Abstract
Rabies is a neurological disease with 100% lethality. Some of the rare human patients who survived after multiple drug treatment had severe sequelae. The present study showed that after 48 h of RABV inoculation, mice injected intracerebrally with anti-RABV F (ab’)2 plus Bioporter® showed 70% survival compared to the control group, suggesting that transfection of anti-RABV antibodies to the brain may prevent or delay the spread of RABV at an early stage of infection. This result may provide important protocol results in intracellular antibody delivery to prevent the fatal outcome of the disease.
References
Burton EC, Burns DK, Opatowsky MJ, el-Feky WH, Fischbach B, Melton L, Sanchez E, Randall H, Watkins DL, Chang J, Klintmalm G (2005) Rabies encephalomyelitis: E clinical, neuroradiological, and pathological findings in 4 transplant recipients. Arch Neurol 62(6):873–882. https://doi.org/10.1001/archneur.62.6.873
Davis BM, Rall GF, Schnell MJ (2015) Everything you always wanted to know about rabies virus (but were afraid to ask). Annu Rev Virol 2(1):451–471. https://doi.org/10.1146/annurev-virology-100114-055157
Fuoco NL, Dos Ramos SS, Fernandes ER, Luiz FG, Ribeiro OG, Katz ISS (2018) Infection of neuroblastoma cells by rabies virus is modulated by the virus titer. Antivir Res 49:89–94. https://doi.org/10.1016/j.antiviral.2017.11.003
Hampson K, Coudeville L, Lembo T, Sambo M, Kieffer A, Attlan M, Barrat J, Blanton JD, Briggs DJ, Cleaveland S, Costa P, Freuling CM, Hiby E, Knopf L, Leanes F, Meslin FX, Metlin A, Miranda ME, Müller T, Nel LH, Recuenco S, Rupprecht CE, Schumacher C, Taylor L, Vigilato MAN, Zinsstag J, Dushoff J, on behalf of the Global Alliance for Rabies Control Partners for Rabies Prevention (2015) Estimating the global burden of endemic canine rabies. PLoS Negl Trop Dis 9(4):e0003709. https://doi.org/10.1371/journal.pntd.0003709
Ho JK, White PJ, Pouton CW (2018) Self-crosslinking lipopeptide/DNA/PEGylated particles: a new platform for DNA vaccination designed for assembly in aqueous solution. Mol Ther Nucleic Acids 12:891–892. https://doi.org/10.1016/j.omtn.2018.05.025
Hooper DC, Phares TW, Fabis MJ, Roy A (2009) The production of antibody by invading B cells is required for the clearance of rabies virus from the central nervous system. PLoS Negl Trop Dis 3(10):1–8. https://doi.org/10.1371/journal.pntd.0000535
Jackson AC, Wunner WH (2007) Rabies. Academic Press, London
Kawai JGC (2012) Transfection of anti-rabies antibodies into n2a lineage cells (mouse neuroblastoma) and intracellular neutralization for use as an antiviral. Postdoctoral, University of São Paulo
Lewis P, Fu Y, Lentz TL (2000) Rabies virus entry at the neuromuscular junction in nerve-muscle cocultures. Muscle Nerve 23(95):720–730. https://doi.org/10.1002/(SICI)1097-4598(200005)23:5<720::AID-MUS9>3.0.CO;2-5
Manoj S, Mukherjee A, Johri S, Kumar KV (2016) Recovery from rabies, a universally fatal disease. Mil Med Res 3:21. https://doi.org/10.1186/s40779-016-0089-y
Marosi A, Dufkova L, Forró B, Felde O, Erdélyi K, Širmarová J, Palus M, Hönig V, Salát J, Tikos R, Gyuranecz M, Růžek D, Martina B, Koraka P, Osterhaus ADME, Bakonyi T (2018) Combination therapy of rabies-infected mice with inhibitors of pro-inflammatory host response, antiviral compounds and human rabies immunoglobulin. Vaccine. 37(33):4724–4735. https://doi.org/10.1016/j.vaccine.2018.05.066
Prasad S, Lokensgard JR (2019) Brain-resident t cells following viral infection. 32(1):48–54. https://doi.org/10.1089/vim.2018.0084
PROMED (2009) Rabies, human survival, bat-Brazil. https://www.promedmail.org/post/20090919.3292
van Thiel PP, de Bie RM, Eftimov F et al (2009) Fatal human rabies due to Duvenhage virus from a bat in Kenya: failure of treatment with coma-induction, ketamine, and antiviral drugs. PLoS Negl. Trop. Dis. 3(7):e428. https://doi.org/10.1371/journal.pntd.0000428
Weill CO, Biri S, Erbacher P (2008) Cationic lipid-mediated intracellular delivery of antibodies into live cells. Biotechniques. 44(7):7–11. https://doi.org/10.2144/000112832
WHO (2013) Expert consultation on rabies: second Report. World Health Organization, Geneva
Willoughby RE, Tieves KS, Hoffman GM et al (2005) Survival after treatment of rabies with induction of coma. N Engl J Med 352(24):2508–2514. https://doi.org/10.1056/NEJMoa050382
Funding
The authors are thankful for the financial support provided by CNPq (Brazilian National Board for Scientific and Technological Development) grant number 307291/2017-0 and CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Brazil) Finance Code 001, which had no role in the study design, collection, analysis and interpretation of data, writing of the report, and in the decision to submit the article for publication.
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This experiment was approved by the Ethics Committee on Animal Use (CEUA) of the School of Veterinary Medicine and Animal Science - University of São Paulo (FMVZ-USP), under protocol no. 9658071016. All mice were used for the experiments; prior to any procedure, mice were anesthetized with isofluoran.
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Agostinho, W.C., Brandão, P.E. Intracerebral transfection of anti-rabies virus antibodies is an effective therapy for rabies. J. Neurovirol. 26, 764–768 (2020). https://doi.org/10.1007/s13365-020-00883-8
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DOI: https://doi.org/10.1007/s13365-020-00883-8