| 1. |
- Blodörn, Krister, et al.
(författare)
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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
- 2014
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9, s. 1-17
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Tidskriftsartikel (refereegranskat)abstract
- The development of safe and effective vaccines against both bovine and human respiratory syncytial viruses (BRSV, HRSV) to be used in the presence of RSV-specific maternally-derived antibodies (MDA) remains a high priority in human and veterinary medicine. Herein, we present safety and efficacy results from a virulent BRSV challenge of calves with MDA, which were immunized with one of three vaccine candidates that allow serological differentiation of infected from vaccinated animals (DIVA): an SH gene-deleted recombinant BRSV (Delta SHrBRSV), and two subunit (SU) formulations based on HRSV-P, -M2- 1, and -N recombinant proteins displaying BRSV-F and -G epitopes, adjuvanted by either oil emulsion (Montanide ISA71(VG), SUMont) or immunostimulating complex matrices (AbISCO-300, SUAbis). Whereas all control animals developed severe respiratory disease and shed high levels of virus following BRSV challenge, Delta SHrBRSV-immunized calves demonstrated almost complete clinical and virological protection five weeks after a single intranasal vaccination. Although mucosal vaccination with DSHrBRSV failed to induce a detectable immunological response, there was a rapid and strong anamnestic mucosal BRSV-specific IgA, virus neutralizing antibody and local T cell response following challenge with virulent BRSV. Calves immunized twice intramuscularly, three weeks apart with SUMont were also well protected two weeks after boost. The protection was not as pronounced as that in Delta SHrBRSV-immunized animals, but superior to those immunized twice subcutaneously three weeks apart with SUAbis. Antibody responses induced by the subunit vaccines were non-neutralizing and not directed against BRSV F or G proteins. When formulated as SUMont but not as SUAbis, the HRSV N, P and M2-1 proteins induced strong systemic cross-protective cell-mediated immune responses detectable already after priming. Delta SHrBRSV and SUMont are two promising DIVA-compatible vaccines, apparently inducing protection by different immune responses that were influenced by vaccine-composition, immunization route and regimen.
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| 2. |
- Hägglund, Sara, et al.
(författare)
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Characterization of an Experimental Vaccine for Bovine Respiratory Syncytial Virus
- 2014
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Ingår i: Clinical and Vaccine Immunology. - 1556-6811 .- 1556-679X. ; 21:7, s. 997-1004
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Tidskriftsartikel (refereegranskat)abstract
- Bovine respiratory syncytial virus (BRSV) and human respiratory syncytial virus (HRSV) are major causes of respiratory disease in calves and children, respectively, and are priorities for vaccine development. We previously demonstrated that an experimental vaccine, BRSV-immunostimulating complex (ISCOM), is effective in calves with maternal antibodies. The present study focuses on the antigenic characterization of this vaccine for the design of new-generation subunit vaccines. The results of our study confirmed the presence of membrane glycoprotein (G), fusion glycoprotein (F), and nucleoprotein (N) proteins in the ISCOMs, and this knowledge was extended by the identification of matrix (M), M2-1, phosphoprotein (P), small hydrophobic protein (SH) and of cellular membrane proteins, such as the integrins alpha(V)beta(1), alpha(V)beta(3), and alpha(3)beta(1). The quantity of the major protein F was 4- to 5-fold greater than that of N (similar to 77 mu g versus similar to 17 mu g/calf dose), whereas G, M, M2-1, P, and SH were likely present in smaller amounts. The polymerase (L), M2-2, nonstructural 1 (NS1), and NS2 proteins were not detected, suggesting that they are not essential for protection. Sera from the BRSV-ISCOM-immunized calves contained high titers of IgG antibody specific for F, G, N, and SH. Antibody responses against M and P were not detected; however, this does not exclude their role in protective T-cell responses. The absence of immunopathological effects of the cellular proteins, such as integrins, needs to be further confirmed, and their possible contribution to adjuvant functions requires elucidation. This work suggests that a combination of several surface and internal proteins should be included in subunit RSV vaccines and identifies absent proteins as potential candidates for differentiating infected from vaccinated animals.
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| 3. |
- Hägglund, Sara, et al.
(författare)
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Kinetics and antibody isotype profile in calves intranasally primed with BRSV Delta SH: effects of parenteral boosting with human (H)RSV proteins and implications in protection against BRSV
- 2014
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Ingår i: Immunology. - 0019-2805 .- 1365-2567. ; 143, s. 77-77
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- BRSV, which is a major cause of respiratory disease in young calves, is closely related to HRSV, the most important cause of respiratory disease in young infants. There are no commercially available HRSV vaccines and BRSV vaccines are poorly effective in calves with maternal antibodies. We have investigated the kinetics of the BRSV-specific B-cell responses in calves with maternally derived antibodies (MDA) following intranasal (i.n.) priming with BRSV lacking the SH gene (BRSV∆SH), and intramuscular (i.m.) boosting with a protein-based subunit vaccine consisting of recombinant HRSV proteins: N nanorings, P and M1-2, in Montanide ISA 71 adjuvant (SUMONT), in relation to protection. Following i.n. vaccination with ∆SH BRSV, calves did not develop a detectable local or systemic antibody response, or detectable circulating BRSV-specific plasma cells. However, following i.m. boosting with SUMONT, there was a strong production of all antibody isotypes in serum and nasal secretions, with detectable circulating BRSV-specific plasma cells. Following challenge with wild-type BRSV, all vaccinated calves developed a rapid secondary mucosal and serum antibody response. A rapid increase in serum neutralising antibodies was detected in all groups of vaccinated calves excepted for some calves primed i.n. with ∆SH BRSV on two occasions. All vaccination regimes induced some protection against BRSV challenge. However, protection did not appear to correlate with induction of neutralising antibodies.
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