A protective bivalent vaccine against Rift Valley fever and bluetongue

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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.

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Rift Valley fever epidemic in Saudi Arabia: epidemiological, clinical, and laboratory characteristics.

Tariq Madani, Yagob Al-Mazrou, Mohammad Al-Jeffri … (2003)

This cohort descriptive study summarizes the epidemiological, clinical, and laboratory characteristics of the Rift Valley fever (RVF) epidemic that occurred in Saudi Arabia from 26 August 2000 through 22 September 2001. A total of 886 cases were reported. Of 834 reported cases for which laboratory results were available, 81.9% were laboratory confirmed, of which 51.1% were positive for only RVF immunoglobulin M, 35.7% were positive for only RVF antigen, and 13.2% were positive for both. The mean age (+/- standard deviation) was 46.9+/-19.4 years, and the ratio of male to female patients was 4:1. Clinical and laboratory features included fever (92.6% of patients), nausea (59.4%), vomiting (52.6%), abdominal pain (38.0%), diarrhea (22.1%), jaundice (18.1%), neurological manifestations (17.1%), hemorrhagic manifestations (7.1%), vision loss or scotomas (1.5%), elevated liver enzyme levels (98%), elevated lactate dehydrogenase level (60.2%), thrombocytopenia (38.4%), leukopenia (39.7%), renal impairment or failure (27.8%), elevated creatine kinase level (27.3%), and severe anemia (15.1%). The mortality rate was 13.9%. Bleeding, neurological manifestations, and jaundice were independently associated with a high mortality rate. Patients with leukopenia had significantly a lower mortality rate than did those with a normal or high leukocyte count (2.3% vs. 27.9%; odds ratio, 0.09; 95% confidence interval, 0.01-0.63).

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The pathology and pathogenesis of bluetongue.

N.J. Maclachlan, C.P. Drew, K.E. Darpel … (2009)

Bluetongue (BT) is an insect-transmitted viral disease of wild and domestic ruminants and, occasionally, other species. Amongst domestic livestock, BT is most common in certain breeds of sheep whereas asymptomatic BT virus (BTV) infection of cattle is typical in enzootic regions. BT in cattle can be a feature of specific outbreaks, notably the current epizootic in Europe caused by BTV serotype 8. BTV replicates within mononuclear phagocytic and endothelial cells, lymphocytes and possibly other cell types in lymphoid tissues, the lungs, skin and other tissues. Infected ruminants may exhibit a prolonged but not persistent viraemia and BTV is associated with erythrocytes during the late stages of this prolonged viraemia. The pathogenesis of BT involves injury to small blood vessels in target tissues, but the relative contributions of direct virus-induced cytolysis and virus-induced vasoactive mediators in causing endothelial injury and dysfunction are presently unclear. The lesions of BT are characteristic and include: haemorrhage and ulcers in the oral cavity and upper gastrointestinal tract; necrosis of skeletal and cardiac muscle; coronitis; subintimal haemorrhage in the pulmonary artery; oedema of the lungs, ventral subcutis, and fascia of the muscles of the neck and abdominal wall; and pericardial, pleural and abdominal effusions. Transplacental transmission of BTV in ruminants, with subsequent fetal infection, is a property of specific virus strains, especially those propagated in embryonated eggs or cell culture. The outcome of BTV infection of fetal ruminants is age-dependent, with distinctive cavitating lesions of the central nervous system in animals that survive infection in early gestation. Immune competence to BTV arises by mid-gestation, and animals infected in late gestation can be born viraemic and without significant brain malformations.

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Compact, synthetic, vaccinia virus early/late promoter for protein expression.

Richard Moss, Kalyan S. Chakrabarti, J Sisler (1997)

Vaccinia virus, a member of the poxvirus family, is widely used as a mammalian cell expression vector. Vaccinia virus replicates in the cytoplasm and has its own transcriptional system, making it necessary to use viral promoters. Here, we describe the design, construction and use of a 40-bp synthetic, vaccinia virus promoter with largely overlapping early and late regulatory elements. Convenient plasmid transfer vectors are depicted for expression of one or two genes under control of strong early/late promoters and allowing for thymidine kinase (TK) or antibiotic selection of recombinant viruses.

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Author and article information

Contributors

Alejandro Brun:

ORCID: http://orcid.org/0000-0001-7865-538X

brun@inia.es

Javier Ortego:

ORCID: http://orcid.org/0000-0002-4275-7277

ortego@inia.es

Journal

Journal ID (nlm-ta): NPJ Vaccines

Journal ID (iso-abbrev): NPJ Vaccines

Title: NPJ Vaccines

Publisher: Nature Publishing Group UK (London )

ISSN (Electronic): 2059-0105

Publication date (Electronic): 30 July 2020

Publication date PMC-release: 30 July 2020

Publication date Collection: 2020

Volume: 5

Electronic Location Identifier: 70

Affiliations

[1 ]GRID grid.419190.4, ISNI 0000 0001 2300 669X, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria, , Centro de Investigación en Sanidad Animal (INIA-CISA), ; Madrid, Spain

[2 ]GRID grid.47100.32, ISNI 0000000419368710, Section of Infectious Diseases, Department of Internal Medicine, , Yale University School of Medicine, ; New Haven, CT USA

[3 ]GRID grid.507631.6, ISNI 0000 0004 1761 1940, Instituto de Ganadería de Montaña (CSIC-Universidad de León), ; León, Spain

[4 ]GRID grid.419190.4, ISNI 0000 0001 2300 669X, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria, Departamento de Biotecnología, ; Madrid, Spain

Author information

Luis Jiménez-Cabello http://orcid.org/0000-0001-8085-5823

Alejandro Brun http://orcid.org/0000-0001-7865-538X

Javier Ortego http://orcid.org/0000-0002-4275-7277

Article

Publisher ID: 218

DOI: 10.1038/s41541-020-00218-y

PMC ID: 7393076

PubMed ID: 32793399

SO-VID: 7010a0b6-25e6-4e82-ba8f-c4747df2daf1

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 2 April 2020

Date accepted : 6 July 2020

Funding

Funded by: FundRef https://doi.org/10.13039/100010686, EC | EU Framework Programme for Research and Innovation H2020 | H2020 European Institute of Innovation and Technology (H2020 The European Institute of Innovation and Technology);

Award ID: NO.727393-PALE-Blu

Award Recipient : Eva Calvo-Pinilla Javier Ortego

Funded by: FundRef https://doi.org/10.13039/501100011033, Ministry of Economy and Competitiveness | Agencia Estatal de Investigación (Spanish Agencia Estatal de Investigación);

Award ID: AGL-2014-57430R

Award ID: AGL2017-83226R

Award ID: AGL2017-82570-R

Award Recipient : Javier Ortego

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Keywords: biotechnology,immunology,microbiology

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Keywords: biotechnology, immunology, microbiology

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A protective bivalent vaccine against Rift Valley fever and bluetongue

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European Journal of Microbiology and Immunology

Most cited references 60

Rift Valley fever epidemic in Saudi Arabia: epidemiological, clinical, and laboratory characteristics.

The pathology and pathogenesis of bluetongue.

Compact, synthetic, vaccinia virus early/late promoter for protein expression.

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Cited by 14

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