Orf Virus-Based Vaccine Vector D1701-V Induces Strong CD8+ T Cell Response against the Transgene but Not against ORFV-Derived Epitopes.

Alena Reguzova,Michael Ghosh,Ralf Amann,Hanns-Joachim Rziha,Melanie Müller

doi:10.3390/vaccines8020295

Abstract

The potency of viral vector-based vaccines depends on their ability to induce strong transgene-specific immune response without triggering anti-vector immunity. Previously, Orf virus (ORFV, Parapoxvirus) strain D1701-V was reported as a novel vector mediating protection against viral infections. The short-lived ORFV-specific immune response and the absence of virus neutralizing antibodies enables repeated immunizations and enhancement of humoral immune responses against the inserted antigens. However, only limited information exists about the D1701-V induced cellular immunity. In this study we employed major histocompatibility complex (MHC) ligandomics and immunogenicity analysis to identify ORFV-specific epitopes. Using liquid chromatography-tandem mass spectrometry we detected 36 ORFV-derived MHC I peptides, originating from various proteins. Stimulated splenocytes from ORFV-immunized mice did not exhibit specific CD8+ T cell responses against the tested peptides. In contrast, immunization with ovalbumin-expressing ORFV recombinant elicited strong SIINFEKL-specific CD8+ T lymphocyte response. In conclusion, our data indicate that cellular immunity to the ORFV vector is negligible, while strong CD8+ T cell response is induced against the inserted transgene. These results further emphasize the ORFV strain D1701-V as an attractive vector for vaccine development. Moreover, the presented experiments describe prerequisites for the selection of T cell epitopes exploitable for generation of ORFV-based vaccines by reverse genetics.

Highlights

Induction of strong transgene-specific immune responses and negligible anti-vector immunity are the prerequisites of efficient viral vector-based vaccines [1,2,3]
In this study we investigated the induction of transgene- and vector-specific CD8+ T lymphocyte responses by the ORFV strain D1701-V in mice
For the first time we report the identification of 36 unique D1701-V ORFV-derived

Summary

Introduction

Induction of strong transgene-specific immune responses and negligible anti-vector immunity are the prerequisites of efficient viral vector-based vaccines [1,2,3]. Orf virus (ORFV, Parapoxvirus) was reported as a novel viral vector for the expression of various foreign antigens. ORFV a promising viral vector candidate [4,5,6,7,8,9]. Different derivatives of the Vero cell culture adapted vector virus strain D1701-V were apathogenic even after high dose infection of immunosuppressed sheep [10]. The apathogenic Vero cell culture-adapted ORFV strain D1701-V has been used to generate recombinants by substituting viral genes with the foreign genes, which led to further attenuation [5,10,12]

Methods

Results

Conclusion