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An efficacious vaccine for sheep-associated malignant catarrhal fever (SA-MCF) is important for the livestock industry. Research towards SA-MCF vaccine development is hindered by the absence of culture systems to propagate the causative agent, ovine herpesvirus-2 (OvHV-2), which means its genome cannot be experimentally modified to generate an attenuated vaccine strain. Alternative approaches for vaccine development are needed to deliver OvHV-2 antigens. Bovine herpesvirus 4 (BoHV-4) has been evaluated as a vaccine vector for several viral antigens with promising results. In this study, we genetically engineered BoHV-4 to express OvHV-2 glycoprotein B (gB) and evaluated its efficacy as an SA-MCF vaccine using a rabbit model. The construction of a viable recombinant virus (BoHV-4-AΔTK-OvHV-2-gB) and confirmation of OvHV-2 gB expression were performed in vitro. The immunization of rabbits with BoHV-4-AΔTK-OvHV-2-gB elicited strong humoral responses to OvHV-2 gB, including neutralizing antibodies. Following intra-nasal challenge with a lethal dose of OvHV-2, 42.9% of the OvHV-2 gB vaccinated rabbits were protected against SA-MCF, while all rabbits in the mock-vaccinated group succumbed to SA-MCF. Overall, OvHV-2 gB delivered by the recombinant BoHV-4 was immunogenic and partly protective against SA-MCF in rabbits. These are promising results towards an SA-MCF vaccine; however, improvements are needed to increase protection rates.
Smriti Shringi; Donal O’Toole; Emily Cole; Katherine Baker; Stephen White; Gaetano Donofrio; Hong Li; Cristina Cunha. OvHV-2 Glycoprotein B Delivered by a Recombinant BoHV-4 Is Immunogenic and Induces Partial Protection against Sheep-Associated Malignant Catarrhal Fever in a Rabbit Model. Vaccines 2021, 9, 90 .
AMA StyleSmriti Shringi, Donal O’Toole, Emily Cole, Katherine Baker, Stephen White, Gaetano Donofrio, Hong Li, Cristina Cunha. OvHV-2 Glycoprotein B Delivered by a Recombinant BoHV-4 Is Immunogenic and Induces Partial Protection against Sheep-Associated Malignant Catarrhal Fever in a Rabbit Model. Vaccines. 2021; 9 (2):90.
Chicago/Turabian StyleSmriti Shringi; Donal O’Toole; Emily Cole; Katherine Baker; Stephen White; Gaetano Donofrio; Hong Li; Cristina Cunha. 2021. "OvHV-2 Glycoprotein B Delivered by a Recombinant BoHV-4 Is Immunogenic and Induces Partial Protection against Sheep-Associated Malignant Catarrhal Fever in a Rabbit Model." Vaccines 9, no. 2: 90.
Escherichia coli O157:H7 is the predominant cause of diarrhea-associated hemolytic uremic syndrome (HUS) worldwide. Its cardinal virulence traits are Shiga toxins, which are encoded by stx genes, the most common of which are stx1a, stx2a, and stx2c. The toxins these genes encode differ in their in vitro and experimental phenotypes, but the human population-level impact of these differences is poorly understood. Using Shiga toxin-encoding bacteriophage insertion typing and real-time polymerase chain reaction, we genotyped isolates from 936 E. coli O157:H7 cases and verified HUS status via chart review. We compared the HUS risk between isolates with stx2a and those with stx2a and another gene and estimated additive interaction of the stx genes. Adjusted for age and symptoms, the HUS incidence of E. coli O157:H7 containing stx2a alone was 4.4% greater (95% confidence interval (CI) -0.3%, 9.1%) than when it occurred with stx1a. When stx1a and stx2a occur together, the risk of HUS was 27.1% lower (95% CI -87.8%, -2.3%) than would be expected if interaction were not present. At the population level, temporal or geographic shifts toward these genotypes should be monitored, and stx genotype may be an important consideration in clinically predicting HUS among E. coli O157:H7 cases.
Gillian A.M. Tarr; Taryn Stokowski; Smriti Shringi; Phillip I. Tarr; Stephen B. Freedman; Hanna N. Oltean; Peter M. Rabinowitz; Linda Chui. Contribution and Interaction of Shiga Toxin Genes to Escherichia coli O157:H7 Virulence. Toxins 2019, 11, 607 .
AMA StyleGillian A.M. Tarr, Taryn Stokowski, Smriti Shringi, Phillip I. Tarr, Stephen B. Freedman, Hanna N. Oltean, Peter M. Rabinowitz, Linda Chui. Contribution and Interaction of Shiga Toxin Genes to Escherichia coli O157:H7 Virulence. Toxins. 2019; 11 (10):607.
Chicago/Turabian StyleGillian A.M. Tarr; Taryn Stokowski; Smriti Shringi; Phillip I. Tarr; Stephen B. Freedman; Hanna N. Oltean; Peter M. Rabinowitz; Linda Chui. 2019. "Contribution and Interaction of Shiga Toxin Genes to Escherichia coli O157:H7 Virulence." Toxins 11, no. 10: 607.