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

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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)


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RESEARCH UPDATES ON MALIGNANT CATARRHAL FEVER

Cristina W Cunha, DVM, PhD Veterinary Medical Officer Animal Disease Research Unit ARS – USDA - Pullman WA

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Malignant Catarrhal Fever (MCF)

OvHV-2

  • MCF-virus group

➢ Ovine herpesvirus 2 (OvHV-2)

  • carried asymptomatically by sheep
  • causes a usually fatal disease in

clinically susceptible hosts

  • Sporadic disease – outbreaks
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Malignant Catarrhal Fever (MCF)

  • MCF-virus group

➢ Ovine herpesvirus 2 (OvHV-2)

  • carried asymptomatically by sheep
  • causes a usually fatal disease in

clinically susceptible hosts

  • Sporadic disease – outbreaks

OvHV-2 reservoir OvHV-2 clinically susceptible hosts MCF

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OvHV-2 Infection / MCF Development

neg = OvHV-2 uninfected pos = OvHV-2 infected MCF = disease

102 103 104 105 106 107 108 109 Sheep neg pos pos pos pos pos pos MCF Cattle neg pos pos MCF Pigs neg pos MCF Rabbits neg pos MCF MCF Bison neg Pos MCF MCF OvHV-2 inoculum (genome copy number)

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

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MCF Prevention and Control

  • No vaccine or treatment available
  • Management control strategies

➢ Separation of clinically susceptible

and carrier hosts

➢ Production of virus-free carriers

0.4 % 6.1 % 17.5 5 %

Li et al., 2008

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Vaccine Strategy

➢ Stimulate a neutralizing antibody response capable of blocking

the virus at the entry site, preventing infection and/or disease

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Vaccine Development

Technology Transfer

Regulatory documentation Scale-up production Distribution

Vaccine System Development

Expression system selection and evaluation Delivery (route, dose, etc.) Animal challenge experiments

Target Selection

Viral proteins capable of inducing a protective response In vitro assessment

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Target Selection

➢ Antibodies anti-OvHV-2 gB, gH and gL

can block the virus and prevent MCF ➢ There is no culture system to grow OvHV-2

gB gH/gL

Li et al. , 2013; Cunha et al., 2015; Cunha et al., 2016; Cunha et al., 2017

OvHV-2 lethal dose Anti-gB, gH, gL antibodies Genetic immunization Infection

  • utcome

MCF Sub clinical infection

Virus neutralization

No infection

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Vaccine Delivery, Efficacy, Safety

  • Delivery system

➢ Development of a recombinant BoHV-4

expressing the OvHV-2 vaccine targets

  • Vaccine challenge experiments
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MCF Viruses in Domestic and Bighorn Sheep

AlHV-1 AlHV-2 AlHV-2-like CpHV-2 Ibex-MCFV

OvHV-2-like (big horn sheep) OvHV-2 (domestic sheep)

CpHV-3

86% identity

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Research group

  • Hong Li, USDA (Hong.Li@ars.usda.gov)
  • Cristina Cunha, USDA (Cristina.Cunha@ars.usda.gov)
  • Donald Knowles, WSU
  • Naomi Taus, USDA
  • Margaret Highland, USDA
  • Donal O’Toole, U. of Wyoming
  • Gaetano Donofrio, U. of Parma, Italy
  • Anthony Nicola, WSU

Washington State University, Pullman WA Animal Disease Research Facility, Pullman WA Palouse Region, Washington

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MCF in sheep – diagnostic tools

  • Quantitative PCR

OvHV-2 probe Arteritis in sheep

  • In situ hybridization

Health Status Group OvHV-2 genome copies Intestine Lung Kidney Liver Total MCF Lamb 457,000 433,000 283,000 51,500 306,000 Clinically Normal Cohort lambs 3,870 4,050 330 730 2,240 Lambs 570 210 10 40 210 Adults 430 30 20 35 130

Phillips et al. , 2018 Pesavento et al. , in preparation