{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T11:03:07Z","timestamp":1790247787801,"version":"4.1.0"},"reference-count":44,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2019,9,27]],"date-time":"2019-09-27T00:00:00Z","timestamp":1569542400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>There is a global need for effective and affordable rabies vaccines, which is unmet by current vaccines due to limitations in their production capacities, required administration schedules, storage requirements, and cost. Many different experimental approaches previously used for bacterial and viral vaccines have been applied to rabies, but with variable success. One of the most promising new concepts is the use of messenger RNA (mRNA) in encoding the main rabies virus antigen, the envelope glycoprotein (RABV-G). CureVac has applied their proprietary technology platform for the production of mRNA to this problem, resulting in the rabies vaccine candidate CV7201. Following preclinical studies in mice and pigs showing that CV7201 could induce neutralizing immune responses that protected against rabies virus, different dosages and routes of administration of CV7201 were tested in a phase 1 human study. This clinical study proved that mRNA vaccination was safe and had an acceptable reactogenicity profile, but immune responses depended on the mode of administration, and they did not unequivocally support CV7201 for further development as a prophylactic vaccine with this particular formulation. Further, preclinical studies using RABV-G mRNA encapsulated in lipid nanoparticles (LNPs) showed an improved response in both mice and nonhuman primates, and these encouraging results are currently being followed up in clinical studies in humans. This review summarizes the recent advances in mRNA vaccines against rabies.<\/jats:p>","DOI":"10.3390\/vaccines7040132","type":"journal-article","created":{"date-parts":[[2019,9,27]],"date-time":"2019-09-27T11:14:35Z","timestamp":1569582875000},"page":"132","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":84,"title":["Advances in RNA Vaccines for Preventive Indications: A Case Study of a Vaccine against Rabies"],"prefix":"10.3390","volume":"7","author":[{"given":"Nicole","family":"Armbruster","sequence":"first","affiliation":[{"name":"Scientist Prophylactic Vaccines Non-Clinical Development, CureVac AG, Paul-Ehrlich-Stra\u00dfe 15, D-72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edith","family":"Jasny","sequence":"additional","affiliation":[{"name":"Senior Scientist Prophylactic Vaccines Non-Clinical Development, CureVac AG, Paul-Ehrlich-Stra\u00dfe 15, D-72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Petsch","sequence":"additional","affiliation":[{"name":"Senior Director Prophylactic Vaccines Research, CureVac AG, Paul-Ehrlich-Stra\u00dfe 15, D-72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,9,27]]},"reference":[{"key":"ref_1","first-page":"13","article-title":"Human rabies transmitted by dogs: Current status of global data, 2015","volume":"91","author":"Fahrion","year":"2016","journal-title":"Wkly. Epidemiol. Rec."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/j.antiviral.2017.03.013","article-title":"The history of rabies in the Western Hemisphere","volume":"146","author":"Mauldin","year":"2017","journal-title":"Antivir. Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"671","DOI":"10.4065\/79.5.671","article-title":"Overview, prevention, and treatment of rabies","volume":"79","author":"Hankins","year":"2004","journal-title":"Mayo Clin. Proc."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.actatropica.2015.12.007","article-title":"Difficulties in estimating the human burden of canine rabies","volume":"165","author":"Taylor","year":"2017","journal-title":"Acta Trop."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Hampson, K., Coudeville, L., and Lembo, T. (2015). Global Alliance for Rabies Control Partners for Rabies Prevention. Estimating the global burden of endemic canine rabies. PLoS Negl. Trop. Dis., 9.","DOI":"10.1371\/journal.pntd.0003786"},{"key":"ref_6","first-page":"765","article-title":"M\u00e9thode pour pr\u00e9venir la rage apr\u00e8s morsure","volume":"101","author":"Pasteur","year":"1885","journal-title":"L\u2019Academie Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1111\/j.1365-2249.2012.04592.x","article-title":"Developments in rabies vaccines","volume":"169","author":"Hicks","year":"2012","journal-title":"Clin. Exp. Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1597","DOI":"10.1586\/erv.11.140","article-title":"From brain passage to cell adaptation: The road of human rabies vaccine development","volume":"10","author":"Wu","year":"2011","journal-title":"Exp. Rev. Vaccines"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/0022-510X(89)90192-5","article-title":"Semple rabies vaccine: Presence of myelin basic protein and proteolipid protein and its activity in experimental allergic encephalomyelitis","volume":"93","author":"Javier","year":"1989","journal-title":"J. Neurol. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Diallo, M.K., Diallo, A.O., Dicko, A., Richard, V., and Espi\u00e9, E. (2019). Human rabies post exposure prophylaxis at the Pasteur Institute of Dakar, Senegal: Trends and risk factors. BMC Infect. Dis., 19.","DOI":"10.1186\/s12879-019-3928-0"},{"key":"ref_11","unstructured":"WHO (2010). Rabies vaccines: WHO position paper. Wkly. Epidemiol. Rec., 85, 309\u2013320."},{"key":"ref_12","unstructured":"(2019, May 10). WHO Guide for Rabies Pre and Post Exposure Prophylaxis in Humans. Available online: https:\/\/www.who.int\/rabies\/PEP_Prophylaxis_guideline_15_12_2014.pdf."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"7162","DOI":"10.1016\/j.vaccine.2009.09.036","article-title":"Rabies post-exposure prophylaxis with purified equine rabies immunoglobulin: One-year follow-up of patients with laboratory-confirmed category III rabies exposure in the Philippines","volume":"27","author":"Quiambao","year":"2009","journal-title":"Vaccine"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1709","DOI":"10.1016\/j.vaccine.2004.09.027","article-title":"Reducing the cost of post-exposure rabies prophylaxis: Efficacy of 0.1 ml PCEC rabies vaccine administered intradermally using the Thai Red Cross post-exposure regimen in patients severely exposed to laboratory-confirmed rabid animals","volume":"23","author":"Quiambao","year":"2005","journal-title":"Vaccine"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/0042-6822(88)90600-9","article-title":"Completion of the rabies virus genome sequence determination: Highly conserved domains among the L (polymerase) proteins of unsegmented negative-strand RNA viruses","volume":"165","author":"Tordo","year":"1988","journal-title":"Virology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"S739","DOI":"10.1093\/clinids\/10.Supplement_4.S739","article-title":"Animal models in the pathogenesis and treatment of rabies","volume":"10","author":"Baer","year":"1988","journal-title":"Rev. Infect. Dis."},{"key":"ref_17","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":"Astray","year":"2017","journal-title":"Arch. Virol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Fooks, A.R., Banyard, A.C., and Ertl, H.C.J. (2018). New human rabies vaccines in the pipeline. Vaccine.","DOI":"10.1016\/j.vaccine.2018.08.039"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"202","DOI":"10.7774\/cevr.2014.3.2.202","article-title":"Immunogenicity and efficacy of a plasmid DNA rabies vaccine incorporating Myd88 as a genetic adjuvant","volume":"3","author":"Ullas","year":"2014","journal-title":"Clin. Exp. Vaccine Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1016\/j.ymthe.2019.01.020","article-title":"mRNA as a transformative technology for vaccine development to control infectious diseases","volume":"27","author":"Maruggi","year":"2019","journal-title":"Mol. Ther."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1038\/nrd.2017.243","article-title":"mRNA vaccines\u2014A new era in vaccinology","volume":"17","author":"Pardi","year":"2018","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.omtn.2019.01.013","article-title":"Optimization of lipid nanoparticles for intramuscular administration of mRNA vaccines","volume":"15","author":"Hassett","year":"2019","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"594","DOI":"10.3389\/fimmu.2019.00594","article-title":"Advances in mRNA vaccines for infectious diseases","volume":"10","author":"Zhang","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2649","DOI":"10.1016\/j.vaccine.2009.02.071","article-title":"Vaccine-derived poliovirus (VDPV): Impact on poliomyelitis eradication","volume":"27","author":"Minor","year":"2009","journal-title":"Vaccine"},{"key":"ref_25","unstructured":"WHO (2019, June 26). WHO Global Action Plan to Minimize Poliovirus Facility-Associated Risk After Type-Specific Eradication of Wild Polioviruses and Sequential Cessation of Oral Polio Vaccine Use (GAPIII)\u20142015. WHO\/POLIO\/15.05. Available online: http:\/\/polioeradication.org\/wp-content\/uploads\/2016\/12\/GAPIII_2014.pdf."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1097\/CJI.0b013e3181f7dbe8","article-title":"Messenger RNA-based vaccines with dual activity induce balanced TLR-7 dependent adaptive immune responses and provide antitumor activity","volume":"34","author":"Duchardt","year":"2011","journal-title":"J. Immunother."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1210","DOI":"10.1038\/nbt.2436","article-title":"Protective efficacy of in vitro synthesized, specific mRNA vaccines against influenza A virus infection","volume":"30","author":"Petsch","year":"2012","journal-title":"Nat. Biotechnol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.4161\/rna.22269","article-title":"Developing mRNA-vaccine technologies","volume":"9","author":"Schlake","year":"2012","journal-title":"RNA Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"269","DOI":"10.4049\/jimmunol.110.1.269","article-title":"Antigenic properties of rabies virus components","volume":"110","author":"Wiktor","year":"1973","journal-title":"J. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/S0092-1157(84)80019-0","article-title":"A new inactivated tissue culture rabies vaccine for use in man. Evaluation of PCEC-vaccine by laboratory tests","volume":"12","author":"Barth","year":"1984","journal-title":"J. Biol. Stand."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Schnee, M., Vogel, A.B., and Voss, D. (2016). An mRNA vaccine encoding rabies virus glycoprotein induces protection against lethal infection in mice and correlates of protection in adult and newborn pigs. PLoS Negl. Trop. Dis., 10.","DOI":"10.1371\/journal.pntd.0004746"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1097\/01.shk.0000142249.08135.e9","article-title":"Innate immune response in Th1- and Th2-dominant mouse strains","volume":"22","author":"Watanabe","year":"2004","journal-title":"Shock"},{"key":"ref_33","unstructured":"Meslin, F.-X., Kaplan, M.M., and Koprowski, H. (1996). Laboratory Techniques in Rabies, WHO. [4th ed.]."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.1016\/S0140-6736(17)31665-3","article-title":"Safety and immunogenicity of a mRNA rabies vaccine in healthy adults: An open-label, non-randomised, prospective, first-in-human phase 1 clinical trial","volume":"390","author":"Alberer","year":"2017","journal-title":"Lancet"},{"key":"ref_35","unstructured":"WHO (2019, September 10). WHO Expert Consultation on Rabies First Report 2004. Available online: http:\/\/www.who.int\/rabies\/trs931_%2006_05.pdf."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1038\/nbt.3187","article-title":"COMPASS identifies T-cell subsets correlated with clinical outcomes","volume":"33","author":"Lin","year":"2015","journal-title":"Nat. Biotechnol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2139","DOI":"10.1099\/0022-1317-78-9-2139","article-title":"Protection of pigs against Aujeszky\u2019s disease by DNA vaccination","volume":"78","author":"Gerdts","year":"1997","journal-title":"J. Gen. Virol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/S0264-410X(97)00198-9","article-title":"Comparison of DNA application methods to reduce BRSV shedding in cattle","volume":"16","author":"Schrijver","year":"1998","journal-title":"Vaccine"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1016\/j.vaccine.2018.12.049","article-title":"Needle-free delivery of DNA: Targeting of hemagglutinin to MHC class II molecules protects rhesus macaques against H1N1 influenza","volume":"37","author":"Mooij","year":"2019","journal-title":"Vaccine"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"14604","DOI":"10.1073\/pnas.1209367109","article-title":"Nonviral delivery of self-amplifying RNA vaccines","volume":"109","author":"Geall","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1038\/s41541-017-0032-6","article-title":"Unmodified mRNA in LNPs constitutes a competitive technology for prophylactic vaccines","volume":"2","author":"Lutz","year":"2017","journal-title":"NPJ Vaccines"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1111\/j.0022-202X.2005.23841.x","article-title":"Chemokines: Key players in innate and adaptive immunity","volume":"125","author":"Esche","year":"2005","journal-title":"J. Investig. Dermatol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1016\/j.ymthe.2019.02.012","article-title":"Delivering the messenger: Advances in technologies for therapeutic mRNA delivery","volume":"27","author":"Kowalski","year":"2019","journal-title":"Mol. Ther."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1963","DOI":"10.3389\/fimmu.2018.01963","article-title":"New vaccine technologies to combat outbreak situations","volume":"9","author":"Rauch","year":"2018","journal-title":"Front. Immunol."}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/7\/4\/132\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:25:16Z","timestamp":1760189116000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/7\/4\/132"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,9,27]]},"references-count":44,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["vaccines7040132"],"URL":"https:\/\/doi.org\/10.3390\/vaccines7040132","relation":{},"ISSN":["2076-393X"],"issn-type":[{"value":"2076-393X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,9,27]]}}}