Location: Animal Disease ResearchTitle: Replacement of glycoprotein B in alcelaphine herpesvirus 1 by its ovine herpesvirus 2 homolog: Implications in vaccine development for sheep-associated malignant catarrhal fever
|Dewals, Benjamin - UNIVERSITY OF LIEGE|
|Vanderplasschen, Alain - UNIVERSITY OF LIEGE|
|Knowles Jr, Donald|
Submitted to: mSphere
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/14/2016
Publication Date: 8/3/2016
Citation: Cunha, C.W., Taus, N.S., Dewals, B.G., Vanderplasschen, A., Knowles, D.P., Li, H. 2016. Replacement of glycoprotein B in alcelaphine herpesvirus 1 by its ovine herpesvirus 2 homolog: Implications in vaccine development for sheep-associated malignant catarrhal fever. mSphere. doi:10.1128/mSphere.00108-16.
Interpretive Summary: Ovine herpesvirus 2 (OvHV-2) is the herpesvirus causing sheep-associated malignant catarrhal fever (SA-MCF), an often fatal disease of ruminants. In North America, SA-MCF poses a serious threat for bison due to their high disease susceptibility and the development of a vaccine is a top priority for research. One of the major challenges to develop a vaccine for SA-MCF is that OvHV-2 cannot grow in cell culture and, consequently, it is not possible to modify the virus to be used as a vaccine without causing disease. As an alternative, in this study we used a close relative of OvHV-2, alcelaphine herpesvirus 1 (AlHV-1) that can grow in cell culture and has been modified to do not cause disease, as a vaccine vehicle to carry an OvHV-2 protein. A chimeric virus containing the OvHV-2 glycoprotein B (gB) gene was constructed and characterized. OvHV-2 gB was chosen because it can induce antibody responses capable of blocking virus infection. We demonstrated that the chimeric virus grows in cell culture, produces the OvHV-2 gB protein, and that its infectivity can be blocked by anti-OvHV-2-gB antibodies. In vivo studies using a rabbit model showed that the chimeric virus does not cause disease and is capable to induce antibodies against OvHV-2 gB. Together, these results indicate that the AlHV-1/OvHV-2 chimeric virus is an attractive alternative to develop a vaccine for SA-MCF and a potential tool for detection of OvHV-2 gB neutralizing antibodies.
Technical Abstract: Vaccine development is a top priority in malignant catarrhal fever (MCF) research. In the case of sheep-associated MCF (SA-MCF), caused by ovine herpesvirus 2 (OvHV-2), progress towards this objective has been hindered by the absence of methods to attenuate or modify the virus, since it cannot be propagated in vitro. As an alternative, in this study we used a non-pathogenic alcelaphine herpesvirus 1 (AlHV-1), which has been cloned as a bacterial artificial chromosome, as a backbone to express OvHV-2 glycoprotein B (gB), one of the candidates for a SA-MCF vaccine. Using homologous recombination and the galK selection system, the AlHV-1 gB gene was successfully replaced by the OvHV-2 gB gene, generating a AlHV-1/OvHV-2 chimeric virus identified as AlHV-1'ORF73 /OvHV-2-ORF8. The chimeric virus was able to infect and replicate in cell culture. AlHV-1'ORF73 /OvHV-2-ORF8 was nonpathogenic for rabbits and induced production of antibodies against the OvHV-2 gB protein. Furthermore, we demonstrated that the chimeric virus can be used in a neutralization assay to measure neutralizing antibodies to OvHV-2 gB. The development of an AlHV-1/OvHV-2 chimeric virus is a significant step towards an SA-MCF vaccine and provides a valuable tool for OvHV-2 biology studies.