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Development and evaluation of a subunit DIVA vaccine against bluetongue virus serotype 8 in cattle

Anderson, Jenna (2014). Development and evaluation of a subunit DIVA vaccine against bluetongue virus serotype 8 in cattle. Diss. (sammanfattning/summary) Uppsala : Sveriges lantbruksuniv., Acta Universitatis agriculturae Sueciae, 1652-6880 ; 2014:48
ISBN 978-91-576-8044-0
eISBN 978-91-576-8045-7
[Doctoral thesis]

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Abstract

Bluetongue virus (BTV) causes the primarily vector-borne bluetongue disease of ruminants, which poses a permanent threat to Europe since new serotypes and strains are frequently introduced. Vaccination of cattle is essential to control BTV outbreaks. Commercial attenuated and inactivated vaccines are efficacious in reducing BTV spread and disease, but do not fulfil all safety, adaptability, or production requirements. Additionally, no current vaccines allow the differentiation of infected from vaccinated animals (DIVA). DIVA vaccines enable surveillance of BTV epidemiology and vaccine efficacy, and facilitate a quick return for countries to a BTV-free status. This thesis presents the development and evaluation of a novel subunit DIVA vaccine against BTV serotype 8 (BTV-8) in cattle.

Five His-tagged recombinant BTV proteins (VP2, VP5 of BTV-8; NS1, NS2, NS3 of BTV-2) were produced in baculovirus or E. coli expression systems. Purification protocols were optimized for all but VP5. Based on the feasibility of protein production and the capability of the remaining four proteins to induce humoral or cellular immune responses in mice, VP2, NS1, and NS2 were selected to formulate an experimental vaccine combined to an ISCOM-matrix adjuvant (SubV).

Next, cattle were immunized twice at a three-week interval with SubV, a commercial inactivated vaccine, or a placebo. SubV induced humoral immune responses, including virus-neutralizing antibodies, against all three proteins, as well as a cellular immune response directed against NS1. These responses were of similar type and comparable magnitude between both vaccines, suggesting that SubV might provide protection that is at least as effective as the commercial vaccine. Finally, the protective efficacy of SubV was evaluated and complete virological and clinical protection against virulent BTV-8 challenge was observed following vaccination in calves. This was likely due to the induction of virus-neutralizing antibodies directed against VP2 of BTV-8 and cross-serotype T cell responses directed against NS1 and NS2 of BTV-2. Furthermore, SubV was shown to be DIVA-compliant based on the detection of antibodies directed against VP7, by using commercially-available diagnostic assays. This novel BTV subunit vaccine is a promising candidate and should be further developed.

Authors/Creators:Anderson, Jenna
Title:Development and evaluation of a subunit DIVA vaccine against bluetongue virus serotype 8 in cattle
Series/Journal:Acta Universitatis agriculturae Sueciae (1652-6880)
Year of publishing :2014
Volume:2014:48
Number of Pages:123
Papers/manuscripts:
NumberReferences
I.Anderson, Jenna; Bréard, Emmanuel; Lövgren Bengtsson, Karin; Grönvik, Kjell-Olov; Zientara, Stéphan; Valarcher, Jean-François; and Sara Hägglund (2014). Purification, stability, and immunogenicity analyses of five bluetongue virus proteins for use in the development of a subunit vaccine that allows the differentiation of infected from vaccinated animals. Clinical and Vaccine Immunology 21(3), 443-452.
II.Anderson, Jenna; Hägglund, Sara; Bréard, Emmanuel; Lövgren Bengtsson, Karin; Pringle, John; Zientara, Stéphan; and Jean-François Valarcher (2013). Evaluation of the immunogenicity of an experimental subunit vaccine that allows differentiation between infected and vaccinated animals against bluetongue virus serotype 8 in cattle. Clinical and Vaccine Immunology 20(8), 1115-1122.
III.Anderson, Jenna; Hägglund, Sara; Bréard, Emmanuel; Riou, Mickaël; Zohari, Siamak; Comtet, Loic; Olofson, Ann-Sophie; Gélineau, Robert; Martin, Guillaume; Elvander, Marianne; Blomqvist, Gunilla; Zientara, Stéphan; and Jean-François Valarcher. Strong protection induced by an experimental DIVA subunit vaccine against bluetongue virus serotype 8 in cattle (submitted manuscript).
Place of Publication:Uppsala
Publisher:Sveriges lantbruksuniversitet, Institutionen för kliniska vetenskaper
ISBN for printed version:978-91-576-8044-0
ISBN for electronic version:978-91-576-8045-7
ISSN:1652-6880
Language:English
Publication Type:Doctoral thesis
Full Text Status:Public
Agris subject categories.:L Animal production > L73 Animal diseases
Subjects:(A) Swedish standard research categories 2011 > 1 Natural sciences > 106 Biological Sciences (Medical to be 3 and Agricultural to be 4) > Cell Biology
(A) Swedish standard research categories 2011 > 1 Natural sciences > 106 Biological Sciences (Medical to be 3 and Agricultural to be 4) > Immunology (Immunology in the medical area to be 30110)
(A) Swedish standard research categories 2011 > 1 Natural sciences > 106 Biological Sciences (Medical to be 3 and Agricultural to be 4) > Microbiology (Microbiology in the medical area to be 30109)
(A) Swedish standard research categories 2011 > 2 Engineering and Technology > 206 Medical Engineering > Medical Laboratory and Measurements Technologies
(A) Swedish standard research categories 2011 > 3 Medical and Health Sciences > 301 Basic Medicine > Cell and Molecular Biology
(A) Swedish standard research categories 2011 > 3 Medical and Health Sciences > 301 Basic Medicine > Immunology in the medical area
(A) Swedish standard research categories 2011 > 4 Agricultural Sciences > 403 Veterinary Science > Medical Bioscience
(A) Swedish standard research categories 2011 > 4 Agricultural Sciences > 403 Veterinary Science > Clinical Science
Agrovoc terms:bluetongue, bluetongue virus, animal diseases, cattle, vaccines, vaccination, immunological techniques, serotypes
Keywords:bluetongue, virus, cattle, vaccine, subunit, immunogenicity, humoral, cellular, protection, DIVA
URN:NBN:urn:nbn:se:slu:epsilon-e-2058
Permanent URL:
http://urn.kb.se/resolve?urn=urn:nbn:se:slu:epsilon-e-2058
ID Code:11406
Faculty:VH - Faculty of Veterinary Medicine and Animal Science
Department:(VH) > Dept. of Clinical Sciences
External funders:EU FP7 and FORMAS and Stiftelsen Lantbruksforskning
Deposited By: Jenna Anderson
Deposited On:19 Aug 2014 10:51
Metadata Last Modified:02 Dec 2014 11:07

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