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Transient Expression of Biologically Active Anti-rabies Virus Monoclonal Antibody in Tobacco Leaves.

ABSTRACT: Background:Rabies virus is a neurotropic virus that causes fatal, but, a preventable disease in mammals. Administration of rabies immunoglobulin (RIG) is essential for the post-exposure of the prophylaxis to prevent the disease. However, replacement of polyclonal RIGs with alternative monoclonal antibodies (MAbs) that are capable of neutralizing rabies virus has been recommended. Objectives:Here, we have investigated the transient expression of the full-size human MAb against rabies virus glycoprotein; the MAb SO57 in the tobacco plants using vacuum agro-infiltration. Previously, stably transformed plants expressing the MAb have been reported. Materials and Methods:In this study three vectors carrying the codon-optimized genes for the heavy or light chain and p19 silencing-suppressor were constructed. These vectors were co-infiltrated into Nicotiana tabacum leaves and the transgenes were expressed. Results:Dot blot, Western blotting, ELISA, and in vitro neutralization assays of the plant extracts showed that the human MAb could assemble in tobacco leaves and was able to neutralize rabies virus. Conclusions:This study is the first report of transient expression of human MAb SO57 gene in tobacco plant within a few days after vacuum agro-infiltration.

SUBMITTER: Shafaghi M

PROVIDER: S-EPMC6217261 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Transient Expression of Biologically Active Anti-rabies Virus Monoclonal Antibody in Tobacco Leaves.

Shafaghi Mona M Maktoobian Somayeh S Rasouli Rahimeh R Howaizi Nader N Ofoghi Hamideh H Ehsani Parastoo P

Iranian journal of biotechnology 20180418 1

<h4>Background</h4>Rabies virus is a neurotropic virus that causes fatal, but, a preventable disease in mammals. Administration of rabies immunoglobulin (RIG) is essential for the post-exposure of the prophylaxis to prevent the disease. However, replacement of polyclonal RIGs with alternative monoclonal antibodies (MAbs) that are capable of neutralizing rabies virus has been recommended.<h4>Objectives</h4>Here, we have investigated the transient expression of the full-size human MAb against rabi ...[more]

PMID: 30555840

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Project description:BackgroundA vero cell-based inactivated Rabies Vaccine (Rabivax-S) and Rabies Human Monoclonal Antibody (Rabishield) have been approved since 2016. A post-marketing surveillance was conducted in India from 2020 to 2021 to gather real world safety data on Rabivax-S and Rabishield.MethodsThis was non-interventional active surveillance in patients with category III potential rabies exposure who were administered a post-exposure prophylaxis (PEP) regimen (Rabishield and Rabivax-S) by their healthcare providers (HCPs) as per the dosages and regimens mentioned in the package insert approved by the Indian regulators. The approved schedule for PEP was local infiltration of Rabishield on Day 0 and five doses of Rabivax-S on Day 0, 3, 7, 14, and 28 (Intramuscular route, IM) or four doses of Rabivax-S on Day 0, 3, 7, and 28 (Intradermal route, ID). The primary objective of this surveillance was to generate real-world evidence on the safety and tolerability of Rabishield and Rabivax-S. All patients enrolled in the surveillance were required to report any adverse events (AEs) occurring up to Day 31 after initiation of PEP (administration of Rabishield and the first dose of Rabivax-S) to their HCP.FindingsA total of 1000 patients with category III potential rabies exposure were enrolled across India. 991 patients received the PEP regimen with IM Rabivax-S while 9 received a PEP regimen with the ID regimen. While 32% of the patients were <12 years of age, 11.8% were ≥12 to <18 years of age and 56.2% were ≥18 years of age. The entire PEP regimen was completed by 97.3% of the enrolled patients. A total of 69 AEs were reported in 64 patients. Out of these, 49 AEs in 47 patients were assessed as causally related to the study products (26 with Rabishield and 23 with Rabivax-S). The majority of the AEs were mild and all recovered without any sequelae. One serious adverse event (SAE) of fracture of the hand was reported which was not related to either Rabishield or Rabivax-S. No case of rabies was reported.InterpretationRabishield and Rabivax-S have an excellent safety profile and are well tolerated. No participant developed rabies during 31 day follow up.FundingThe PMS was funded by Serum institute of India Private Limited which is the manufacturer of the study products.

Project description:Chikungunya fever, a mosquito-borne disease manifested by fever, rash, myalgia, and arthralgia, is caused by chikungunya virus (CHIKV), which belongs to the genus Alphavirus of the family Togaviridae Anti-CHIKV IgG from convalescent patients is known to directly neutralize CHIKV, and the state of immunity lasts throughout life. Here, we examined the epitope of a neutralizing mouse monoclonal antibody against CHIKV, CHE19, which inhibits viral fusion and release. In silico docking analysis showed that the epitope of CHE19 was localized in the viral E2 envelope and consisted of two separate segments, an N-linker and a ?-ribbon connector, and that its bound Fab fragment on E2 overlapped the position that the E3 glycoprotein originally occupied. We showed that CHIKV-E2 is lost during the viral internalization and that CHE19 inhibits the elimination of CHIKV-E2. These findings suggested that CHE19 stabilizes the E2-E1 heterodimer instead of E3 and inhibits the protrusion of the E1 fusion loop and subsequent membrane fusion. In addition, the antigen-bound Fab fragment configuration showed that CHE19 connects to the CHIKV spikes existing on the two individual virions, leading us to conclude that the CHE19-CHIKV complex was responsible for the large virus aggregations. In our subsequent filtration experiments, large viral aggregations by CHE19 were trapped by a 0.45-?m filter. This virion-connecting characteristic of CHE19 could explain the inhibition of viral release from infected cells by the tethering effect of the virion itself. These findings provide clues toward the development of effective prophylactic and therapeutic monoclonal antibodies against the Alphavirus infection.IMPORTANCE Recent outbreaks of chikungunya fever have increased its clinical importance. Neither a specific antiviral drug nor a commercial vaccine for CHIKV infection are available. Here, we show a detailed model of the docking between the envelope glycoprotein of CHIKV and our unique anti-CHIKV-neutralizing monoclonal antibody (CHE19), which inhibits CHIKV membrane fusion and virion release from CHIKV-infected cells. Homology modeling of the neutralizing antibody CHE19 and protein-protein docking analysis of the CHIKV envelope glycoprotein and CHE19 suggested that CHE19 inhibits the viral membrane fusion by stabilizing the E2-E1 heterodimer and inhibits virion release by facilitating the formation of virus aggregation due to the connecting virions, and these predictions were confirmed by experiments. Sequence information of CHE19 and the CHIKV envelope glycoprotein and their docking model will contribute to future development of an effective prophylactic and therapeutic agent.

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Transient Expression of Biologically Active Anti-rabies Virus Monoclonal Antibody in Tobacco Leaves.

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Transient Expression of Biologically Active Anti-rabies Virus Monoclonal Antibody in Tobacco Leaves.

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