A protective bivalent vaccine against Rift Valley fever and bluetongue

Eva Calvo-Pinilla,Rafael Blasco,Alejandro Marín-López,Luis Jiménez-Cabello,Gema Lorenzo,Alejandro Brun,Javier Ortego,Sandra Moreno,Sergio Utrilla-Trigo,Aitor Nogales,Julio Benavides

doi:10.1038/s41541-020-00218-y

Abstract

Rift Valley fever (RVF) and bluetongue (BT) are two important ruminant diseases transmitted by arthropods. Both viruses have shown important geographic spread leading to endemicity of BT virus (BTV) in Africa and Europe. In this work, we report a dual vaccine that simultaneously induces protective immune responses against BTV and RVFV based on modified vaccinia Ankara virus (MVA) expressing BTV proteins VP2, NS1, or a truncated form of NS1 (NS1-Nt), and RVFV Gn and Gc glycoproteins. IFNAR(−/−) mice immunized with two doses of MVA-GnGc-VP2 developed a significant neutralizing antibody response against BTV-4 and RVFV. Furthermore, the homologous prime-boost immunization with MVA-GnGc-NS1 or MVA-GnGc-NS1-Nt triggered neutralizing antibodies against RVFV and NS1-specific cytotoxic CD8+ T cells in mice. Moreover, all mice immunized with MVA-GnGc-NS1 or MVA-GnGc-NS1-Nt remained healthy after lethal challenge with RVFV or BTV-4. The homologous prime-boost vaccination with MVA-GnGc-NS1, which was the best immunization strategy observed in mice, was assayed in sheep. Clinical signs and viremia were absent or highly reduced in vaccinated sheep after challenge with BTV-4 or RVFV. These results indicate that MVA-GnGc-NS1 vaccination elicits immune protection against RVFV and BTV in sheep.

Highlights

Ruminants are affected by a variety of viral infections, including Rift Valley fever virus (RVFV) and bluetongue virus (BTV)
RVFV is mainly present in Africa, recent outbreaks in the Middle East have demonstrated its potential to spread beyond the African continent[2]
A RVFV GnGc polyprotein sequence was inserted into the F13L locus, while the BTV segments were cloned into the TK locus, generating the modified vaccinia Ankara virus (MVA)-GnGc-VP2, MVAGnGc-NS1, and MVA-GnGc-NS1-Nt constructs as described in “Methods” section

Summary

Introduction

Ruminants are affected by a variety of viral infections, including Rift Valley fever virus (RVFV) and bluetongue virus (BTV). These pathogens cause epidemics of severe disease, in sheep, with serious implications for agricultural livestock and trade. RVFV is mainly present in Africa, recent outbreaks in the Middle East have demonstrated its potential to spread beyond the African continent[2]. The use of multivalent vaccines that could provide immunity against a prevalent disease for which vaccination is mandatory, i.e., BTV in Europe, while immunizing against other diseases of more sporadic nature, such as RVFV would be a potential strategy to overcome this problem and to reduce the cost of vaccine production

Methods

Results

Conclusion