The human ACE-2 receptor binding domain of SARS-CoV-2 express on the viral surface of the Newcastle disease virus as a non-replicating viral vector vaccine candidate

Abstract

Since the SARS-CoV-2 infection was identified in December 2019, SARS-CoV-2 infection has rapidly spread worldwide and has become a significant pandemic disease. In addition, human death and serious health problem caused by SARS-CoV-2 infection, the socio-economic impact has been very serious. Here, we describe the development of the viral vector vaccine, which is the receptor-binding domain (RBD) of SARS-CoV-2 expressed on the surface of Newcastle disease virus (LVP-K1-RBD19). The RBD protein concentrations on the viral surface were measured by the sandwich ELISA method. 106.7 TCID50/ml of LVP-K1-RBD19 has a 0.17 μg of RBD protein. Optical density (OD) values of mouse sera inoculated with 10 μg of RBD protein expressed on the surface of LVP-K1-RBD19 generated 1.78-fold higher RBD-specific antibody titers than mice inoculated with 10 μg RBD protein with alum at 28 dpi. Moreover, mice inoculated with 10 μg of RBD protein expressed on the surface of LVP-K1-RBD19 virus showed more than 80% neutralization at 1:256 against the SARS-CoV-2 pseudovirus. These results demonstrated that inactivated LVP-K1-RBD19 virus produces neutralizing antibodies against SARS-CoV-2 in a short period and could be elect protective immunity in humans and LVP-K1-RBD19 will be a good candidate for the COVID-19 vaccine.

The tumor suppressive effect and apoptotic mechanism of TRAIL gene‐containing recombinant NDV in TRAIL‐resistant colorectal cancer HT‐29 cells and TRAIL‐nonresistant HCT116 cells, with each cell bearing a mouse model

“…The previously generated full-length cDNA clone of recombinant NDV (rNDV), which contained the transgene cassette inserted between the NP and P genes of the non-pathogenic NDV VG/GA strain), was used as the backbone to construct new cDNA. 22,36 The plasmid was linearized by restriction enzyme digestion to allow insertion of the extracellular form of the human TRAIL gene (amino acids 114-281). The TRAIL gene was amplified with NotI-GE-IG-GS-Kozak at the 3′-end and FseI at the 5′-end using the Phusion Flash High-Fidelity PCR Master Mix (cat.…”

Development and Scalable Production of Newcastle Disease Virus-Vectored Vaccines for Human and Veterinary Use

“…Combinations of intranasal and intramuscular doses have also been assessed for several vaccine candidates [ 30 , 31 , 70 , 76 ]. Inactivated NDV-vectored vaccines, on the other hand, have been administered exclusively by the intramuscular route, as the inactivated virus can no longer replicate in the mucosal passages [ 31 , 75 , 76 , 78 ].…”

“…NDV-vectored vaccines have great potential to be used against pandemic diseases, having shown efficient protection against EBOV [ 13 , 29 , 77 ], SARS-CoV [ 28 ] and SARS-CoV-2 [ 18 , 26 , 27 , 30 , 31 , 75 , 76 , 78 ]. Intranasal vaccines against EBOV have been shown to induce neutralizing antibody responses in monkeys [ 29 ], guinea pigs [ 13 ] and mice [ 77 ], although the latter study found more robust responses when mixing adenovirus and NDV-vectored doses as compared to a homologous NDV-vectored regimen.…”

“…A similar result was found in a study against SARS-CoV-2 in hamsters [ 27 ], in which two doses induced a protective neutralizing response while the single-dose regimen did not significantly reduce viral loads upon infection. Inactivated NDV-vectored SARS-CoV-2 vaccines have also been successful, inducing higher neutralizing responses in mice than a purified protein vaccine [ 78 ] and significantly reducing viral loads in a hamster model [ 75 ].…”

Assessing the risks associated with the emergence of Florona and possible preventive measures

“…Hence, the coinfection with influenza and SARS-CoV-2 can substantially increase fatality rates, particularly among the high-risk populations such as the elderly and immunocompromised patients. 3 Therefore, it is vital to assess the threats associated with the coexistence of influenza and SARS-CoV-2. So, in the following sections, we will focus on the risks and threats related to the Florona.…”