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Title: Antibodies to ovine herpesvirus 2 glycoprotein antibodies decrease virus infectivity and prevent malignant catarrhal fever in rabbits

item CUNHA, CRISTINA - Washington State University
item Knowles Jr, Donald
item Taus, Naomi
item O'TOOLE, D - University Of Wyoming
item NICOLA, A - Washington State University
item AGUILAR, H - Washington State University
item Li, Hong

Submitted to: Veterinary Microbiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/17/2014
Publication Date: 12/9/2014
Citation: Cunha, C.W., Knowles Jr, D.P., Taus, N.S., O'Toole, D., Nicola, A.V., Aguilar, H.C., Li, H. 2014. Antibodies to ovine herpesvirus 2 glycoprotein antibodies decrease virus infectivity and prevent malignant catarrhal fever in rabbits. Veterinary Microbiology. 175(2-4):349-355.

Interpretive Summary: Ovine herpesvirus 2 (OvHV-2) is a herpesvirus carried asymptomatically by sheep, its well-adapted natural host, but causes sheep-associated malignant catarrhal fever (SA-MCF) when transmitted to non-adapted hosts, such as bison, cattle and deer. SA-MCF is one of the most important infectious diseases for the bison industry in North America and development of an effective vaccine to protect bison from the disease has become the priority to the industry. In this study we used rabbits as a model to measure ability of the antibodies to block OvHV-2 entry. Specific antibodies against OvHV-2 glycoproteins B, H and L were generated in rabbits after immunization of plasmid DNA expressing the respective viral genes using a gene gun delivery. The rabbit antisera were incubated with a defined amount of virus prior to intranasal aerosolization of rabbits. The results showed that blocking of OvHV-2 infection in rabbits was significantly greater when the virus was treated with antibodies against one or more viral glycoproteins than when treated with control sera without OvHV-2-specific antibodies. The data indicate that antibodies against OvHV-2 glycoproteins B, H and L block virus entry in rabbits and thus are suitable candidates to be tested in a vaccine aiming at stimulating neutralizing antibody responses.

Technical Abstract: Ovine herpesvirus-2 (OvHV-2) is the etiological agent of sheep-associated malignant catarrhal fever (SA-MCF), a generally fatal lymphoproliferative disease of many species in the order Artiodactyla. Development of a vaccine is critical to prevent mortality. Because OvHV-2 has not been cultured in vitro, SA-MCF research is hindered by the lack of in vitro tools to study viral constituents and specific host immune responses. As an alternative, in this study the neutralizing activity of antibodies against OvHV-2 glycoproteins gB and gH/gL was evaluated in vivo using rabbits as a model. OvHV-2-specific antibodies were developed in rabbits by immunization using biolistic delivery of plasmids expressing the desired genes. A lethal dose of OvHV-2 was incubated with the antisera and then nebulized into rabbits. Virus neutralization was assessed by measuring several infection parameters associated with virus infectivity. Anti-gB or anti-gH/gL antibodies alone blocked infection in five out of six (83%) rabbits, while a combination of anti-gB and anti-gH/gL antibodies protected six out of six (100%) rabbits from infection. These results indicate that OvHV-2 gB and gH/gL antibodies are capable of neutralizing the virus and preventing SA-MCF in rabbits, thus OvHV-2 gB and gH/gL are suitable targets for SA-MCF vaccine development aimed at stimulating neutralizing antibody responses.