Recombinant Rift Valley fever viruses encoding bluetongue virus (BTV) antigens: Immunity and efficacy studies upon a BTV-4 challenge

PLoS Negl Trop Dis. 2020 Dec 4;14(12):e0008942. doi: 10.1371/journal.pntd.0008942. eCollection 2020 Dec.

Abstract

Background: Many ruminant diseases of viral aetiology can be effectively prevented using appropriate vaccination measures. For diseases such as Rift Valley fever (RVF) the long inter-epizootic periods make routine vaccination programs unfeasible. Coupling RVF prophylaxis with seasonal vaccination programmes by means of multivalent vaccine platforms would help to reduce the risk of new RVF outbreaks.

Methodology/principal findings: In this work we generated recombinant attenuated Rift Valley fever viruses (RVFVs) encoding in place of the virulence factor NSs either the VP2 capsid protein or a truncated form of the non-structural NS1 protein of bluetongue virus serotype 4 (BTV-4). The recombinant viruses were able to carry and express the heterologous BTV genes upon consecutive passages in cell cultures. In murine models, a single immunization was sufficient to protect mice upon RVFV challenge and to elicit a specific immune response against BTV-4 antigens that was fully protective after a BTV-4 boost. In sheep, a natural host for RVFV and BTV, both vaccines proved immunogenic although conferred only partial protection after a virulent BTV-4 reassortant Morocco strain challenge.

Conclusions/significance: Though additional optimization will be needed to improve the efficacy data against BTV in sheep, our findings warrant further developments of attenuated RVFV as a dual vaccine platform carrying heterologous immune relevant antigens for ruminant diseases in RVF risk areas.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Viral / immunology*
  • Antigens, Viral / immunology*
  • Bluetongue / prevention & control*
  • Bluetongue / virology
  • Bluetongue virus / genetics
  • Bluetongue virus / immunology*
  • Capsid Proteins / genetics
  • Capsid Proteins / immunology
  • Female
  • Immunity
  • Mice
  • Reassortant Viruses
  • Rift Valley Fever / prevention & control*
  • Rift Valley Fever / virology
  • Rift Valley fever virus / genetics
  • Serogroup
  • Sheep
  • Vaccination / veterinary*
  • Vaccines, Attenuated / immunology
  • Viral Nonstructural Proteins / genetics
  • Viral Nonstructural Proteins / immunology
  • Viral Vaccines / immunology*

Substances

  • Antibodies, Viral
  • Antigens, Viral
  • Capsid Proteins
  • Vaccines, Attenuated
  • Viral Nonstructural Proteins
  • Viral Vaccines

Grants and funding

AB is supported by grants AGL2014-57430R and AGL2017-83226R from the Spanish Ministry of Science, and grant S2018/BAA 4370 from Comunidad de Madrid R&D in Technologies Program. JO is supported by grants AGL2014-57430R and AGL2017-82570R from the Spanish Ministry of Science and Innovation and European Union’s Horizon 2020 research and innovation program under grant proposal 727393-2. SMF is a recipient of a pre-doctoral fellowship program from the Spanish Ministry of Science and innovation. FW is supported by the CCHF Vaccine consortium that has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement no. 732732, and by the Swedish Research Council (Vetenskapsrådet, VR) section Research Environment, Infection Biology (contract number 2018-05766). The funding sources had no involvement in the study design nor in the writing of the report and the decision to submit the article for publication.