Equine herpesvirus type 1 modified live virus vaccines:<i>quo vaditis</i>?

Rosas, Cristina; Goodman, Laura B.; Einem, Jens von; Osterrieder, Nikolaus

doi:10.1586/14760584.5.1.119

Cited by 27 publications

(24 citation statements)

References 78 publications

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“…As a result of the conservative design of the dog experiment, which did not include a vector-only control, we cannot formally exclude that innate and unspecific responses not directed to H3 contribute to the protection conferred by the EHV-1 recombinant virus. Based on the notion that herpesviruses in general and EHV-1 in particular will dampen and subvert rather than induce innate responses, and based on experiments using RacH-derived modified live virus vaccines in horses, bovines and mice, we view the induction of an unspecific protective response as highly unlikely [11][12][13][14]. In addition and as discussed earlier, the rH_EIV vector induced a robust H3-specific antibody response as measured by ELISA and HI.…”

Section: Discussionmentioning

confidence: 87%

“…RacH-based vaccine vectors stably and efficiently deliver immunogenic proteins, induce both humoral and cellular immune responses, and they may also protect vaccinated animals from heterologous challenge [11][12][13]. EHV-1 RacH has a broad host range in cultured cells and infects both dividing and non-dividing cells from different hosts including canine cells [14].…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of a vectored equine herpesvirus type 1 (EHV-1) vaccine expressing H3 haemagglutinin in the protection of dogs against canine influenza

Rosas

Walle

Metzger

et al. 2008

Vaccine

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In 2004, canine influenza virus (CIV) was identified as a respiratory pathogen of dogs for the first time and is closely related to H3N8 equine influenza virus (EIV). We generated a recombinant vectored vaccine that expresses H3 of a recent isolate of EIV using equine herpesvirus type 1 (EHV-1) as the delivery vehicle. This EHV-1 vectored vaccine exhibited robust and stable EIV H3 expression and induced a strong influenza virus-specific response in both mice and dogs upon intranasal or subcutaneous administration. Furthermore, upon challenge with the recent CIV isolate A/canine/PA/ 10915-07, protection of vaccinated dogs could be demonstrated by a significant reduction in clinical sings, and, more importantly, by a significant reduction in virus shedding. We concluded that the EHV-1/H3 recombinant vector can be a valuable alternative for protection of dogs against clinical disease induced by CIV and can significantly reduce spread.

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Section: Discussionmentioning

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Evaluation of a vectored equine herpesvirus type 1 (EHV-1) vaccine expressing H3 haemagglutinin in the protection of dogs against canine influenza

Rosas

Walle

Metzger

et al. 2008

Vaccine

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“…Viruses including equine herpesvirus type 1 and 4 (EHV-1 and EHV-4), equine arteritis virus (EAV), and equine influenza virus (EIV) have plagued horses worldwide (Ostlund 1993). Particularly in the case of EHV-1 and EHV-4, vaccines are only partially effective (Patel and Heldens 2005; Rosas et al 2006). EHV-1, an α-herpesvirus, which primarily infects horses and wild equids, is the causative agent of rhinopneumonitis, abortions, and myeloencephalopathy (Ma et al 2013; Van de Walle et al 2009).…”

Section: Introductionmentioning

confidence: 99%

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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“…Another attenuated EHV-1 candidate vaccine strain is defective in gE alone [3]. These vaccine strains are highly attenuated in horses but only partially protect from respiratory symptoms after challenge [2,3,17,18].…”

Section: Pseudorabies Virus and Equine Herpes Virusmentioning

confidence: 99%

“…Attenuated live virus vaccines are safe and effective for several members of the alphaherpesvirus family, including varicella zoster virus (VZV), pseudorabies virus (PRV), and equine herpes virus 1 (EHV-1) [1][2][3][4]. Nevertheless, no effective vaccine is available to protect humans against herpes simplex virus 1 (HSV-1) or 2 (HSV-2) infection.…”

Section: Introductionmentioning

confidence: 99%

An Attenuated HSV-1 Live Virus Vaccine Candidate that is Replication Competent but Defective in Epithelial Cell-to-Cell and Neuronal Spread

Zumbrun

Friedman

2010

Replicating Vaccines

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Live attenuated vaccines represent the most successful approach for the prevention of alphaherpesvirus infections, including varicella zoster virus, pseudorabies virus, and equine herpes virus 1. It is reasonable to consider that live virus vaccines may also be effective for the prevention of other alphaherpesviruses, such as herpes simplex virus 1 (HSV-1) and 2 (HSV-2). An HSV-1 mutant strain that is deleted in glycoprotein E (gE), NS-gEnull, is replication competent but is defective in spread from one epithelial cell to another, from epithelial cells to axons, and from the neuron cell body into axons. The defect in spread likely accounts for the favorable safety profile of the live virus vaccine candidate in mice. The NS-gEnull mutant is also defective in immunoglobulin G (IgG) Fc receptor binding, which is a process used by the virus to escape antibody attack. NS-gEnull when used as an immunogen is highly effective in providing protection against epidermal and vaginal challenge by wild-type (WT) HSV-1 and HSV-2. NS-gEnull represents a novel HSV-1 vaccine approach that retains replication competency while impairing virus spread at the inoculation site and in neurons. Only gE is deleted from the vaccine strain, ensuring that most viral antigens are presented to the host. This strategy is worth considering for prevention of HSV-1 and possibly HSV-2.

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Equine herpesvirus type 1 modified live virus vaccines:quo vaditis?

Cited by 27 publications

References 78 publications

Evaluation of a vectored equine herpesvirus type 1 (EHV-1) vaccine expressing H3 haemagglutinin in the protection of dogs against canine influenza

Evaluation of a vectored equine herpesvirus type 1 (EHV-1) vaccine expressing H3 haemagglutinin in the protection of dogs against canine influenza

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

An Attenuated HSV-1 Live Virus Vaccine Candidate that is Replication Competent but Defective in Epithelial Cell-to-Cell and Neuronal Spread

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