Vaccination With Recombinant Adenoviruses Expressing the Bluetongue Virus Subunits VP7 and VP2 Provides Protection Against Heterologous Virus Challenge.

José Manuel Rojas,Miguel Avia,Noemí Sevilla,Diego Barba-Moreno,Verónica Martín

doi:10.3389/fvets.2021.645561

Abstract

Bluetongue virus (BTV) is the causative agent of a disease that affects domestic and wild ruminants and leads to critical economic losses. BTV is an arbovirus from the Reoviridae family that is typically transmitted by the bite of infected Culicoides midges. BTV possesses multiple serotypes (up to 28 have been described), and immunity to one serotype offers little cross-protection to other serotypes. The design of vaccines that provide protection across multiple serotypes is therefore highly desirable to control this disease. We previously reported that a recombinant replication-defective human adenovirus serotype 5 (Ad5) that expresses the VP7 inner core protein of BTV serotype 8 (Ad5VP7-8) induced T-cell responses and provided protection. In the present work, we evaluated as BTV vaccine the combination of Ad5VP7-8 with another recombinant Ad5 that expresses the outer core protein VP2 from BTV-1 (Ad5VP2-1). The combination of Ad5VP2-1 and Ad5VP7-8 protected against homologous BTV challenge (BTV-1 and BTV-8) and partially against heterologous BTV-4 in a murine model. Cross-reactive anti-BTV immunoglobulin G (IgG) were detected in immunized animals, but no significant titers of neutralizing antibodies were elicited. The Ad5VP7-8 immunization induced T-cell responses that recognized all three serotypes tested in this study and primed cytotoxic T lymphocytes specific for VP7. This study further confirms that targeting antigenic determinant shared by several BTV serotypes using cellular immunity could help develop multiserotype BTV vaccines.

Highlights

Bluetongue (BT) is a disease of compulsory notification to the OIE (World Organization for Animal Health) that affects domestic and wild ruminants and causes important economic losses [1]
We aimed to evaluate the potential of replication-defective adenoviral vectors that express Bluetongue virus (BTV) variable outer capsid protein VP2 and the more conserved inner capsid protein VP7 as a vaccine against multiple BTV serotypes
We showed that a heterologous formulation can provide protection against several serotypes. This combination of adenoviral vectors protected against the challenge from the BTV serotypes used to produce the adenoviral vaccine vectors, and more intriguingly against a heterologous BTV challenge

Summary

Introduction

Bluetongue (BT) is a disease of compulsory notification to the OIE (World Organization for Animal Health) that affects domestic and wild ruminants and causes important economic losses [1]. Viremia is present in subclinically infected animals, and this is thought to act as a reservoir for the disease [2]. Bluetongue virus (BTV), the causative agent of this disease, is an arbovirus usually transmitted by the bite of Culicoides midges [1]. The redistribution of the competent vector Culicoides imicola across the Mediterranean Basin as well as the discovery that autochthonous Culicoides species can harbor and transmit the virus over winter have indicated that the disease can be considered endemic in Europe [6,7,8,9]. The economic impact of BTV is considerable and requires vaccination campaigns to keep outbreaks under control

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