HSV-1 Amplicon Vectors as Genetic Vaccines

Abstract

HSV-1 amplicon vectors have been used as platforms for the generation of genetic vaccines against both DNA and RNA viruses. Mice vaccinated with such vectors encoding structural proteins from both foot-and-mouth disease virus and rotavirus were partially protected from challenge with wild-type virus (D'Antuono et al. Vaccine 28: 7363-7372, 2010; Laimbacher et al. Mol Ther 20: 1810-1820, 2012), indicating that HSV-1 amplicon vectors are attractive tools for the development of complex and safe genetic vaccines. This chapter describes the use of HSV-1 amplicon vectors that encode individual or multiple viral structural proteins from a polycistronic transgene cassette in mammalian cells. More precisely, amplicon vectors that encode multiple structural viral proteins support the in situ production of viruslike particles (VLPs) in vector-infected cells. The expression of the viral genes is confirmed by Western blot and immune fluorescence analysis, and the generation of VLPs in vector-infected cells is demonstrated by electron microscopy.

Evaluation of the immunogenicity of a recombinant HSV-1 vector expressing human group C rotavirus VP6 protein

“…Amplicon plasmid was constructed using the previously described pHSVs system (D'Antuono et al, 2010;Laimbacher and Fraefel et al, 2014). Briefly, the transgene expression is supported by the HSV-1 IE4/ 5 promoter, followed by a viral internal ribosomal entry site (IRES) which controls the EGFP reporter gene expression.…”

“…HSV-1 amplicon vectors have a large transgene capacity (up to 150 kbp), which allows the encapsidation of multiple genes or multiple copies of a transgene. Moreover, these vectors present (i) low toxicity and immunogenicity, (ii) high in vivo transduction efficiencies, both in quiescent and proliferating cells from most mammalian species including antigen presenting cells, (iii) genetic stability, and (iv) strong adjuvant effects inducing both humoral and cellular immune responses as well as mucosal immunity (de Silva and Bowers, 2009;Epstein, 2009;Laimbacher and Fraefel et al, 2014).…”

Genetic and subunit vaccines based on the stem domain of the equine influenza hemagglutinin provide homosubtypic protection against heterologous strains

“…The nucleotide sequence of the VP6 gene reported in this study was submitted to GenBank, and the assigned accession number is MF422080. et al, 2010;Laimbacher and Fraefel, 2014). Briefly, the transgene expression is supported by the HSV-1 IE4/5 promoter, followed by a viral internal ribosomal entry site (IRES) which controls the EGFP reporter gene expression.…”

“…Amplicon vector stocks were prepared as previously described (Laimbacher et al, 2012;Laimbacher and Fraefel, 2014;Oliveira et al, 2008;Saeki et al, 2001).…”

“…(up to 150 kbp), which allows the encapsidation of multiple genes or multiple copies of a transgene. Moreover, these vectors present (i) low toxicity and immunogenicity, (ii) high in vivo transduction efficiencies, both in quiescent and proliferating cells from most mammalian species including antigen presenting cells, (iii) genetic stability, and (iv) strong adjuvant effects inducing both humoral and cellular immune responses as well as mucosal immunity (de Silva and Bowers, 2009;Epstein, 2009;Laimbacher and Fraefel, 2014).…”