Veterinary Microbiology and Pathology

Robert H. Mealey

Robert H. Mealey, DVM, PhD
Diplomate, American College of Veterinary Internal Medicine
Associate Professor of Immunology and Infectious Diseases
Equine Infectious Diseases Research Program (EQUID)
rhm@vetmed.wsu.edu
509-335-6672

Education and Training

Colorado State University, Fort Collins, CO	BS	1987	Veterinary Science
Colorado State University, Fort Collins, CO	DVM	1990	Veterinary Medicine
University of Minnesota, Saint Paul, MN	Internship	1991	Large Animal Medicine
Texas A&M University, College Station, TX	Residency	1995	Equine Medicine
Washington State University, Pullman, WA	PhD	2001	Immunology

Research Interests

Dr. Mealey is an equine internal medicine specialist and Associate Professor of immunology and infectious diseases in the Department of Veterinary Microbiology and Pathology in the College of Veterinary Medicine. He has devoted extensive research efforts to understand how the horse’s immune system controls persistent and vector-borne infections, including those caused by viruses, bacteria, and protozoan parasites. With support from the National Institutes of Health, USDA, Morris Animal Foundation, Grayson Jockey Club Research Foundation, and private donations, Dr. Mealey and his research team have focused primarily on equine infectious anemia virus, the cause of equine infectious anemia, and more recently, Theileria equi, a protozoan parasite that is a cause of equine piroplasmosis.

Equine infectious anemia virus (EIAV) has a world-wide distribution, and horses that become infected with EIAV are infected for life. Most infected horses have recurrent episodes of clinical disease, but eventually control the infection to become lifelong inapparent carriers of the virus. Collaborative work has shown that virus-specific immune responses are responsible for controlling EIAV replication. Cytotoxic T lymphocytes (CTL), which kill virus-infected cells, are a critical component of this virus-specific immune response, as are neutralizing antibodies. Our studies have focused on defining the correlates of CTL and neutralizing antibody-mediated protection against EIAV infection. Some of the objectives of ongoing work are to identify the viral proteins that must be recognized by protective CTL, as well as to determine the functional characteristics of protective CTL. Information gained thus far is being used to construct DNA and viral vector vaccines designed to induce EIAV-specific CTL in outbred horses. Ongoing studies also include determining the breadth and specificity of protective neutralizing antibody responses. Since EIAV is a lentivirus, similar to the human immunodeficiency virus, the results of these studies may also have implications for protecting people against AIDS.

Theileria equi (Babesia equi) is an apicomplexan protozoan parasite  that is a cause of the disease equine piroplasmosis. T. equi is transmitted by ticks, and once in the horse, the parasite infects red blood cells resulting in their destruction. Infected horses develop fever, lethargy, anorexia, anemia, and in severe cases, death. Importantly, surviving horses are infected for life, and these persistently infected horses become reservoir sources of infection for other horses. The disease occurs worldwide and is endemic in tropical, subtropical, and some temperate regions. It is estimated that only 10% of the world's horses reside in regions free of the disease, which is reportable to the World Organization for Animal Health. The disease is currently not considered endemic in the U.S., and the goal for U.S. regulatory agencies is to avoid becoming an endemic region. As a result, movement of T. equi positive horses is restricted in the U.S. Horses testing positive are denied entrance into the U.S., and domestic horses that test positive must be quarantined for life, euthanized, or if applicable, exported back to the country of origin. The majority of our recent collaborative work has been devoted to the critical evaluation of strategies for treatment, clearance, and determination of transmission risk for horses involved in the current outbreak of equine piroplasmosis in the United States. Our work to identify a consistently effective therapeutic drug regimen for clearance of this parasite, along with planned work to identify mechanisms to overcome drug resistance, represent lines of research that will improve the welfare of horses in the U.S. and throughout the world. Currently funded research is also focused on dissecting antibody and cell-mediated immune responses in horses that have been cleared of T. equi infection and to determine if these responses can prevent re-infection and/or clinical disease. This information will be critical for the development of protective vaccines which could play an important role in future T. equi control strategies in the U.S. and worldwide.

Professional Memberships

American Veterinary Medical Association
American College of Veterinary Internal Medicine
American Association of Equine Practitioners
American Association for Microbiology
Conference of Research Workers in Animal Disease

 

Selected Publications

1. Mealey RH, Fraser DG, Oaks JL, Cantor GH, McGuire TC. Immune reconstitution prevents continuous equine infectious anemia virus replication in an Arabian foal with severe combined immunodeficiency: lessons for control of lentiviruses. Clinical Immunology 101:237-247, 2001.   
2. Mealey RH, Zhang B, Leib SR, McGuire TC.  Epitope specificity is critical for high and moderate avidity cytotoxic T lymphocytes associated with control of viral load and clinical disease in horses with equine infectious anemia virus. Virology 313:537-552, 2003.
3. Fraser DG, Mealey RH, McGuire TC. Selecting peptides to optimize Th1 responses to an equine lentivirus using HLA-DR binding motifs and defined HIV-1 Th peptides. Immunogenetics 55:508-514, 2003.
4. McGuire TC, Leib SR, Mealey RH, Fraser DG, Prieur DJ.  Presentation and binding affinity of equine infectious anemia virus CTL envelope and matrix protein epitopes by an expressed equine classical MHC class I molecule. Journal of Immunology 171:1984-1993, 2003.
5. Mealey RH, Leib SR, Pownder SL, McGuire TC. Adaptive immunity is the primary force driving selection of equine infectious anemia virus envelope SU variants during acute infection. Journal of Virology 78:9295-9305, 2004.
6. Chung C, Mealey RH, McGuire TC. CTL from EIAV carrier horses with diverse MHC class I alleles recognize epitope clusters in Gag matrix and capsid proteins. Virology 327:144-154, 2004.
7. Patton KM, McGuire TC, Hines MT, Mealey RH, Hines SA. Rhodococcus equi-specific cytotoxic T lymphocytes in immune horses and development in asymptomatic foals. Infection and Immunity 73:2083-2093, 2005.
8. Mealey RH, Sharif A, Ellis SA, Littke MH, Leib SR, McGuire TC. Early detection of dominant Env-specific and subdominant Gag-specific CD8+ lymphocytes in equine infectious anemia virus-infected horses using major histocompatibility complex class I/peptide tetrameric complexes. Virology 339:110-126, 2005.
9. Chung C, Mealey RH, McGuire TC. Evaluation of high functional avidity CTL to Gag epitope clusters in EIAV carrier horses. Virology 342:228-239, 2005.
10. Mealey RH, Lee JH, Leib SR, Littke MH, McGuire TC. A single amino acid difference within the a-2 domain of two naturally occurring equine MHC class I molecules alters the recognition of Gag and Rev epitopes by equine infectious anemia virus-specific CTL. Journal of Immunology 177:7377-7390, 2006.
11. Mealey RH, Littke MH, Leib SR, Davis WC, McGuire TC. Cloning and large-scale expansion of epitope-specific equine cytotoxic T lymphocytes using an anti-equine CD3 monoclonal antibody and human recombinant IL-2. Veterinary Immunology and Immunopathology 118:121-128, 2007.
12. Mealey RH, Stone DM, Hines MT, Alperin DC, Littke MH, Leib SR, Leach SE, Hines SA. Experimental Rhodococcus equi and equine infectious anemia virus DNA vaccination in adult and neonatal horses: effect of IL-12, dose, and route. Vaccine 2007; 25:7582-97.
13. Mealey RH, Leib SR, Littke MH, Wagner B, Horohov DW, McGuire TC. Viral load and clinical disease enhancement associated with a lentivirus cytotoxic T lymphocyte vaccine regimen. Vaccine 2009; 27:2453-2468.
14. Taylor SD, Leib SR, Carpenter S, Mealey RH. Selection of a rare neutralization-resistant variant following passive transfer of convalescent immune plasma in equine infectious anemia virus-challenged SCID horses. Journal of Virology 2010; 84:6536-6548.
15. Ramsay JD, Leib SR, Orfe L, Call DR, Tallmadge RL, Fraser DG, Mealey RH. Development of a DNA microarray for detection of expressed equine classical MHC class I sequences in a defined population. Immunogenetics 2010; 62:633-639.
16. Harris SP, Fujiwara N, Mealey RH, Alperin, DC, Naka T, Goda R, Hines SA. Identification of Rhodococcus equi lipids recognized by host cytotoxic T lymphocytes. Microbiology 2010; 156:1836-1847.
17. Harris SP, Hines MT, Mealey RH, Alperin DC, Hines SA. Early development of cytotoxic T lymphocytes in neonatal foals following oral inoculation with Rhodococcus equi. Veterinary Immunology and Immunopathology 2011; 141:312-316.
18. Taylor SD, Leib SR, Wu W, Nelson R, Carpenter S, Mealey RH. Protective effects of broadly neutralizing immunoglobulin against homologous and heterologous equine infectious anemia virus infection in horses with severe combined immunodeficiency Journal of Virology 2011; 85:6814-6818.
19. Wu W, Blythe DC, Loyd H, Mealey RH, Tallmadge RL, Dorman KS, Carpenter S. Decreased infectivity of a neutralization‐resistant equine infectious anemia virus variant can be overcome by efficient cell‐to‐cell spread. Journal of Virology 2011; in press.
20. Mealey RH, Ueti MW, Kappmeyer LS, Wagner B, Knowles DP. Protective effects of passively transferred merozoite-specific antibodies against Theileria equi in horses with severe combined immunodeficiency. Clinical and Vaccine Immunology 2011; in press.

All Publications

Useful Links

Dr. Mealey is a founding faculty member of the Washington State University College of Veterinary Medicine’s Equine Infectious Diseases Research Program (EQUID).