RESEARCH UPDATES ON MALIGNANT CATARRHAL FEVER Cristina W Cunha, - PowerPoint PPT Presentation

RESEARCH UPDATES ON MALIGNANT CATARRHAL FEVER Cristina W Cunha, DVM, PhD Veterinary Medical Officer Animal Disease Research Unit ARS – USDA - Pullman WA

Malignant Catarrhal Fever (MCF) • MCF-virus group ➢ Ovine herpesvirus 2 (OvHV-2) - carried asymptomatically by sheep - causes a usually fatal disease in OvHV-2 clinically susceptible hosts • Sporadic disease – outbreaks

Malignant Catarrhal Fever (MCF) OvHV-2 reservoir • MCF-virus group ➢ Ovine herpesvirus 2 (OvHV-2) - carried asymptomatically by sheep - causes a usually fatal disease in OvHV-2 clinically susceptible hosts clinically susceptible hosts MCF • Sporadic disease – outbreaks

OvHV-2 Infection / MCF Development OvHV-2 inoculum (genome copy number) 10 2 10 3 10 4 10 5 10 6 10 7 10 8 10 9 Sheep neg pos pos pos pos pos pos MCF Cattle neg pos pos MCF Pigs neg pos MCF pos Rabbits neg MCF MCF Pos Bison neg MCF MCF neg = OvHV-2 uninfected pos = OvHV-2 infected MCF = disease Li et al., 2005; Taus et al., 2005; Taus et al., 2006; O’Toole et al., 2007; Gailbreath et al. , 2009; Li et al. , 2012

MCF Prevention and Control 0.4 % • No vaccine or treatment available 6.1 % • Management control strategies ➢ Separation of clinically susceptible 17.5 5 % and carrier hosts ➢ Production of virus-free carriers Li et al. , 2008

Vaccine Strategy ➢ Stimulate a neutralizing antibody response capable of blocking the virus at the entry site, preventing infection and/or disease

Vaccine Development Target Selection  Viral proteins capable of inducing a In vitro assessment protective response Vaccine System Development Expression system Animal challenge Delivery (route, dose, etc.) selection and evaluation experiments Technology Transfer Regulatory Scale-up production Distribution documentation

Genetic immunization Target Selection Anti-gB, gH, gL OvHV-2 antibodies lethal dose ➢ There is no culture system to grow OvHV-2 gB gH/gL MCF Virus Infection Sub clinical neutralization infection outcome No infection ➢ Antibodies anti-OvHV-2 gB, gH and gL can block the virus and prevent MCF Li et al. , 2013; Cunha et al., 2015; Cunha et al., 2016; Cunha et al., 2017

Vaccine Delivery, Efficacy, Safety • Delivery system • Vaccine challenge experiments ➢ Development of a recombinant BoHV-4 expressing the OvHV-2 vaccine targets

MCF Viruses in Domestic and Bighorn Sheep AlHV-1 AlHV-2 AlHV-2-like CpHV-2 Ibex-MCFV OvHV-2-like (big horn sheep) 86% identity OvHV-2 (domestic sheep) CpHV-3

Research group • Hong Li, USDA (Hong.Li@ars.usda.gov) • Cristina Cunha, USDA (Cristina.Cunha@ars.usda.gov) • Donald Knowles, WSU Palouse Region, Washington • Naomi Taus, USDA • Margaret Highland, USDA Washington State University, Pullman WA • Donal O’Toole, U. of Wyoming • Gaetano Donofrio, U. of Parma, Italy • Anthony Nicola, WSU Animal Disease Research Facility, Pullman WA

MCF in sheep – diagnostic tools • Quantitative PCR • In situ hybridization Arteritis in sheep OvHV-2 probe OvHV-2 genome copies Health Group Status Intestine Lung Kidney Liver Total MCF Lamb 457,000 433,000 283,000 51,500 306,000 Cohort lambs 3,870 4,050 330 730 2,240 Clinically Lambs 570 210 10 40 210 Normal Adults 430 30 20 35 130 Pesavento et al. , in preparation Phillips et al. , 2018