Generation of a candidate live marker vaccine for equine arteritis virus by deletion of the major virus neutralization domain

Javier Castillo-Olivares, Roeland Wieringa, T. Bakonyi, Antoine A F De Vries, Nick J. Davis-Poynter, Peter J M Rottier

Research output: Contribution to journalArticle

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Abstract

Equine arteritis virus (EAV) is an enveloped plus-strand RNA virus of the family Arteriviridae (order Nidovirales) that causes respiratory and reproductive disease in equids. Protective, virus-neutralizing antibodies (VNAb) elicited by infection are directed predominantly against an immunodominant region in the membrane-proximal domain of the viral envelope glycoprotein GL, allowing recently the establishment of a sensitive peptide enzyme-linked immunosorbent assay (ELISA) based on this particular domain (J. Nugent et al., J. Virol. Methods 90:167-183, 2000). By using an infectious cDNA we have now generated, in the controlled background of a nonvirulent virus, a mutant EAV from which this immunodominant domain was deleted. This virus, EAV-GLΔ, replicated to normal titers in culture cells, although at a slower rate than wild-type EAV, and caused an asymptomatic infection in ponies. The antibodies induced neutralized the mutant virus efficiently in vitro but reacted poorly to wild-type EAV strains. Nevertheless, when inoculated subsequently with virulent EAV, the immunized animals, in contrast to nonvaccinated controls, were fully protected against disease; replication of the challenge virus occurred briefly at low though detectable levels. The levels of protection achieved suggest that an immune effector mechanism other than VNAb plays an important role in protection against infection. As expected, infection with EAV-GLΔ did not induce a measurable response in our GL-peptide ELISA while the challenge infection of the animals clearly did. EAV-GLΔ or similar mutants are therefore attractive marker vaccine candidates, enabling serological discrimination between vaccinated and wild-type virus-infected animals.

Original languageEnglish
Pages (from-to)8470-8480
Number of pages11
JournalJournal of Virology
Volume77
Issue number15
DOIs
Publication statusPublished - Aug 2003

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Marker Vaccines
Equine Arteritis Virus
Equine arteritis virus
neutralization tests
vaccines
Viruses
viruses
Immunodominant Epitopes
infection
Infection
Neutralizing Antibodies
neutralizing antibodies
mutants
Arteriviridae
Nidovirales
Enzyme-Linked Immunosorbent Assay
enzyme-linked immunosorbent assay
peptides
Peptides
reproductive disorders

ASJC Scopus subject areas

  • Immunology

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Generation of a candidate live marker vaccine for equine arteritis virus by deletion of the major virus neutralization domain. / Castillo-Olivares, Javier; Wieringa, Roeland; Bakonyi, T.; De Vries, Antoine A F; Davis-Poynter, Nick J.; Rottier, Peter J M.

In: Journal of Virology, Vol. 77, No. 15, 08.2003, p. 8470-8480.

Research output: Contribution to journalArticle

Castillo-Olivares, Javier ; Wieringa, Roeland ; Bakonyi, T. ; De Vries, Antoine A F ; Davis-Poynter, Nick J. ; Rottier, Peter J M. / Generation of a candidate live marker vaccine for equine arteritis virus by deletion of the major virus neutralization domain. In: Journal of Virology. 2003 ; Vol. 77, No. 15. pp. 8470-8480.
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