-by":"crossref","first-page":"e0122571","DOI":"10.1371\/journal.pone.0122571","article-title":"Characterization of effector and memory T cell subsets in the immune response to bovine tuberculosis in cattle","volume":"10","author":"MF Maggioli","year":"2015","journal-title":"PLoS One"},{"issue":"11","key":"pntd.0009484.ref045","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1016\/S1473-3099(16)30270-5","article-title":"Potential for Zika virus introduction and transmission in resource-limited countries in Africa and the Asia-Pacific region: a modelling study","volume":"16","author":"II Bogoch","year":"2016","journal-title":"Lancet Infect Dis"},{"issue":"5","key":"pntd.0009484.ref046","first-page":"360","article-title":"Re-evaluating the burden of rabies in Africa and Asia","volume":"83","author":"DL Knobel","year":"2005","journal-title":"Bull World Health Organ"},{"issue":"1","key":"pntd.0009484.ref047","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1111\/jsap.12934","article-title":"Development of non-governmental organisation-academic partnership to tackle rabies in Africa and Asia","volume":"60","author":"L Gamble","year":"2019","journal-title":"J Small Anim Pract"}],"updated-by":[{"DOI":"10.1371\/journal.pntd.0009484","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,6,16]],"date-time":"2021-06-16T00:00:00Z","timestamp":1623801600000}}],"container-title":["PLOS Neglected Tropical Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0009484","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,6,16]],"date-time":"2021-06-16T17:34:14Z","timestamp":1623864854000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0009484"}},"subtitle":[],"editor":[{"given":"Ana M.","family":"Moura-da-Silva","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2021,6,4]]},"references-count":47,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2021,6,4]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pntd.0009484","relation":{"new_version":[{"id-type":"doi","id":"10.1371\/journal.pntd.0009484","asserted-by":"object"}]},"ISSN":["1935-2735"],"issn-type":[{"value":"1935-2735","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,4]]}}}