{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T15:55:11Z","timestamp":1782402911236,"version":"3.54.5"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,6,8]],"date-time":"2022-06-08T00:00:00Z","timestamp":1654646400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p>Rabies is a highly prevalent zoonotic disease and a public health threat worldwide. Currently licensed rabies vaccines are effective but less is known which would protect cattle. This study describes the construction of a novel recombinant bovine herpes virus type I (BHV-1) expressing rabies virus glycoprotein (RABV G) instead of its gE glycoprotein (gE) by CRISPR-Cas9 and homologous recombination technology (BHV-1-\u0394gE-G). Insertion of the RABV G gene is stable after 20 rounds of<jats:italic>in vitro<\/jats:italic>passaging and the recombinant virus replicates to high titers in MDBK cells. The RABV G expresses in the recombinant virus-infected cells and on the virion surface of BHV-1-\u0394gE-G. One single immunization with BHV-1-\u0394gE-G-activated dendritic cells (DCs) and B cells furthermore induced a protective immune response in mice against severe lethal challenge infection. A protective level of RABV-specific virus-neutralizing antibody (VNA) was detected in intramuscular immunized mice and cattle without any clinical symptoms. This research demonstrated that the BHV-1 vector-based RABV vaccine is a potential candidate for cattle.<\/jats:p>","DOI":"10.3389\/fmicb.2022.931043","type":"journal-article","created":{"date-parts":[[2022,6,8]],"date-time":"2022-06-08T07:00:13Z","timestamp":1654671613000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["A Novel Rabies Vaccine Based on a Recombinant Bovine Herpes Virus Type 1 Expressing Rabies Virus Glycoprotein"],"prefix":"10.3389","volume":"13","author":[{"given":"Caiquan","family":"Zhao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongzhi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina","family":"Ji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Qin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,6,8]]},"reference":[{"key":"B1","article-title":"Bovine herpesvirus mutant type 5, vaccine directed against bovine viral encephalitis (bhv-5) and the rabies virus and vaccine preparation method.","volume-title":"Google Patents","author":"Ana","year":"2002"},{"key":"B2","doi-asserted-by":"publisher","first-page":"e00525","DOI":"10.1128\/JVI.00525-17","article-title":"Use of a recombinant gamma-2 herpesvirus vaccine vector against dengue virus in rhesus monkeys","volume":"91","author":"Bischof","year":"2017","journal-title":"J. Virol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1016\/j.copbio.2005.07.002","article-title":"Replication-defective genomic HSV gene therapy vectors: design, production and CNS applications","volume":"7","author":"Burton","year":"2005","journal-title":"Curr. Opin. Mol. Ther."},{"key":"B4","doi-asserted-by":"publisher","first-page":"2224","DOI":"10.1016\/j.vaccine.2019.03.008","article-title":"Feline herpesvirus vectored-rabies vaccine in cats: a dual protection","volume":"37","author":"Chen","year":"2019","journal-title":"Vaccine"},{"key":"B5","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/j.jbiotec.2014.04.006","article-title":"The preparation of porcine circovirus type 2 (PCV2) virus-like particles using a recombinant pseudorabies virus and its application to vaccine development","volume":"181","author":"Chi","year":"2014","journal-title":"J. Biotechnol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"46","DOI":"10.3390\/vaccines9010046","article-title":"BoHV-1-Vectored BVDV-2 subunit vaccine induces BVDV cross-reactive cellular immune responses and protects against BVDV-2 challenge","volume":"9","author":"Chowdhury","year":"2021","journal-title":"Vaccines"},{"key":"B7","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/S0022-1759(97)00212-3","article-title":"Development of a fluorescent antibody virus neutralisation test (FAVN test) for the quantitation of rabies-neutralising antibody","volume":"212","author":"Cliquet","year":"1998","journal-title":"J. Immunol. Methods"},{"key":"B8","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1126\/science.1231143","article-title":"Multiplex genome engineering using CRISPR\/Cas systems","volume":"339","author":"Cong","year":"2013","journal-title":"Science"},{"key":"B9","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1016\/j.jviromet.2009.09.016","article-title":"The combination of marker gene swapping and fluorescence-activated cell sorting improves the efficiency of recombinant modified vaccinia virus Ankara vaccine production for human use","volume":"163","author":"Di Lullo","year":"2010","journal-title":"J. Virol. Methods"},{"key":"B10","doi-asserted-by":"publisher","first-page":"4888","DOI":"10.1016\/j.vaccine.2013.07.034","article-title":"Immunogenicity of a reduced-dose whole killed rabies vaccine is significantly enhanced by ISCOMATRIX adjuvant, Merck amorphous aluminum hydroxylphosphate sulfate (MAA) or a synthetic TLR9 agonist in rhesus macaques","volume":"31","author":"DiStefano","year":"2013","journal-title":"Vaccine"},{"key":"B11","doi-asserted-by":"publisher","first-page":"2825","DOI":"10.3201\/eid2612.200303","article-title":"Animal rabies surveillance, China, 2004-2018","volume":"26","author":"Feng","year":"2020","journal-title":"Emerg. Infect. Dis."},{"key":"B12","doi-asserted-by":"publisher","first-page":"20120142","DOI":"10.1098\/rstb.2012.0142","article-title":"The elimination of fox rabies from Europe: determinants of success and lessons for the future","volume":"368","author":"Freuling","year":"2013","journal-title":"Philos. Trans. R. Soc. Lond. B. Biol. Sci."},{"key":"B13","doi-asserted-by":"publisher","first-page":"397","DOI":"10.7589\/2013-07-183","article-title":"Vaccine-induced rabies in a red fox (Vulpes vulpes): isolation of vaccine virus in brain tissue and salivary glands","volume":"50","author":"Hostnik","year":"2014","journal-title":"J. Wildl. Dis."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1187","DOI":"10.1007\/s00705-010-0709-x","article-title":"Characterization of conformation-specific monoclonal antibodies against rabies virus nucleoprotein","volume":"155","author":"Jiang","year":"2010","journal-title":"Arch. Virol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1016\/0264-410X(94)90122-8","article-title":"A conventionally attenuated glycoprotein E-negative strain of bovine herpesvirus type 1 is an efficacious and safe vaccine","volume":"12","author":"Kaashoek","year":"1994","journal-title":"Vaccine"},{"key":"B16","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1016\/j.virol.2006.08.007","article-title":"Ability of herpes simplex virus vectors to boost immune responses to DNA vectors and to protect against challenge by simian immunodeficiency virus","volume":"357","author":"Kaur","year":"2007","journal-title":"Virology"},{"key":"B17","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1292\/jvms.61.395","article-title":"Bovine herpes virus expressing envelope protein (E2) of bovine viral diarrhea virus as a vaccine candidate","volume":"61","author":"Kweon","year":"1999","journal-title":"J. Vet. Med. Sci."},{"key":"B18","doi-asserted-by":"publisher","first-page":"632957","DOI":"10.3389\/fcell.2020.632957","article-title":"Change in the single amino acid site 83 in rabies virus glycoprotein enhances the BBB permeability and reduces viral pathogenicity","volume":"8","author":"Li","year":"2020","journal-title":"Front. Cell Dev. Biol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"218","DOI":"10.3390\/v11030218","article-title":"Deficient incorporation of rabies virus glycoprotein into virions enhances virus-induced immune evasion and viral pathogenicity","volume":"11","author":"Li","year":"2019","journal-title":"Viruses"},{"key":"B20","doi-asserted-by":"publisher","first-page":"e02324","DOI":"10.1128\/JVI.02324-16","article-title":"Overexpressin of Interleukin-7 extends the humoral immune response induced by rabies vaccination","volume":"91","author":"Li","year":"2017","journal-title":"J. Virol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"e0004890","DOI":"10.1371\/journal.pntd.0004890","article-title":"Rabies outbreaks and vaccination in domestic camels and cattle in Northwest China","volume":"10","author":"Liu","year":"2016","journal-title":"PLoS Negl. Trop. Dis."},{"key":"B22","doi-asserted-by":"publisher","first-page":"421","DOI":"10.3389\/fimmu.2018.00421","article-title":"Bovine Herpesvirus-4-Based vector delivering peste des petits ruminants virus hemagglutinin ORF Induces both neutralizing antibodies and cytotoxic T cell responses","volume":"9","author":"Macchi","year":"2018","journal-title":"Front. Immunol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"510","DOI":"10.1128\/JVI.73.1.510-518.1999","article-title":"Pathogenicity of different rabies virus variants inversely correlates with apoptosis and rabies virus glycoprotein expression in infected primary neuron cultures","volume":"73","author":"Morimoto","year":"1999","journal-title":"J. Virol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"2003","DOI":"10.3969\/j.issn.1674-7968.2018.12.001","article-title":"Construction of BHV-1 gE deletion strain based on CRISPR\/Cas9 technique and preliminary identification of its immunobiological characteristics","volume":"26","author":"Mu","year":"2018","journal-title":"J. Agric. Biotechnol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"115","DOI":"10.3390\/vaccines8010115","article-title":"Bovine Herpesvirus-4-Vectored delivery of nipah virus glycoproteins enhances T cell immunogenicity in pigs","volume":"8","author":"Pedrera","year":"2020","journal-title":"Vaccines"},{"key":"B26","doi-asserted-by":"publisher","first-page":"23","DOI":"10.3390\/v11010023","article-title":"Antibody responses to Bovine Alphaherpesvirus 1 (BoHV-1) in passively immunized calves","volume":"11","author":"Petrini","year":"2019","journal-title":"Viruses"},{"key":"B27","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1080\/03079450500059032","article-title":"Recombinant rabies virus vaccine strain SAD-l16 inoculated intracerebrally in young mice produces a severe encephalitis with extensive neuronal apoptosis","volume":"69","author":"Rasalingam","year":"2005","journal-title":"Can. J. Vet. Res."},{"key":"B28","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1016\/S0952-7915(00)00148-5","article-title":"Building better vaccines: how apoptotic cell death can induce inflammation and activate innate and adaptive immunity","volume":"12","author":"Restifo","year":"2000","journal-title":"Curr. Opin. Immunol."},{"key":"B29","doi-asserted-by":"crossref","first-page":"4467","DOI":"10.4049\/jimmunol.161.9.4467","article-title":"Bystander apoptosis triggers dendritic cell maturation and antigen-presenting function","volume":"161","author":"Rovere","year":"1998","journal-title":"J. Immunol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"3307","DOI":"10.1128\/JVI.72.4.3307-3320.1998","article-title":"Persistence and expression of the herpes simplex virus genome in the absence of immediate-early proteins","volume":"72","author":"Samaniego","year":"1998","journal-title":"J. Virol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1080\/13550280500385310","article-title":"Glycoprotein-mediated induction of apoptosis limits the spread of attenuated rabies viruses in the central nervous system of mice","volume":"11","author":"Sarmento","year":"2005","journal-title":"J. Neurovirol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"1908","DOI":"10.1016\/S0264-410X(97)00129-1","article-title":"Immunization of cattle with a BHV1 vector vaccine or a DNA vaccine both coding for the G protein of BRSV","volume":"15","author":"Schrijver","year":"1997","journal-title":"Vaccine"},{"key":"B33","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1017\/S0950268810001263","article-title":"Genetic evidence for domestic raccoon dog rabies caused by Arctic-like rabies virus in Inner Mongolia, China","volume":"139","author":"Shao","year":"2011","journal-title":"Epidemiol. Infect."},{"key":"B34","doi-asserted-by":"publisher","first-page":"374286","DOI":"10.4061\/2011\/374286","article-title":"Role of apoptosis in rabies viral encephalitis: a comparative study in mice, canine, and human brain with a review of literature","volume":"2011","author":"Suja","year":"2011","journal-title":"Patholog. Res. Int."},{"key":"B35","doi-asserted-by":"publisher","first-page":"5021","DOI":"10.1016\/j.vaccine.2016.08.013","article-title":"Vaccine-induced rabies case in a cow (Bos taurus): molecular characterisation of vaccine strain in brain tissue","volume":"34","author":"Vuta","year":"2016","journal-title":"Vaccine"},{"key":"B36","doi-asserted-by":"publisher","first-page":"1634","DOI":"10.1128\/JVI.01552-10","article-title":"Rabies virus expressing dendritic cell-activating molecules enhances the innate and adaptive immune response to vaccination","volume":"85","author":"Wen","year":"2011","journal-title":"J. Virol."},{"key":"B37","first-page":"1","volume":"982","year":"2013","journal-title":"WHO Expert Consultation on Rabies"},{"key":"B38","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1016\/j.prevetmed.2015.05.004","article-title":"Cattle rabies vaccination\u2013A longitudinal study of rabies antibody titres in an Israeli dairy herd","volume":"121","author":"Yakobson","year":"2015","journal-title":"Prev. Vet. Med."},{"key":"B39","doi-asserted-by":"publisher","first-page":"2157","DOI":"10.1128\/JVI.02092-14","article-title":"The inability of wild-type rabies virus to activate dendritic cells is dependent on the glycoprotein and correlates with its low level of the de novo-synthesized leader RNA","volume":"89","author":"Yang","year":"2015","journal-title":"J. Virol."},{"key":"B40","doi-asserted-by":"publisher","first-page":"662","DOI":"10.1016\/j.ymthe.2006.03.027","article-title":"A chimpanzee-origin adenovirus vector expressing the rabies virus glycoprotein as an oral vaccine against inhalation infection with rabies virus","volume":"14","author":"Zhou","year":"2006","journal-title":"Mol. Ther."}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2022.931043\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,7]],"date-time":"2023-02-07T17:39:05Z","timestamp":1675791545000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2022.931043\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,8]]},"references-count":40,"alternative-id":["10.3389\/fmicb.2022.931043"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2022.931043","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,8]]},"article-number":"931043"}}