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Development and evaluation of new generation vaccines against bovine respiratory syncytial virus

Blodörn, Krister (2015). Development and evaluation of new generation vaccines against bovine respiratory syncytial virus. Diss. (sammanfattning/summary) Uppsala : Sveriges lantbruksuniv., Acta Universitatis agriculturae Sueciae, 1652-6880 ; 2015:7
ISBN 978-91-576-8212-3
eISBN 978-91-576-8213-0
[Doctoral thesis]

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Abstract

Bovine respiratory syncytial virus (BRSV) is a major cause of respiratory disease in cattle worldwide. Improved BRSV vaccines are needed, with better efficacy and longer duration of protection, in particular when used in calves with specific maternally derived antibodies (MDA). New generation BRSV vaccines should also be DIVA compliant, and thus allow continued seromonitoring in vaccinated herds, including continuous evaluation of vaccine safety and efficacy.

In this thesis work, classic BRSV immunostimulating complexes (BRSV-ISCOMs) were shown to overcome inhibition by specific MDA, and induce a high level of protection, probably mediated by strong humoral and Th1 type T cell responses.

Characterization of proteins in BRSV-ISCOMs was performed to facilitate future standardization or improvement of BRSV-ISCOMs, and to serve as a basis to design efficient subunit vaccines (SU). SU consisted of recombinant human RSV (HRSV) proteins P, M2-1 and N nanorings with epitopes from BRSV proteins F and G.

Three DIVA-compatible vaccines, all omitting the SH protein, were evaluated: two vaccines formulated using SU, adjuvanted by either Montanide ISA71VG (SUMont) or AbISCO-300 (SUAbis); and ΔSHrBRSV, a live recombinant BRSV with deleted SH gene. The safety, immunogenicity and protective efficacy of SUMont, SUAbis and ΔSHrBRSV were compared in calves with specific MDA in a BRSV infection model with high clinical expression, which was also developed in this thesis work.

Both ΔSHrBRSV and SUMont induced protection against BRSV infection, seemingly by activating different immunological pathways. ΔSHrBRSV induced almost complete clinical and virological protection, which appeared to rely mainly on mucosal IgA and systemic neutralizing antibodies directed against viral surface proteins, and T cell priming in the airways. SUMont induced a good level of protection, which appeared to be mediated by HRSV/BRSV cross-reactive specific T cells. SUAbis induced limited protection from BRSV challenge.

The three vaccines BRSV-ISCOMs, ΔSHrBRSV and SUMont, individually identified as promising vaccine candidates, are described and discussed in this thesis, including possibilities to improve their immunogenicity and protective efficacy, and to further investigate induced immunity and DIVA compliancy.

Authors/Creators:Blodörn, Krister
Title:Development and evaluation of new generation vaccines against bovine respiratory syncytial virus
Series/Journal:Acta Universitatis agriculturae Sueciae (1652-6880)
Year of publishing :2015
Depositing date:27 January 2015
Volume:2015:7
Number of Pages:120
Papers/manuscripts:
NumberReferences
IHägglund, Sara; Hu, Kefei; Vargmar, Karin; Poré, Lesly; Olofson, Ann- Sophie; Blodörn, Krister; Anderson, Jenna; Ahooghalandari, Parvin; Pringle, John; Taylor, Geraldine; and Valarcher, Jean-François (2011). Bovine respiratory syncytial virus ISCOMs-Immunity, protection and safety in young conventional calves. Vaccine 29(47), 8719–8730.
IIHägglund, Sara; Hu, Kefei; Blodörn, Krister; Makabi-Panzu, Boby; Gaillard, Anne-Laure; Ellencrona, Karin; Chevret, Didier; Hellman, Lars; Lövgren Bengtsson, Karin; Riffault, Sabine; Taylor, Geraldine; Valarcher, Jean-François; and Eléouët, Jean-François (2014). Characterization of an experimental vaccine for bovine respiratory syncytial virus. Clinical and vaccine immunology: CVI 21(7), 997–1004.
IIIBlodörn, Krister; Hägglund, Sara; Gavier-Widen, Dolores; Eléouët, Jean- François; Riffault, Sabine; Pringle, John; Taylor, Geraldine; and Valarcher, Jean-François. A bovine respiratory syncytial virus model with high clinical expression in calves with specific passive immunity (submitted manuscript).
IVBlodörn, Krister; Hägglund, Sara; Fix, Jenna; Dubuquoy, Catherine; Makabi-Panzu, Boby; Thom, Michelle; Karlsson, Per; Roque, Jean-Louis; Karlstam, Erika; Pringle, John; Eléouët, Jean-François; Riffault, Sabine; Taylor, Geraldine; and Valarcher, Jean-François (2014). Vaccine Safety and Efficacy Evaluation of a Recombinant Bovine Respiratory Syncytial Virus (BRSV) with Deletion of the SH Gene and Subunit Vaccines Based On Recombinant Human RSV Proteins: N-nanorings, P and M2-1, in Calves with Maternal Antibodies. PLoS One 9(6), e100392.
Place of Publication:Uppsala
Publisher:Department of Clinical Sciences, Swedish University of Agricultural Sciences
ISBN for printed version:978-91-576-8212-3
ISBN for electronic version:978-91-576-8213-0
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 > 3 Medical and Health Sciences > 301 Basic Medicine > Immunology in the medical area
(A) Swedish standard research categories 2011 > 3 Medical and Health Sciences > 302 Clinical Medicine > Infectious Medicine
(A) Swedish standard research categories 2011 > 3 Medical and Health Sciences > 302 Clinical Medicine > Respiratory Medicine and Allergy
(A) Swedish standard research categories 2011 > 4 Agricultural Sciences > 403 Veterinary Science > Clinical Science
Agrovoc terms:bovine respiratory syncytial virus, vaccines, calves, recombinant proteins, vaccine adjuvants, immunostimulants, immunity, immune response, infection, models, safety
Keywords:bovine respiratory syncytial virus, BRSV, vaccine, ISCOM, recombinant protein, modified live virus, DIVA, infection model
URN:NBN:urn:nbn:se:slu:epsilon-e-2320
Permanent URL:
http://urn.kb.se/resolve?urn=urn:nbn:se:slu:epsilon-e-2320
ID Code:11756
Faculty:VH - Faculty of Veterinary Medicine and Animal Science
Department:(VH) > Dept. of Clinical Sciences
External funders:L'Agence Nationale de la Recherche / ANR and Biotechnology and Biological Sciences Research Council / BBSRC and FORMAS and Stiftelsen Lantbruksforskning
Deposited By: Krister Blodorn
Deposited On:27 Jan 2015 11:46
Metadata Last Modified:01 Apr 2015 12:08

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