A Protective Bivalent Vaccine Against Rift Valley Fever and Bluetongue

Overview

Journal NPJ Vaccines

Date 2020 Aug 15

PMID 32793399

Citations 20

Authors

Eva Calvo-Pinilla

Alejandro Marin-Lopez

Sandra Moreno

Gema Lorenzo

Sergio Utrilla-Trigo

Luis Jimenez-Cabello

Julio Benavides

Aitor Nogales

Rafael Blasco

Alejandro Brun

Javier Ortego

Affiliations

Soon will be listed here.

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.

Citing Articles

Novel replication-competent reporter-expressing Rift Valley fever viruses for molecular studies.

Nogales A, Alonso C, Moreno S, Lorenzo G, Borrego B, Martinez-Sobrido L J Virol. 2024; 99(1):e0178224.

PMID: 39665546 PMC: 11784304. DOI: 10.1128/jvi.01782-24.

Vaccine candidates based on MVA viral vectors expressing VP2 or VP7 confer full protection against Epizootic hemorrhagic disease virus in IFNAR(-/-) mice.

Jimenez-Cabello L, Utrilla-Trigo S, Rodriguez-Sabando K, Carra-Valenzuela A, Illescas-Amo M, Calvo-Pinilla E J Virol. 2024; 98(12):e0168724.

PMID: 39508577 PMC: 11650994. DOI: 10.1128/jvi.01687-24.

Co-expression of VP2, NS1 and NS2-Nt proteins by an MVA viral vector induces complete protection against bluetongue virus.

Jimenez-Cabello L, Utrilla-Trigo S, Calvo-Pinilla E, Lorenzo G, Illescas-Amo M, Benavides J Front Immunol. 2024; 15:1440407.

PMID: 39072326 PMC: 11272488. DOI: 10.3389/fimmu.2024.1440407.

IFNAR(-/-) Mice Constitute a Suitable Animal Model for Epizootic Hemorrhagic Disease Virus Study and Vaccine Evaluation.

Jimenez-Cabello L, Utrilla-Trigo S, Benavides-Silvan J, Anguita J, Calvo-Pinilla E, Ortego J Int J Biol Sci. 2024; 20(8):3076-3093.

PMID: 38904031 PMC: 11186350. DOI: 10.7150/ijbs.95275.

Evaluation of a Combined Live Attenuated Vaccine against Lumpy Skin Disease, Contagious Bovine Pleuropneumonia and Rift Valley Fever.

Bamouh Z, Elarkam A, Elmejdoub S, Hamdi J, Boumart Z, Smith G Vaccines (Basel). 2024; 12(3).

PMID: 38543936 PMC: 10975446. DOI: 10.3390/vaccines12030302.

References

Marin-Lopez A, Calvo-Pinilla E, Barriales D, Lorenzo G, Brun A, Anguita J . CD8 T Cell Responses to an Immunodominant Epitope within the Nonstructural Protein NS1 Provide Wide Immunoprotection against Bluetongue Virus in IFNAR Mice. J Virol. 2018; 92(16). PMC: 6069212. DOI: 10.1128/JVI.00938-18. View

Dungu B, Potgieter C, von Teichman B, Smit T . Vaccination in the control of bluetongue in endemic regions: the South African experience. Dev Biol (Basel). 2005; 119:463-72. View

Toussaint J, Sailleau C, Breard E, Zientara S, De Clercq K . Bluetongue virus detection by two real-time RT-qPCRs targeting two different genomic segments. J Virol Methods. 2007; 140(1-2):115-23. DOI: 10.1016/j.jviromet.2006.11.007. View

Odendaal L, Clift S, Fosgate G, Davis A . Lesions and Cellular Tropism of Natural Rift Valley Fever Virus Infection in Adult Sheep. Vet Pathol. 2018; 56(1):61-77. DOI: 10.1177/0300985818806049. View

Marin-Lopez A, Barreiro-Pineiro N, Utrilla-Trigo S, Barriales D, Benavente J, Nogales A . Cross-protective immune responses against African horse sickness virus after vaccination with protein NS1 delivered by avian reovirus muNS microspheres and modified vaccinia virus Ankara. Vaccine. 2019; 38(4):882-889. DOI: 10.1016/j.vaccine.2019.10.087. View

Perez P, Marin M, Lazaro-Frias A, Jimenez de Oya N, Blazquez A, Escribano-Romero E . A Vaccine Based on a Modified Vaccinia Virus Ankara Vector Expressing Zika Virus Structural Proteins Controls Zika Virus Replication in Mice. Sci Rep. 2018; 8(1):17385. PMC: 6255889. DOI: 10.1038/s41598-018-35724-6. View

Faburay B, Gaudreault N, Liu Q, Davis A, Shivanna V, Sunwoo S . Development of a sheep challenge model for Rift Valley fever. Virology. 2016; 489:128-40. DOI: 10.1016/j.virol.2015.12.003. View

Mertens P, Pedley S, Cowley J, Burroughs J, Corteyn A, Jeggo M . Analysis of the roles of bluetongue virus outer capsid proteins VP2 and VP5 in determination of virus serotype. Virology. 1989; 170(2):561-5. DOI: 10.1016/0042-6822(89)90447-9. View

Ikegami T, Makino S . The pathogenesis of Rift Valley fever. Viruses. 2011; 3(5):493-519. PMC: 3111045. DOI: 10.3390/v3050493. View

10.

Boyce M, Celma C, Roy P . Bluetongue virus non-structural protein 1 is a positive regulator of viral protein synthesis. Virol J. 2012; 9:178. PMC: 3479040. DOI: 10.1186/1743-422X-9-178. View

11.

Marin-Lopez A, Bermudez R, Calvo-Pinilla E, Moreno S, Brun A, Ortego J . Pathological Characterization Of IFNAR(-/-) Mice Infected With Bluetongue Virus Serotype 4. Int J Biol Sci. 2016; 12(12):1448-1460. PMC: 5166487. DOI: 10.7150/ijbs.14967. View

12.

van Gennip R, Drolet B, Rozo Lopez P, Roost A, Boonstra J, Van Rijn P . Vector competence is strongly affected by a small deletion or point mutations in bluetongue virus. Parasit Vectors. 2019; 12(1):470. PMC: 6790033. DOI: 10.1186/s13071-019-3722-2. View

13.

Drexler I, Staib C, Sutter G . Modified vaccinia virus Ankara as antigen delivery system: how can we best use its potential?. Curr Opin Biotechnol. 2004; 15(6):506-12. PMC: 7127071. DOI: 10.1016/j.copbio.2004.09.001. View

14.

Besselaar T, Blackburn N . The synergistic neutralization of Rift Valley fever virus by monoclonal antibodies to the envelope glycoproteins. Arch Virol. 1992; 125(1-4):239-50. DOI: 10.1007/BF01309641. View

15.

Lorenzo G, Lopez-Gil E, Ortego J, Brun A . Efficacy of different DNA and MVA prime-boost vaccination regimens against a Rift Valley fever virus (RVFV) challenge in sheep 12 weeks following vaccination. Vet Res. 2018; 49(1):21. PMC: 5822472. DOI: 10.1186/s13567-018-0516-z. View

16.

Hartman A . Rift Valley Fever. Clin Lab Med. 2017; 37(2):285-301. PMC: 5458783. DOI: 10.1016/j.cll.2017.01.004. View

17.

Matsuo E, Celma C, Boyce M, Viarouge C, Sailleau C, Dubois E . Generation of replication-defective virus-based vaccines that confer full protection in sheep against virulent bluetongue virus challenge. J Virol. 2011; 85(19):10213-21. PMC: 3196398. DOI: 10.1128/JVI.05412-11. View

18.

Marin-Lopez A, Otero-Romero I, de la Poza F, Menaya-Vargas R, Calvo-Pinilla E, Benavente J . VP2, VP7, and NS1 proteins of bluetongue virus targeted in avian reovirus muNS-Mi microspheres elicit a protective immune response in IFNAR(-/-) mice. Antiviral Res. 2014; 110:42-51. DOI: 10.1016/j.antiviral.2014.07.008. View

19.

Rojas J, Pena L, Martin V, Sevilla N . Ovine and murine T cell epitopes from the non-structural protein 1 (NS1) of bluetongue virus serotype 8 (BTV-8) are shared among viral serotypes. Vet Res. 2014; 45:30. PMC: 3995764. DOI: 10.1186/1297-9716-45-30. View

20.

Mellor P, Boorman J, Baylis M . Culicoides biting midges: their role as arbovirus vectors. Annu Rev Entomol. 2000; 45:307-40. DOI: 10.1146/annurev.ento.45.1.307. View