Recombinant rabies virus with the glycoprotein fused with a DC-binding peptide is an efficacious rabies vaccine.

Yachun Zhang,Yingying Li,Min Cui,Zhen F Fu,Ming Zhou,Huanchun Chen,Ling Zhao,Zhaochen Luo

doi:10.18632/oncotarget.23160

Yachun Zhang, Yingying Li + Show 6 more

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https://doi.org/10.18632/oncotarget.23160

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Abstract

Our previous studies demonstrated that recruiting and/or activating dendritic cells (DCs) enhanced the immunogenicity of recombinant rabies viruses (rRABV). In this study, rRABV LBNSE with a small DC-binding peptide (designated as rLBNSE-DCBp) or a negative control peptide (designated as rLBNSE-DCCp) fused to the glycoprotein (G) was constructed and rescued. As expected, significantly more activated DCs were detected in rLBNSE-DCBp-immunized mice than those immunized with rLBNSE or rLBNSE-DCCp. Subsequently, significantly more generation of TFH and GC B cells were observed in rLBNSE-DCBp immunized mice than those in rLBNSE or rLBNSE-DCCp-immunized mice. In addition, significantly higher levels of virus neutralizing antibodies (VNAs) were observed in mice immunized with rLBNSE-DCBp than those immunized with rLBNSE or rLBNSE-DCCp, resulting in a better protection of rLBNSE-DCBp immunized mice against the lethal challenge. Taken together, our results suggest that rRABV with G fused with DCBp is a promising rabies vaccine candidate.

Highlights

Rabies is a zoonotic viral disease that causes more than 59,000 human deaths annually all over the world [1]
To further determine if increasing the binding efficiency of the recombinant rabies viruses (rRABV) to dendritic cells (DCs) is sufficient to enhance the immunogenicity of rabies virus (RABV), a small DC-binding peptide (DCBp) and a control peptide (DCCp, do not bind to DCs) that characterized in previous studies were inserted after the signal peptide of G protein of LBNSE strain by fusion PCR, and designated as rLBNSE-DCBp and rLBNSE-DCCp, respectively (Figure 1A)
Multi-step growth curves on BSR (Figure 1B) and NA (Figure 1C) cells were depicted, and the results show that the growth curves of rLBNSEDCBp and rLBNSE-DCCp were similar to the parent virus rLBNSE, indicating that the insertion of DCBp or DCCp into G did not affect the viral replication in vitro

Summary

Introduction

Rabies is a zoonotic viral disease that causes more than 59,000 human deaths annually all over the world [1]. Rabies virus (RABV), is a neurotropic virus, consisting of five genes nucleoprotein (N), phosphoprotein (P), matrix protein (M), glycoprotein (G) and the viral RNA polymerase (L) [2]. From the site of entry, RABV moves fast along the peripheral nervous system and reach the central nervous system (CNS) eventually. It is almost a death sentence once clinical signs appear [3]. It can be prevented by appropriate vaccination in humans and animals [4]. Millions of people are vaccinated globally and it is estimated that this saves more than 250,000 people from dying of rabies every year [6]

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