JCODr. Javier Castillo-Olivares

Name: Javier Castillo-Olivares

Address:The Pirbright Institute, Pirbright, Ash Road,Pirbright, Woking Surrey GU24 ONF

Telephone: +44 1483 232441 (direct: 231081)
Fax: +44 1483 232448

Degrees:

1991 - Licenciado en Veterinaria (equivalent to B Vet Sc), University of Madrid

1992 - Master en Microbiologia Farmaceutica Industrial (equivalent to MSc Pharmaceutical Industrial Microbiology), University of Madrid.

2004 - PhD, Open University / Animal Health Trust

Positions held:

2012 - ……   Present Position:– African horse sickness

Vector-borne Diseases Programme, The Pirbright Institute

2009 – 2012 Senior Post-Doctoral Scientist, Orbivirus Molecular Research, Institute for Animal Health, Pirbright
2007 - 2009 Senior Post-Doctoral Scientist, FMD Vaccine Differentiation, Institute for Animal Health
2004 - 2007 Senior Post-Doctoral Scientist, Equine Virology, Animal Health Trust
1998 – 2004 Veterinary Virologist, Equine Virology, Animal Health Trust / Part-Time PhD student
1994 – 1998 Veterinary Virologist, Equine Virology, Animal Health Trust
1992 - 1993 Microbiology Quality Control Scientific Officer

Synopsis of Research career and relevant expertise:

I am a veterinary virologist with a keen interest and expertise in pathogenesis, diagnostics and control of RNA virus infections of mammals, especially horses.
After obtaining my veterinary degree, I completed an MSc course on Pharmaceutical Industrial Microbiology and joined the department of Microbiology at the Instituto Llorente S.A.in Madrid as a Scientific Officer working in the microbiological control of pharmaceutical products and sterile areas.
I moved to the UK in 1994 after registering in the Royal College of Veterinary Surgeons and joined the Diagnostic Virology Department of the Animal Health Trust as a veterinarian responsible for the production of diagnostic antigens and equine reference antisera (for equine influenza, equine herpesvirus and equine viral arteritis). I also was responsible for the supervision of diagnostic tests and development of novel diagnostic virology techniques. During this period I set up PCR based diagnostics for equine herpesvirus abortion and participated in the development of an antibody capture ELISA for Equine Viral Arteritis (EAV) and in an international programme for the harmonisation of diagnostic techniques for EAV. Soon after joining the AHT, I obtained a Home Office Personal Licence to work with experimental animals under the ‘Animals (Scientific Procedures) Act’ and began to work designing protocols and performing experiments in vivo to test the efficacy of equine viral vaccines.


Equine viral arteritis research

Involvement in the evaluation of a prototype vaccine for EAV stimulated my interest for immune responses to viral infections and completed a PhD studying the effector mechanisms of the adaptive immune response against EAV and how these can be induced efficiently by novel ‘marker’ vaccines. During this period, a challenge model to study EAV in the horse and methods to study cytotoxic T-lymphocyte responses were developed. Also, two different marker vaccination strategies, a recombinant sub-unit vaccine and genetically modified live virus, were evaluated. These studies were complementary to contract research clinical trials to evaluate the efficacy of EAV vaccines.


Arbovirology research

I began to work on equine arbovirology during my last three years at the Animal Health Trust, specifically on West Nile virus (WNV) and African horse sickness (AHS). During this period I developed a horse challenge model and set up serological assays for West Nile virus infection. I also set up in vitro systems to study the factors that influence neuro-invasiveness and neuro-virulence of WNV in the horse. Also, together with colleagues at AHT and at IAH we collectively acquired funds from the BBSRC (Biotechnology and Biological Sciences Research Council) to work on a project aimed at developing novel vaccination approaches for (AHS) based on poxvirus vectors.


African horse sickness

In 2007 I joined the Vector-Borne Diseases Programme at The Pirbright Institute (formerly IAH), to work on vaccine development for Orbiviral diseases, specifically African horse sickness and bluetongue virus (BTV). The main focus of my research is the development of efficacious, safe vaccination strategies for AHS and BTV which can be applied in non-endemic countries.
We have generated a recombinant modified vaccinia virus (MVA-AHSV-VP2) vaccine that delivers (expresses) the relevant protective antigen of AHSV (VP2) upon inoculation of the host. We have so far completed MVA-VP2 vaccines for each of 7 AHSV types (out of the existing 9). The remaining two MVA-VP2 vaccines are currently being constructed.
Vaccination studies in a mouse model, developed by us, and in the target species, showed that MVA-VP2 does not cause significant adverse effects and protected against lethal AHSV infection. It was also possible to determine whether vaccinated horses have been infected with AHSV. Furthermore, we have demonstrated that a polyvalent AHS vaccination regime could be developed using combinations of single MVA-VP2 recombinants, each expressing a single VP2 from a different AHSV type. Our research has also shown that protection conferred by MVA-VP2 against AHSV is mediated mainly by antibodies and that passive immunization with MVA-VP2 specific antibodies is protective and could potentially be used as an emergency treatment for AHSV infection.

With support from DEFRA, Genomia fund, BBSRC and commercial sponsors we are continuing this line of research and the prospects of comercialising a fully protective recombinant vaccine for AHSV are hopeful. In addition, we have conducted parallel vaccine research on BTV.

 

Molecular diagnostics for AHSV

Development of improved diagnostic methods for AHSV is another focus of my current research activities and novel methods have been published recently. These novel diagnostic methods are currently being validated in an International ring trial led by Pirbright and the other OIE (World Organisation for Animal Health) reference laboratories. In 2013 I became designated OIE expert on African horse sickness.

Others:

- Member of the Royal College of Veterinary Surgeons since 1993
- Home Office Personal Licence Holder since 1994
- Home Office Project Licence Holder since 2006
- Lecturer on African horse sickness for the International course on Transboundary Diseases organized yearly by CISA, Valdeolmos, Madrid.
- Lecturer on African horse sickness and Equine viral arteritis for the MSc Veterinary Microbiology, Faculty of Veterinary Sceince, University of Surrey
- In 2013 I became OIE (World Organisation for Animal Health) designated expert in African horse sickness

Awards / Prizes

- September 2013: Pirbright Institute award for best science with commercial impact
- October 2012: Merit award by the Korean Society of Veterinary Science for the seminar: ‘African horse sickness – Are we prepared for an outbreak?’. Seoul, Korea 2012.
- October 2012: Merit award for the presentation: African horse sickness at International symposium of Veterinay Medicine, National University of Chungnam, South Korea.

Collaborations

Fruitful interaction with scientists, policy makers and veterinarians from other Academic Institutions, Research Institutes, government bodies (DEFRA, VMD), International organisations (OIE) and the Equine and vaccine industries (UK and abroad, in particular South Africa) were developed over the years. These interactions improved scientific, societal and commercial output and impact of our research. Relevant interactions include:

Dr Javier Ortego (CISA, Valdeolmos, Madrid, Spain)
Prof Sarah Gilbert (Jenner Institute, University of Oxford, UK)
Prof Linda King (Oxford Brookes University)
Prof Duncan Hannant (University of Nottingham, UK)
Dr Linda Lua (University of Queensland, Australia)
Dr Alison Lubisi (Onderstepoort Veterinary Institute, South Africa) - OIE
Dr Montserrat Aguero (LCV, Madrid, Spain) – OIE
Prof JM Sanchez-Vizcaino (University Complutensae de Madrid, Spain) - OIE
Prof Stephan Zientara (ANSES, Maisons-Alfort, Paris, France)
Dr Richard Newton (Animal Health Trust, Newmarket, UK),
Professor Tony Fooks (AHVLA, Addlestone, UK)
Dr Eileen Ostlund (USDA, Ames, Iowa)
Dr Theo Kanellos, Zoetis Animal Health
Dr Jeremy Salt, Zoetis Animal Health
Dr Alicia Urniza, Zoetis Animal Health

Publications:

Alberca, B., Bachanek-Bankowska, K., Cabana, M., Calvo-Pinilla, E., Viaplana, E., Frost, L., Gubbins, S., Urniza, A., Mertens, P. & Castillo-Olivares, J. (2014). Vaccination of horses with a recombinant modified vaccinia Ankara virus (MVA) expressing African horse sickness (AHS) virus major capsid protein VP2 provides complete clinical protection against challenge. Vaccine 32, 3670-3674.
Bachanek-Bankowska, K., Maan, S., Castillo-Olivares, J., Manning, N. M., Maan, N. S., Potgieter, A. C., Di Nardo, A., Sutton, G., Batten, C. & Mertens, P. P. (2014). Real time RT-PCR assays for detection and typing of African horse sickness virus. PloS one 9, e93758.
Calvo-Pinilla, E., Castillo-Olivares, J.*, Jabbar, T., Ortego, J., de la Poza, F. & Marin-Lopez, A. (2014). Recombinant vaccines against bluetongue virus. Virus research 182, 78-86.
Calvo-Pinilla, E., de la Poza, F., Gubbins, S., Mertens, P. P., Ortego, J. & Castillo-Olivares, J. (2014). Vaccination of mice with a modified Vaccinia Ankara (MVA) virus expressing the African horse sickness virus (AHSV) capsid protein VP2 induces virus neutralising antibodies that confer protection against AHSV upon passive immunisation. Virus research 180, 23-30.
Capocefalo, A., Franceschi, V., Mertens, P. P., Castillo-Olivares, J., Cavirani, S., Di Lonardo, E., Leni, Z. & Donofrio, G. (2010). Expression and secretion of Bluetongue virus serotype 8 (BTV-8)VP2 outer capsid protein by mammalian cells. Journal of virological methods 169, 420-424.
Castillo-Olivares, J., Calvo-Pinilla, E., Casanova, I., Bachanek-Bankowska, K., Chiam, R., Maan, S., Nieto, J. M., Ortego, J. & Mertens, P. P. (2011). A modified vaccinia Ankara virus (MVA) vaccine expressing African horse sickness virus (AHSV) VP2 protects against AHSV challenge in an IFNAR -/- mouse model. PloS one 6, e16503.
Castillo-Olivares, J., de Vries, A. A., Raamsman, M. J., Rottier, P. J., Lakhani, K., Westcott, D., Tearle, J. P., Wood, J. L., Mumford, J. A., Hannant, D. & Davis-Poynter, N. J. (2001). Evaluation of a prototype sub-unit vaccine against equine arteritis virus comprising the entire ectodomain of the virus large envelope glycoprotein (G(L)): induction of virus-neutralizing antibody and assessment of protection in ponies. The Journal of general virology 82, 2425-2435.
Castillo-Olivares, J., Mansfield, K. L., Phipps, L. P., Johnson, N., Tearle, J. & Fooks, A. R. (2011). Antibody response in horses following experimental infection with West Nile Virus lineages 1 and 2. Transboundary and emerging diseases 58, 206-212.
Castillo-Olivares, J., Tearle, J. P., Montesso, F., Westcott, D., Kydd, J. H., Davis-Poynter, N. J. & Hannant, D. (2003). Detection of equine arteritis virus (EAV)-specific cytotoxic CD8+ T lymphocyte precursors from EAV-infected ponies. The Journal of general virology 84, 2745-2753.
Castillo-Olivares, J., Wieringa, R., Bakonyi, T., de Vries, A. A., Davis-Poynter, N. J. & Rottier, P. J. (2003). Generation of a candidate live marker vaccine for equine arteritis virus by deletion of the major virus neutralization domain. Journal of virology 77, 8470-8480.
Castillo-Olivares, J. & Wood, J. (2004). West Nile virus infection of horses. Veterinary research 35, 467-483.
Chiam, R., Sharp, E., Maan, S., Rao, S., Mertens, P., Blacklaws, B., Davis-Poynter, N., Wood, J. & Castillo-Olivares, J. (2009). Induction of antibody responses to African horse sickness virus (AHSV) in ponies after vaccination with recombinant modified vaccinia Ankara (MVA). PloS one 4, e5997.
de la Poza, F., Calvo-Pinilla, E., Lopez-Gil, E., Marin-Lopez, A., Mateos, F., Castillo-Olivares, J., Lorenzo, G. & Ortego, J. (2013). Ns1 is a key protein in the vaccine composition to protect Ifnar(-/-) mice against infection with multiple serotypes of African horse sickness virus. PloS one 8, e70197.
Geraghty, R. J., Newton, J. R., Castillo-Olivares, J., Cardwell, J. M. & Mumford, J. A. (2003). Testing for equine arteritis virus. The Veterinary record 152, 755.
Geraghty, R. J., Newton, J. R., Castillo-Olivares, J., Cardwell, J. M. & Mumford, J. A. (2003). Testing for equine arteritis virus. The Veterinary record 152, 478-479.
Jabbar, T. K., Calvo-Pinilla, E., Mateos, F., Gubbins, S., Bin-Tarif, A., Bachanek-Bankowska, K., Alpar, O., Ortego, J., Takamatsu, H. H., Mertens, P. P. & Castillo-Olivares, J. (2013). Protection of IFNAR (-/-) mice against bluetongue virus serotype 8, by heterologous (DNA/rMVA) and homologous (rMVA/rMVA) vaccination, expressing outer-capsid protein VP2. PloS one 8, e60574.
Liu, L., Castillo-Olivares, J., Davis-Poynter, N. J., Baule, C., Xia, H. & Belak, S. (2008). Analysis of ORFs 2b, 3, 4, and partial ORF5 of sequential isolates of equine arteritis virus shows genetic variation following experimental infection of horses. Veterinary microbiology 129, 262-268.
Newton, J. R., Geraghty, R. J., Castillo-Olivares, J., Cardwell, J. M. & Mumford, J. A. (2004). Evidence that use of an inactivated equine herpesvirus vaccine induces serum cytotoxicity affecting the equine arteritis virus neutralisation test. Vaccine 22, 4117-4123.
Nugent, J., Sinclair, R., deVries, A. A., Eberhardt, R. Y., Castillo-Olivares, J., Davis Poynter, N., Rottier, P. J. & Mumford, J. A. (2000). Development and evaluation of ELISA procedures to detect antibodies against the major envelope protein (G(L)) of equine arteritis virus. Journal of virological methods 90, 167-183.
Edwards, S., Castillo-Olivares, J., Cullinane, A., Lable, J., Lenihan, J., Mumford, J. A., Paton, D. J., Pearson, J. E., Sinclair, R., Westcott, D. G. F., Wood, J. L. N., Zientara, S., and M. Nelly. 1998. International harmonization of laboratory diagnostic tests for equine viral arteritis. In Proceedings of the 8th International Conference on Equine Infectious Diseases, pp. 359-362. Edited by U. Wernery, J. F. Wade, J. A. Mumford & O. -R. Kaaden. Newmarket: R&W Publications.
J.L.N.Wood, J.Cardwell, J.Castillo-Olivares & V.Irwin (2007). Transmission of Diseases through Semen. In Current Therapy in Equine Reproduction, pp. 266-275. Edited by Juan Samper, Jonathan Pycock and Angus McKinnon. Saunders Elsevier

Grants

1.DEFRA – (2009 - 2015): The development of novel subunit vaccines and viral delivery mechanisms for African horse sickness virus antigens

2.Genomia seed fund (2013 – 2015): Development of recombinant vaccines for African horse sickness based on modified vaccinia Ankara

3.Pfizer funded studentship (2011 – 2015): The use of African horse sickness VP7 crystals as a vaccine delivery system

4.BBSRC CASE / Industrial PhD studentship award (2013 - 2017): Overcoming antigenic variability of African horse sickness virus (AHSV) using a vaccination strategy based on epitope deletion

5.Pirbright seed fund / Oxford Brookes University (2013 - 2017): Recombinant Vaccines for African Horse Sickness Based on Baculovirus Pseudotyping and Transduction

6.BBSRC (2004 - 2008): Epidemiology and control of orbiviral diseases in the UK, with particular reference to bluetongue and African horse sickness