Rotavirus is the most common cause of clinical diarrhea with gastrointestinal symptoms in foals less than 6-months-old. It is transmitted through the oral-fecal route. When foals get infected with an equine rotavirus, they can develop severely watery to bloody diarrhea. It can become life threatening for infected foals if left untreated. Currently, there are two groups of rotaviruses circulating in horses. Equine rotavirus Group A, (consisting of two distinct G3P and G14P genotypes), is the most common, followed by equine rotavirus Group B. Both rotavirus groups are highly contagious and produce similar symptoms in infected foals, including inappetence, lethargy, dehydration, severe electrolyte imbalance and watery yellow diarrhea.  

Equine rotaviruses A and B are similar in viral genome structure and morphology. The genome in both viruses consists of 11 sets of genes, and these gene sets are enclosed within the capsid proteins. Morphologically, both viruses show a wheel-like shape with icosahedral symmetry without an envelope, which is built by the triple-layered capsid proteins with a diameter of 80–100 nm in size. The inner layer is made up with the VP2 protein, while the middle layer is composed of the VP6 protein. The VP7 protein forms the outer layer protein from which viral spike protein VP4 protrudes. Of the three concentric layers, VP4 and VP7 proteins in the outer capsid shell are responsible for the virus entering the epithelial cells in the villi of the small intestine and spreading infection, causing diarrhea in foals. The VP4 protein is cleaved by cellular proteases into two subunits, VP8* and VP5*, with VP8* involved in binding the cell surface glycan receptor and VP5* responsible for the host cell membrane penetration. VP7 function remains poorly understood but its roles in viral uncoating, genome transcription and viral assembly have been proposed.  

Because VP4 (VP8*and VP5*) and VP7 proteins are on the surface of rotaviruses, they are the first group of viral proteins that gets recognized by the equine immune system when a foal is exposed to a rotavirus. The direct communication between the immune system and viral surface proteins (VP4 and VP7) activates B lymphocytes, which triggers the production of specific antibodies against VP4 and VP7 proteins on that invading rotavirus. VP4 and VP7 proteins are called rotaviral antigens. Historically, according to the protein abundance and the magnitude of antibody production, VP4 is named as the minor antigen, while VP7 is dubbed as the major antigen. VP4- or VP7-specific antibodies bind to the VP4 or VP7 protein of infectious rotavirus particles and prevent them from attaching to and entering the intestinal epithelial cells of foals, which as a result, block rotavirus replication and disarm its infectivity and spread among foals. Such functional antibodies are scientifically viewed as virus-neutralizing antibodies that are immune correlates of protection.  

Despite equine rotaviruses A and B having a lot in common, including clinical symptoms and viral genome structure and morphology, there are substantial differences between the two rotavirus groups in horses. One notable difference is that equine rotaviruses A and B have different VP4 and VP7 proteins that are on the outer layer of their virus particles. In this context, antibodies raised against VP4 or VP7 protein of an equine rotavirus A will not recognize and bind its counterpart on the surface of an equine rotavirus B, and the reverse is also true. And therefore, the Zoetis Rotavirus Group A vaccine, extensively used in equine industry for control and prevention of circulating rotavirus A infection in horses, will not protect foals against infection by equine rotavirus B. Lacking cross-protection between equine rotavirus A and B has been clearly demonstrated during the recent equine rotavirus B outbreaks: foals born to dams receiving Zoetis Rotavirus Group A vaccine came down with clinical diarrhea caused by rotavirus B, not rotavirus A.  

In response to a critical need to develop an equine rotavirus B vaccine, through partnership and collaboration with the biotech company and equine industry, the Gluck Equine Research Center has developed two forms of equine rotavirus B vaccines with different mechanisms of action. One vaccine is designed to stimulate the production of antibodies to block the attachment of equine rotavirus B particles to the equine intestinal epithelial cells, the in vivo target cells of equine rotavirus B. The second vaccine is designed to generate antibodies to disrupt the entry process of equine rotavirus B and disarm its infectivity and spread. The proofof-concept has been demonstrated in recently completed trials involving adult horses and mares/foals. The Gluck Center’s equine researchers showed that both vaccines are safe, immunogenic and effective to protect foals from equine rotavirus B infection. Currently, the Gluck Equine Research Center is collaborating with its industry partner to further develop the equine rotavirus B vaccine towards its commercialization so it can be used for control and prevention of foal diarrhea caused by equine rotavirus B, a newly emerging disease in U.S. horses. 

This is an excerpt from Equine Disease Quarterly, Vol. 35, Issue 1, funded by underwriters at Lloyd’s, London, brokers, and their Kentucky agents. It was written by Feng Li, PhD, DVM, professor and William Robert Mills Endowed Chair at the University of Kentucky’s Gluck Equine Research Center, in Lexington.