Generation of a candidate live marker vaccine for equine arteritis virus by deletion of the major virus neutralization domain.
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 G(L), 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-G(L)Delta, 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-G(L)Delta did not induce a measurable response in our G(L)-peptide ELISA while the challenge infection of the animals clearly did. EAV-G(L)Delta or similar mutants are therefore attractive marker vaccine candidates, enabling serological discrimination between vaccinated and wild-type virus-infected animals.
Publication Date: 2003-07-15 PubMed ID: 12857916PubMed Central: PMC165223DOI: 10.1128/jvi.77.15.8470-8480.2003Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The researchers have produced a live candidate marker vaccine for equine arteritis virus (EAV), by removing a crucial area of the virus that stimulates immune responses. However, the deletion doesn’t compromise the vaccine’s effectiveness, suggesting that another immune mechanism provides protection against infection. The modified virus could help differentiate between vaccinated and wild-type virus-infected animals.
Introduction to the Research
- The focus of the research lies in the development of a vaccine for the equine arteritis virus (EAV), a perpetrator of respiratory and reproductive diseases amongst horses. This virus belongs to the Arteriviridae family of viruses in the order of Nidovirales.
- Previously, a peptide enzyme-linked immunosorbent assay (ELISA) was developed, which effectively detected EAV presence owing to the virus-neutralizing antibodies targeting a dominant region of EAV – the G(L) domain.
Research Methodology
- The researchers utilized an infectious cDNA to create a mutant EAV that lacked the immunodominant G(L) domain. This manipulated virus expressed regular titers in cultured cells, but at a slower rate and caused no symptoms when introduced to ponies.
- The antibodies produced in response to this mutant virus effectively neutralized it in vitro but showed limited efficacy against wild-type strains of EAV.
- The researchers further exposed the vaccinated ponies to the more virulent strains of EAV and found these animals to be fully protected against disease, with only brief, low levels of viral replication noted. This protection level hints at the presence of an immune effector mechanism that provides protection against infection beyond the neutralization by antibodies.
Implications and Conclusion
- Interestingly, the infection with the mutant EAV (EAV-G(L)Delta) did not induce a measurable response in the G(L) peptide-based ELISA. However, the EAV infection did show a clear reaction in the same ELISA, enabling researchers to distinguish between vaccinated and wild-type virus-infected animals.
- Therefore, the researchers propose mutant viruses like EAV-G(L)Delta as promising marker vaccine candidates that facilitate distinguishing between vaccinated and infected animals – an essential feature for disease control and eradication strategies.
Cite This Article
APA
Castillo-Olivares J, Wieringa R, Bakonyi T, de Vries AA, Davis-Poynter NJ, Rottier PJ.
(2003).
Generation of a candidate live marker vaccine for equine arteritis virus by deletion of the major virus neutralization domain.
J Virol, 77(15), 8470-8480.
https://doi.org/10.1128/jvi.77.15.8470-8480.2003 Publication
Researcher Affiliations
- Centre for Preventive Medicine, Animal Health Trust, Kentford, Newmarket, Suffolk CB8 7UU, United Kingdom.
MeSH Terms
- Animals
- Antibodies, Viral / blood
- Antibodies, Viral / immunology
- Arterivirus Infections / immunology
- Arterivirus Infections / prevention & control
- Arterivirus Infections / veterinary
- Arterivirus Infections / virology
- Cell Line
- Cells, Cultured
- Cricetinae
- Equartevirus / genetics
- Equartevirus / immunology
- Equartevirus / metabolism
- Equartevirus / pathogenicity
- Horse Diseases / immunology
- Horse Diseases / prevention & control
- Horse Diseases / virology
- Horses
- Immunization
- Lung / cytology
- Neutralization Tests
- Sequence Deletion
- Vaccines, Marker
- Viral Envelope Proteins / genetics
- Viral Vaccines / administration & dosage
- Viral Vaccines / genetics
- Viral Vaccines / immunology
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