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ARS Home » Pacific West Area » Pullman, Washington » Animal Disease Research » Research » Research Project #441300

Research Project: Development of a Vaccine and Improved Diagnostics for Malignant Catarrhal Fever

Location: Animal Disease Research

Project Number: 2090-32000-045-000-D
Project Type: In-House Appropriated

Start Date: Oct 1, 2021
End Date: Sep 30, 2026

Malignant catarrhal fever (MCF) is an often-fatal viral disease that affects primarily ruminants. The disease is caused by gamma herpesviruses in the MCF group of the Macavirus genus. These viruses are carried asymptomatically by certain animal species that serves as virus reservoirs but can cause disease when transmitted to other non-adapted, susceptible species. Ovine herpesvirus-2 (OvHV-2), transmitted by sheep, is globally distributed and the most frequent cause of MCF worldwide. In North America, sheep-associated MCF is a leading cause of death in American bison, which are highly susceptible to the disease. Overall, MCF results in significant economic impact to agriculture not only due to the loss of animals but also because it imposes restrictions to multispecies operations. With no treatment or vaccines available, currently the only way to control the disease is separating carrier and susceptible animals. Therefore, availability of an effective vaccine to MCF and reliable diagnostic assays are top priorities for the agricultural industry. Using rabbits as a laboratory animal model, we have recently demonstrated that protection to MCF can be achieved when using recombinant viral vectors carrying OvHV-2 genes as potential vaccines. In this project we propose to test the safety, efficacy, and duration of protection of selected vaccine candidates in relevant livestock species. We also plan to improve disease control by developing a point-of-care serological assay for detection of MCF virus reservoirs. Objective 1: Assess the safety and efficacy of new MCF vaccine platforms and delivery systems. Sub-objective 1.A: Evaluate the safety of immunogen formulations to deliver OvHV-2 gB as an SA-MCF vaccine in cattle and bison. Sub-objective 1.B: Determine the efficacy of a vaccine targeting OvHV-2 gB in preventing SA-MCF in bison. Sub-objective 1.C: Assess the risk of SA-MCF vaccinated bison to develop MCF upon exposure to OvHV-2 infected sheep. Objective 2: Improve MCF diagnosis by developing new optimized diagnostic assays.

This project focuses on two important aspects of malignant catarrhal fever (MCF) research: Objective 1 is development of a safe and effective sheep-associated (SA)-MCF vaccine for clinically susceptible species and Objective 2 is improvement of diagnostic capabilities for detection of MCF virus reservoirs. In Sub-objective 1.A, we will test a recombinant viral vectored vaccine expressing ovine herpesvirus-2 (OvHV-2) glycoprotein B (gB) in cattle and bison to determine its safety and immunogenicity. Vaccination will be done with the viral vector in adjuvant alone or following prime immunization with DNA encoding OvHV-2 gB. Experimental animals will be monitored for potential adverse effects from immunizations and development of immune responses to the OvHV-2 antigen. Our hypothesis is that immunization with the vaccine formulations and regimes tested does not cause adverse reactions in cattle or bison. In Sub-objective 1.B, we will determine the efficacy of a vaccine in preventing SA-MCF in bison. The hypothesis for this sub-objective is that immunization with a vaccine targeting OvHV-2 gB protects bison from SA-MCF following challenge with a lethal dose of OvHV-2. Experimental animals will be challenged at different times post-vaccination to evaluate the duration of protection induced by vaccination. In Sub-objective 1.C, we will assess the risk of SA-MCF vaccinated bison to develop MCF upon exposure to OvHV-2 infected sheep. This will be a field trial to test the hypothesis that bison immunized with the SA-MCF vaccine have reduced risk of developing MCF than non-vaccinated animals when exposed to OvHV-2 infected sheep. Vaccinated and non-vaccinated control bison will be exposed to a flock of OvHV-2 infected sheep maintained at close proximity for at least 3 months. Development of disease in both groups will be used to calculate protection rates and risks. In Objective 2 we will improve MCF diagnosis by developing a point-of-care serological assay for detection of MCFV antibodies. The goal is to validate and optimize a lateral flow immunoassay using recombinant OvHV-2 gB coupled to quantum dots as antigen. This is expected to result in a rapid, simple, sensitive, and inexpensive method to identify infected animals that can serve as viral reservoirs.