Abstract
BackgroundHost-range restricted poxviruses make promising vaccine vectors due to their safety profile and immunogenicity. An understanding of the host innate immune responses produced by different poxvirus vectors would aid in the assessment, selection and rational design of improved vaccines for human and veterinary applications. Novel avipoxviruses are being assessed to determine if they are different from other poxvirus vectors. Analysis of the transcriptome induced in a mouse model would aid in determining if there were significant differences between different poxvirus vectors which may reflect different adjuvant potential as well as establish if they should be further evaluated as vaccine vectors.ResultsWe compared host transcript abundance in the spleens of BALB/c mice twenty four hours after intravenous infection (105 pfu/mouse) with six host-restricted poxvirus species from three genera, namely Lumpy Skin Disease virus (LSDV), Canarypox virus (CNPV), Fowlpox virus (FWPV), modified vaccinia Ankara (MVA) and two novel South African avipoxviruses, Feral Pigeonpox virus (FeP2) and Penguinpox virus (PEPV). These six viruses produced qualitatively and quantitatively distinct host responses with LSDV, followed by MVA, inducing the greatest interferon (IFN) response. FeP2 and PEPV caused very little change to host transcript abundance compared to the other 4 viruses tested. CNPV and FWPV induced the up regulation of two immunoglobulin genes (Ighg and Ighg3 (IgG3)) with CNPV inducing a third, Ighm (IgM). HIV-1–specific IgG3 antibodies have been correlated with decreased risk of HIV-1 infection in the RV144 trial, which included a CNPV-based vector (Yates et al. (Sci Transl Med, 6(228) p228, 2014). Up regulation of IgG3 by CNPV and FWPV but not the other poxviruses tested in vivo, implies that these two avipoxvirus-vector backbones may be involved in stimulation of the clinically important IgG3 antibody subclass. Differential transcript abundance associated with the different poxviruses is further discussed with particular emphasis on responses related to immune responses.ConclusionSix, genetically diverse host-restricted poxviruses produce different responses in a mouse model early after infection. These differences may affect the immune response induced to vaccine antigen in vectors based on these viruses. The two novel avipoxviruses were clearly distinguishable from the other viruses.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-1659-1) contains supplementary material, which is available to authorized users.
Highlights
Host-range restricted poxviruses make promising vaccine vectors due to their safety profile and immunogenicity
The poxviruses ALVAC, modified vaccinia Ankara (MVA) and NYVAC (both based on vaccinia virus (VACV) and have specific deletions) produce distinct innate immune profiles, characterised by different induction of pro-inflammatory and antiviral cytokines and chemokines in both rhesus monkeys and human PBMC [16]
Comparison of the host responses to different poxviruses We compared the differential host gene expression induced by six host-restricted poxviruses, MVA, lumpy skin disease virus (LSDV), Fowlpox virus (FWPV), Canarypox virus (CNPV), FeP2 and penguinpox virus (PEPV), in the spleens of BALB/c mice 24 h post infection
Summary
Host-range restricted poxviruses make promising vaccine vectors due to their safety profile and immunogenicity. An understanding of the host innate immune responses produced by different poxvirus vectors would aid in the assessment, selection and rational design of improved vaccines for human and veterinary applications. Host-range restricted poxviruses have been shown to successfully activate the host immune system [8, 9] and evidence exists that each virus does this in a different way, with an accompanying different pattern of transcript abundance [10,11,12,13,14,15]. The poxviruses ALVAC (based on canarypox virus), modified vaccinia Ankara (MVA) and NYVAC (both based on vaccinia virus (VACV) and have specific deletions) produce distinct innate immune profiles, characterised by different induction of pro-inflammatory and antiviral cytokines and chemokines in both rhesus monkeys and human PBMC [16]. Head to head comparisons of poxvirusvectored vaccines would help to establish the differences between the different vaccine vectors and the vaccineinduced response to achieve protection against pathogens and cancers
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