Characterization of Two Neutralizing Antibodies against Rift Valley Fever Virus Gn Protein.

Meng Hao,Yunzhu Dong,Zhengshan Chen,Shuling Liu,Pengfei Fan,Xiangyang Chi,Yujiao Liu,Xianzhu Xia,Changming Yu,Jianmin Li,Shengnan Zhang,Guanying Zhang,Yi Chen,Xiaohong Song

doi:10.3390/v12030259

Abstract

The Rift Valley fever virus (RVFV) is an arthropod-borne virus that can not only cause severe disease in domestic animals but also in humans. However, the licensed vaccines or available therapeutics for humans do not exist. Here, we report two Gn-specific neutralizing antibodies (NAbs), isolated from a rhesus monkey immunized with recombinant human adenoviruses type 4 expressing Rift Valley fever virus Gn and Gc protein (rHAdV4-GnGcopt). The two NAbs were both able to protect host cells from RVFV infection. The interactions between NAbs and Gn were then characterized to demonstrate that these two NAbs might preclude RVFV glycoprotein rearrangement, hindering the exposure of fusion loops in Gc to endosomal membranes after the virus invades the host cell. The target region for the two NAbs is located in the Gn domain III, implying that Gn is a desired target for developing vaccines and neutralizing antibodies against RVFV.

Highlights

The Rift Valley fever virus (RVFV), a member of the Phlebovirus genus in the order Bunyavirales, poses a threat to both human and livestock health
Two neutralizing antibodies (NAbs) that target Gn proteins were isolated from a rhesus monkey immunized with recombinant human adenoviruses type 4 expressing RVFV Gn and Gc proteins
Peripheral blood mononuclear cells (PBMCs) and sera were isolated from a rhesus monkey that was immunized with rHAdV4-GnGcopt after 210 days, and PBMCs were stored in liquid nitrogen for further use

Summary

Introduction

The Rift Valley fever virus (RVFV), a member of the Phlebovirus genus in the order Bunyavirales, poses a threat to both human and livestock health. The clinical symptoms caused by RVFV infection can differ according to the severity of the infection, including being asymptomatic (in 30%–60% of cases) or causing a weeklong unexplained febrile illness, severe hemorrhagic fever, encephalitis, retinitis, and potentially death [1]. Since this virus was first isolated in 1931, epidemics have been reported on the African continent, such as in Egypt, South Africa, Mauritania, and East Africa [2,3,4,5].

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