Recombinant Human Adenovirus Type 5 Co-expressing RABV G and SFTSV Gn Induces Protective Immunity Against Rabies Virus and Severe Fever With Thrombocytopenia Syndrome Virus in Mice.

Xuexing Zheng,Lina Yan,Wenwen Zheng,Hongbin He,Li Tian,Yelei Zhu,Peilu Sun,Yurong Wei,Tong Xu,Zhongxin Zhao,Lele Liu

doi:10.3389/fmicb.2020.01473

Abstract

Both severe fever with thrombocytopenia syndrome (SFTS) and rabies are severe zoonotic diseases. As co-hosts of rabies virus (RABV) and SFTS virus (SFTSV), dogs and cats could not only be infected but also transmit the virus to human. Hence, developing a bivalent vaccine against both SFTS and rabies is urgently needed. In this study, we generated a recombinant replication-deficient human adenovirus type 5 (Ad5) co-expressing RABV G and SFTSV Gn (Ad5-G-Gn) and evaluated its immunogenicity and efficacy in mice. Ad5-G-Gn immunization activated more dendritic cells (DCs) and B cells in lymph nodes (LNs) and induced Th1-/Th2-mediated responses in splenocytes, leading to robust production of neutralizing antibodies against SFTSV and RABV. In addition, single dose of Ad5-G-Gn conferred mice complete protection against lethal RABV challenge and significantly reduced splenic SFTS viral load. Therefore, our data support further development of Ad5-G-Gn as a potential bivalent vaccine candidate against SFTS and rabies for dog and cat use.

Highlights

Severe fever with thrombocytopenia syndrome (SFTS), first reported in China in 2009, is an emerging zoonotic disease caused by a tick-borne, negative-stranded RNA virus, termed as severe fever with thrombocytopenia syndrome (SFTS) virus (SFTSV)
We cloned rabies virus (RABV)-G and SFTS virus (SFTSV)-Gn into adenovirus type 5 (Ad5) vector to generate the recombinant Ad5-G-Gn (Figure 1A), which was rescued in 293A cells
The recombinant Ad5-G-Gn was confirmed by examining RABV-G and SFTSV-Gn expression in Ad5-G-Gn infected 293T cells

Summary

INTRODUCTION

Severe fever with thrombocytopenia syndrome (SFTS), first reported in China in 2009, is an emerging zoonotic disease caused by a tick-borne, negative-stranded RNA virus, termed as SFTS virus (SFTSV). Developing vaccines for dog and cat use is urgent to effectively control SFTS. Vaccination of dogs and cats is the most efficient way to control human rabies. The genome of RABV is a single-stranded, non-segmented negative-sense RNA, which encodes five structural proteins: nucleoprotein (N), phosphoprotein (P), matrix protein (M), glycoprotein (G), and RNA-dependent RNA polymerase (L). G protein is the only protective antigen of RABV and can induce VNA production (Johnson et al, 2010) Both SFTS and rabies are serious zoonotic diseases and impose severe threat to public health. Given that SFTSV and RABV share hosts and rabies vaccine is compulsory for cats and dogs in China, development of a bivalent vaccine targeting both RABV and SFTSV could be a more promising strategy for the prevention of SFTS and rabies. Recombinant Ad5-G-Gn-induced dendritic cells (DCs) recruitment and activation and B and T cells activation, enhanced VNA production in mice

MATERIALS AND METHODS

RESULTS

DISCUSSION

DATA AVAILABILITY STATEMENT