Vaccination of ponies with the IE gene of EHV-1 in a recombinant modified live vaccinia vector protects against clinical and virological disease

Soboll, Gisela; Breathnach, Cormac C.; Kydd, Julia H.; Hussey, Stephen B.; Mealey, Robert H.; Lunn, D.P.

doi:10.1016/j.vetimm.2009.11.009

Cited by 25 publications

(35 citation statements)

References 31 publications

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“…It is important to also consider these results in the context of previous data that suggested that Eqca-1*00101 had a protective effect in terms of EHV-1 infection outcomes after vaccination, where the IE gene of EHV-1 was cloned into a NYVAC vaccine that stimulated IFN-γ+T lymphocytes in PBMCs from Eqca-1*00101 horses and reduced cell-associated viremia showing an efficacious induction of cellular immunity against an IE expression construct in vivo (Paillot et al 2006; Soboll et al 2010). That suggests, paradoxically, that a narrow repertoire might be beneficial with respect to control of, or protection against, EHV-1 infection, perhaps allowing a more focused response, or avoiding “immune diversion” or “decoy” responses, which have been described in the case of other herpesviruses (Gillet et al 2007).…”

Section: Discussionmentioning

confidence: 92%

The common equine class I molecule Eqca-1*00101 (ELA-A3.1) is characterized by narrow peptide binding and T cell epitope repertoires

et al. 2015

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Here we describe a detailed quantitative peptide-binding motif for the common equine leukocyte antigen (ELA) class I allele Eqca-1*00101, present in roughly 25 % of Thoroughbred horses. We determined a preliminary binding motif by sequencing endogenously bound ligands. Subsequently, a positional scanning combinatorial library (PSCL) was used to further characterize binding specificity and derive a quantitative motif involving aspartic acid in position 2 and hydrophobic residues at the C-terminus. Using this motif, we selected and tested 9- and 10-mer peptides derived from the equine herpesvirus type 1 (EHV-1) proteome for their capacity to bind Eqca-1*00101. PSCL predictions were very efficient, with an receiver operating characteristic (ROC) curve performance of 0.877, and 87 peptides derived from 40 different EHV-1 proteins were identified with affinities of 500 nM or higher. Quantitative analysis revealed that Eqca-1*00101 has a narrow peptide-binding repertoire, in comparison to those of most human, non-human primate, and mouse class I alleles. Peripheral blood mononuclear cells from six EHV-1-infected, or vaccinated but uninfected, Eqca-1*00101-positive horses were used in IFN-γ enzyme-linked immunospot (ELISPOT) assays. When we screened the 87 Eqca-1*00101-binding peptides for T cell reactivity, only one Eqca-1*00101 epitope, derived from the intermediate-early protein ICP4, was identified. Thus, despite its common occurrence in several horse breeds, Eqca-1*00101 is associated with a narrow binding repertoire and a similarly narrow T cell response to an important equine viral pathogen. Intriguingly, these features are shared with other human and macaque major histocompatibility complex (MHC) molecules with a similar specificity for D in position 2 or 3 in their main anchor motif.

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Section: Discussionmentioning

confidence: 92%

The common equine class I molecule Eqca-1*00101 (ELA-A3.1) is characterized by narrow peptide binding and T cell epitope repertoires

et al. 2015

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“…In Experiments 2 and 3, nasal swabs for detection of EHV-1 viral shedding were collected using a sterile, 6-inch DACRON swab (Fisher Scientific Inc. Pittsburgh, PA, USA) as previously described [20]. The swab was inserted into one nostril and then the tip was placed in 1 mL virus isolation transport media (MEM with Gentamicin and Amphotericin B).…”

Section: Methodsmentioning

confidence: 99%

“…Blood was collected by jugular venipuncture into heparinized tubes in all instances, and PBMC were separated as previously described [20]. In addition, in experiment 3, blood was collected into heparin on days 5 through 10 to determine GFP expression in PBMCs.…”

Section: Methodsmentioning

confidence: 99%

“…In addition, in experiment 3, blood was collected into heparin on days 5 through 10 to determine GFP expression in PBMCs. For this purpose, PBMCs were isolated as previously described [20] and GFP expression was evaluated using flow cytometry.…”

Section: Methodsmentioning

confidence: 99%

“…β-actin was used as the cellular housekeeping gene using primers and probe as developed previously [22]. Viral load was expressed as the log of EHV-1 gB DNA copies / 10 6 β-actin copies [20]. …”

Section: Methodsmentioning

confidence: 99%

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Experimental infection with equine herpesvirus type 1 (EHV-1) induces chorioretinal lesions

Hussey

Goehring

Lunn

et al. 2013

Vet Res

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Equine herpesvirus myeloencephalitis (EHM) remains one of the most devastating manifestations of equine herpesvirus type 1 (EHV-1) infection but our understanding of its pathogenesis remains rudimentary, partly because of a lack of adequate experimental models. EHV-1 infection of the ocular vasculature may offer an alternative model as EHV-1-induced chorioretinopathy appears to occur in a significant number of horses, and the pathogenesis of EHM and ocular EHV-1 may be similar. To investigate the potential of ocular EHV-1 as a model for EHM, and to determine the frequency of ocular EHV-1, our goal was to study: (1) Dissemination of virus following acute infection, (2) Development and frequency of ocular lesions following infection, and (3) Utility of a GFP-expressing virus for localization of the virus in vivo. Viral antigen could be detected following acute infection in ocular tissues and the central nervous system (experiment 1). Furthermore, EHV-1 infection resulted in multifocal choroidal lesions in 90% (experiment 2) and 50% (experiment 3) of experimentally infected horses, however ocular lesions did not appear in vivo until between 3 weeks and 3 months post-infection. Taken together, the timing of the appearance of lesions and their ophthalmoscopic features suggest that their pathogenesis may involve ischemic injury to the chorioretina following viremic delivery of virus to the eye, mirroring the vascular events that result in EHM. In summary, we show that the frequency of ocular EHV-1 is 50-90% following experimental infection making this model attractive for testing future vaccines or therapeutics in an immunologically relevant age group.

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Equine Herpesviruses

Gulati¹,

Virmani²,

Tripathi³

2019

Recent Advances in Animal Virology

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Vaccination of ponies with the IE gene of EHV-1 in a recombinant modified live vaccinia vector protects against clinical and virological disease

Cited by 25 publications

References 31 publications

The common equine class I molecule Eqca-1*00101 (ELA-A3.1) is characterized by narrow peptide binding and T cell epitope repertoires

The common equine class I molecule Eqca-1*00101 (ELA-A3.1) is characterized by narrow peptide binding and T cell epitope repertoires

Experimental infection with equine herpesvirus type 1 (EHV-1) induces chorioretinal lesions

Equine Herpesviruses

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