{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T18:10:13Z","timestamp":1756231813657,"version":"3.44.0"},"reference-count":45,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T00:00:00Z","timestamp":1756166400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100021171","name":"Basic and Applied Basic Research Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2022A1515110673"],"award-info":[{"award-number":["2022A1515110673"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2022A1515012511"],"award-info":[{"award-number":["2022A1515012511"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82002696"],"award-info":[{"award-number":["82002696"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:p>Rabies, caused by the rabies virus (RABV), remains a global public health issue. Traditional inactivated rabies vaccines are costly, risky, and require multiple doses for post-exposure prophylaxis. The rabies virus glycoprotein (RABV-G), essential for inducing protective antibodies, is crucial for new vaccine development. Lentiviral vectors offer promise due to their efficient gene delivery and strong immune responses. We designed three recombinant pseudotyped lentiviral vector vaccines with enhanced green fluorescent protein (eGFP) as marker, among VSV-G\/LV-RABV-G the RABV-G only lies in the core of pseudotyped lentiviral particle, among RABV-G\/LV-RABV-G the RABV-G lies in both of the core and the envelop and among RABV-G\/LV-eGFP the RABV-G only lies in the envelop. These were tested for antigenicity, infectivity, and neutralizing antibody response. All vaccines showed strong antigen specificity and high titers for virus particles production. Immunization tests in mice showed that VSV-G\/LV-RABV-G and RABV-G\/LV-RABV-G vaccines induced high neutralizing antibody levels within 3 days, sustained up to 10 weeks. The RABV-G\/LV-eGFP vaccine, especially with CPG-ODN adjuvant, also generated significant antibody responses. In summary, the recombinant pseudotyped lentiviral vector vaccines based on the RABV-G show promise for effective, single-dose rabies vaccination.<\/jats:p>","DOI":"10.1371\/journal.pntd.0013404","type":"journal-article","created":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T17:45:07Z","timestamp":1756230307000},"page":"e0013404","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Novel rabies vaccine candidates development based on pseudotyped lentiviral vectors with rabies virus glycoprotein"],"prefix":"10.1371","volume":"19","author":[{"given":"Lifang","family":"Shuai","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingyu","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nana","family":"Pei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheng","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marwa","family":"Belghait","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiming","family":"Hu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinlong","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongwei","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yingying","family":"Mao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4392-0849","authenticated-orcid":true,"given":"Hongyan","family":"Du","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2025,8,26]]},"reference":[{"key":"pntd.0013404.ref001","doi-asserted-by":"crossref","first-page":"101992","DOI":"10.1016\/j.cimid.2023.101992","article-title":"Canine rabies: an epidemiological significance, pathogenesis, diagnosis, prevention, and public health issues","volume":"97","author":"A Kumar","year":"2023","journal-title":"Comp Immunol Microbiol Infect Dis"},{"issue":"4","key":"pntd.0013404.ref002","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1001\/jama.2022.22254","article-title":"Rabies","volume":"329","author":"J Jin","year":"2023","journal-title":"JAMA"},{"issue":"5","key":"pntd.0013404.ref003","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":"2","key":"pntd.0013404.ref004","doi-asserted-by":"crossref","first-page":"657","DOI":"10.20506\/rst.37.2.2831","article-title":"New developments in rabies vaccination","volume":"37","author":"CR Fisher","year":"2018","journal-title":"Rev Sci Tech"},{"issue":"1","key":"pntd.0013404.ref005","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1186\/s12985-022-01919-7","article-title":"An mRNA-based rabies vaccine induces strong protective immune responses in mice and dogs","volume":"19","author":"J Li","year":"2022","journal-title":"Virol J"},{"issue":"9","key":"pntd.0013404.ref006","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1016\/j.chom.2022.07.014","article-title":"Structure of trimeric pre-fusion rabies virus glycoprotein in complex with two protective antibodies","volume":"30","author":"WM Ng","year":"2022","journal-title":"Cell Host Microbe"},{"issue":"2","key":"pntd.0013404.ref007","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1007\/s00705-016-3128-9","article-title":"Rabies vaccine development by expression of recombinant viral glycoprotein","volume":"162","author":"RM Astray","year":"2016","journal-title":"Arch Virol"},{"issue":"3","key":"pntd.0013404.ref008","doi-asserted-by":"crossref","first-page":"189","DOI":"10.3390\/genes10030189","article-title":"RNA viruses as tools in gene therapy and vaccine development","volume":"10","author":"K Lundstrom","year":"2019","journal-title":"Genes (Basel)"},{"key":"pntd.0013404.ref009","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.coviro.2016.03.001","article-title":"Engineering virus-like particles as vaccine platforms","volume":"18","author":"KM Frietze","year":"2016","journal-title":"Curr Opin Virol"},{"issue":"12","key":"pntd.0013404.ref010","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.1080\/14760584.2021.1988854","article-title":"Use of lentiviral vectors in vaccination","volume":"20","author":"M-W Ku","year":"2021","journal-title":"Expert Rev Vaccines"},{"key":"pntd.0013404.ref011","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.omtm.2021.09.011","article-title":"Safety and efficiency modifications of SIV-based integrase-defective lentiviral vectors for immunization","volume":"23","author":"R Bona","year":"2021","journal-title":"Mol Ther Methods Clin Dev"},{"key":"pntd.0013404.ref012","doi-asserted-by":"crossref","first-page":"3443","DOI":"10.1016\/j.vaccine.2009.01.055","article-title":"Lentiviral vectors for HIV disease prevention and treatment","volume":"27","author":"F Lemiale","year":"2009","journal-title":"Vaccine"},{"key":"pntd.0013404.ref013","first-page":"243","article-title":"Recent advances in lentiviral vaccines for HIV-1 infection","volume":"7","author":"TD Norton","year":"2016","journal-title":"Front Immunol"},{"key":"pntd.0013404.ref014","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2018.00171","article-title":"Integrase defective lentiviral vector as a vaccine platform for delivering influenza antigens","volume":"9","author":"A Gallinaro","year":"2018","journal-title":"Front Immunol"},{"key":"pntd.0013404.ref015","article-title":"Intranasal lentiviral vector-mediated antibody delivery confers reduction of SARS-CoV-2 infection in elderly and immunocompromised mice","volume":"13","author":"Y Du","year":"2022","journal-title":"Front Immunol"},{"issue":"3","key":"pntd.0013404.ref016","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1002\/jgm.837","article-title":"A single immunization with a minute dose of a lentiviral vector-based vaccine is highly effective at eliciting protective humoral immunity against West Nile virus","volume":"8","author":"MC Iglesias","year":"2006","journal-title":"J Gene Med"},{"issue":"5","key":"pntd.0013404.ref017","doi-asserted-by":"crossref","first-page":"407","DOI":"10.7150\/ijms.11270","article-title":"Lentiviral vectors mediate long-term and high efficiency transgene expression in HEK 293T cells","volume":"12","author":"Y Mao","year":"2015","journal-title":"Int J Med Sci"},{"issue":"10","key":"pntd.0013404.ref018","doi-asserted-by":"crossref","first-page":"1282","DOI":"10.7150\/ijms.87134","article-title":"Immunogenicity and antigenicity of the ectodomain of rabies virus glycoprotein stably expressed in HEK293T cells","volume":"20","author":"Q Li","year":"2023","journal-title":"Int J Med Sci"},{"key":"pntd.0013404.ref019","first-page":"99","article-title":"Comparative studies of two potency tests for antirabies serum: neutralization test in mice (MNT) and rapid fluorescent focus inhibition test (RFFIT)","volume":"64","author":"J Kurz","year":"1986","journal-title":"Dev Biol Stand"},{"key":"pntd.0013404.ref020","doi-asserted-by":"crossref","first-page":"140275","DOI":"10.1016\/j.ijbiomac.2025.140275","article-title":"Development of a blocking ELISA for evaluating neutralizing antibodies in human and canine serum based on rabies virus glycoprotein epitope I","volume":"301","author":"H Mo","year":"2025","journal-title":"Int J Biol Macromol"},{"key":"pntd.0013404.ref021","doi-asserted-by":"crossref","first-page":"114769","DOI":"10.1016\/j.jviromet.2023.114769","article-title":"A simplified method for measuring neutralising antibodies against rabies virus","volume":"319","author":"G Wu","year":"2023","journal-title":"J Virol Methods"},{"issue":"4","key":"pntd.0013404.ref022","article-title":"Generation of a recombinant rabies virus expressing green fluorescent protein for a virus neutralization antibody assay","volume":"22","author":"DK Yang","year":"2021","journal-title":"J Vet Sci"},{"issue":"3","key":"pntd.0013404.ref023","doi-asserted-by":"crossref","first-page":"846","DOI":"10.3390\/pharmaceutics15030846","article-title":"Lentiviral vectors as a vaccine platform against infectious diseases","volume":"15","author":"K Nemirov","year":"2023","journal-title":"Pharmaceutics"},{"issue":"12","key":"pntd.0013404.ref024","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.1080\/14760584.2021.1988854","article-title":"Use of lentiviral vectors in vaccination","volume":"20","author":"M-W Ku","year":"2021","journal-title":"Expert Rev Vaccines"},{"key":"pntd.0013404.ref025","doi-asserted-by":"crossref","first-page":"132798","DOI":"10.1016\/j.ijbiomac.2024.132798","article-title":"Rapid production of COVID-19 subunit vaccine candidates and their immunogenicity evaluation in pigs","volume":"272","author":"R Yan","year":"2024","journal-title":"Inter J Biol Macromol"},{"key":"pntd.0013404.ref026","doi-asserted-by":"crossref","first-page":"661379","DOI":"10.3389\/fimmu.2021.661379","article-title":"Development of lentiviral vectors pseudotyped with influenza B hemagglutinins: application in vaccine immunogenicity, mAb potency, and sero-surveillance studies","volume":"12","author":"F Ferrara","year":"2021","journal-title":"Front Immunol"},{"key":"pntd.0013404.ref027","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1007\/978-981-99-0113-5_15","article-title":"Pseudotyped viruses for mammarenavirus","volume":"1407","author":"Q Li","year":"2023","journal-title":"Adv Exp Med Biol"},{"issue":"1","key":"pntd.0013404.ref028","doi-asserted-by":"crossref","first-page":"47","DOI":"10.2174\/1566523216666160119093948","article-title":"Pseudotyping viral vectors with emerging virus envelope proteins","volume":"16","author":"I Steffen","year":"2016","journal-title":"Curr Gene Ther"},{"key":"pntd.0013404.ref029","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.virusres.2019.02.006","article-title":"Early events in rabies virus infection-attachment, entry, and intracellular trafficking","volume":"263","author":"Y Guo","year":"2019","journal-title":"Virus Res"},{"key":"pntd.0013404.ref030","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.jim.2019.03.008","article-title":"Development and characterization of a Zaire Ebola (ZEBOV) specific IgM ELISA","volume":"468","author":"T Atre","year":"2019","journal-title":"J Immunol Methods"},{"issue":"12","key":"pntd.0013404.ref031","doi-asserted-by":"crossref","first-page":"1853","DOI":"10.1084\/jem.20031223","article-title":"A critical role for induced IgM in the protection against West Nile virus infection","volume":"198","author":"MS Diamond","year":"2003","journal-title":"J Exp Med"},{"issue":"4","key":"pntd.0013404.ref032","doi-asserted-by":"crossref","DOI":"10.1016\/S1473-3099(17)30574-1","article-title":"Comparative pathogenesis of rabies in bats and carnivores, and implications for spillover to humans","volume":"18","author":"L Begeman","year":"2018","journal-title":"Lancet Infect Dis"},{"issue":"6","key":"pntd.0013404.ref033","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1016\/j.ttbdis.2018.06.010","article-title":"Development of a serodiagnostic IgM-ELISA for tick-borne encephalitis virus using subviral particles with strep-tag","volume":"9","author":"M Nakayasu","year":"2018","journal-title":"Ticks Tick Borne Dis"},{"issue":"3","key":"pntd.0013404.ref034","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1099\/0022-1317-40-3-595","article-title":"Immunoglobulin (IgG) and (IgM) antibody responses to rabies vaccine","volume":"40","author":"GS Turner","year":"1978","journal-title":"J Gen Virol"},{"issue":"16","key":"pntd.0013404.ref035","doi-asserted-by":"crossref","first-page":"9217","DOI":"10.1128\/JVI.00995-13","article-title":"Reinvestigating the role of IgM in rabies virus postexposure vaccination","volume":"87","author":"CL Dorfmeier","year":"2013","journal-title":"J Virol"},{"issue":"1","key":"pntd.0013404.ref036","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1038\/s41392-023-01557-7","article-title":"Vaccine adjuvants: mechanisms and platforms","volume":"8","author":"T Zhao","year":"2023","journal-title":"Signal Transduct Target Ther"},{"key":"pntd.0013404.ref037","doi-asserted-by":"crossref","first-page":"1043109","DOI":"10.3389\/fimmu.2023.1043109","article-title":"New-age vaccine adjuvants, their development, and future perspective","volume":"14","author":"SK Verma","year":"2023","journal-title":"Front Immunol"},{"issue":"3","key":"pntd.0013404.ref038","doi-asserted-by":"crossref","first-page":"137","DOI":"10.2165\/00126839-200809030-00001","article-title":"A review of the role of CpG Oligodeoxynucleotides as toll-like receptor 9 agonists in prophylactic and therapeutic vaccine development in infectious diseases","volume":"9","author":"K Gupta","year":"2008","journal-title":"Drugs in R & D"},{"issue":"3","key":"pntd.0013404.ref039","doi-asserted-by":"crossref","first-page":"1584","DOI":"10.4049\/jimmunol.167.3.1584","article-title":"Immunostimulatory DNA-based vaccines elicit multifaceted immune responses against HIV at systemic and mucosal sites","volume":"167","author":"AA Horner","year":"2001","journal-title":"J Immunol"},{"issue":"6","key":"pntd.0013404.ref040","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1136\/thoraxjnl-2013-204605","article-title":"A limited CpG-containing oligodeoxynucleotide therapy regimen induces sustained suppression of allergic airway inflammation in mice","volume":"69","author":"JD Campbell","year":"2014","journal-title":"Thorax"},{"issue":"1","key":"pntd.0013404.ref041","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.vaccine.2005.08.095","article-title":"Comparison of the safety and immunogenicity of hepatitis B virus surface antigen co-administered with an immunostimulatory phosphorothioate oligonucleotide and a licensed hepatitis B vaccine in healthy young adults","volume":"24","author":"SA Halperin","year":"2006","journal-title":"Vaccine"},{"issue":"7","key":"pntd.0013404.ref042","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1016\/j.vaccine.2014.12.060","article-title":"Immunogenicity and safety of an investigational hepatitis B vaccine with a Toll-like receptor 9 agonist adjuvant (HBsAg-1018) compared with a licensed hepatitis B vaccine in patients with chronic kidney disease and type 2 diabetes mellitus","volume":"33","author":"JM Janssen","year":"2015","journal-title":"Vaccine"},{"issue":"4","key":"pntd.0013404.ref043","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1007\/s12250-013-3321-x","article-title":"Establishment and preliminary application of a rapid fluorescent focus inhibition test (RFFIT) for rabies virus","volume":"28","author":"P Yu","year":"2013","journal-title":"Virol Sin"},{"key":"pntd.0013404.ref044","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.jviromet.2015.03.022","article-title":"A recombinant rabies virus expressing a phosphoprotein-eGFP fusion is rescued and applied to the rapid virus neutralization antibody assay","volume":"219","author":"H-B Tang","year":"2015","journal-title":"J Virol Methods"},{"issue":"1","key":"pntd.0013404.ref045","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.jhep.2023.09.019","article-title":"Therapeutic vaccination with lentiviral vector in HBV-persistent mice and two inactive HBsAg carriers","volume":"80","author":"Y Zhang","year":"2024","journal-title":"J Hepatol"}],"container-title":["PLOS Neglected Tropical Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0013404","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T17:45:15Z","timestamp":1756230315000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0013404"}},"subtitle":[],"editor":[{"given":"Prashant","family":"Kumar","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2025,8,26]]},"references-count":45,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2025,8,26]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pntd.0013404","relation":{},"ISSN":["1935-2735"],"issn-type":[{"value":"1935-2735","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,26]]}}}