Construction and characterisation of replicating foamy viral vectors expressing HIV-1 epitopes recognised by broadly neutralising antibodies

Mühle, Michael; Hoffmann, Kerstin; Löchelt, Martin; Denner, Joachim

doi:10.1016/j.antiviral.2013.09.009

Cited by 3 publications

(1 citation statement)

References 48 publications

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“…The suitability of FVs as replication-deficient gene therapy vectors for long-term protein expression has been demonstrated in a dog model [ 28 – 30 ]. Several studies have also shown that antibodies were generated against heterologous B cell epitopes displayed by feline foamy virus (FFV) particles or proteins [ 17 , 31 , 32 ]. Experimental infections of large animals have not led to vector-related pathogenesis, indicating that FVs are suitable for long-term protein, antigen or epitope expression in host cells [ 17 , 27 ].…”

Section: Introductionmentioning

confidence: 99%

Replication-Competent Foamy Virus Vaccine Vectors as Novel Epitope Scaffolds for Immunotherapy

et al. 2015

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The use of whole viruses as antigen scaffolds is a recent development in vaccination that improves immunogenicity without the need for additional adjuvants. Previous studies highlighted the potential of foamy viruses (FVs) in prophylactic vaccination and gene therapy. Replication-competent FVs can trigger immune signaling and integrate into the host genome, resulting in persistent antigen expression and a robust immune response. Here, we explored feline foamy virus (FFV) proteins as scaffolds for therapeutic B and T cell epitope delivery in vitro. Infection- and cancer-related B and T cell epitopes were grafted into FFV Gag, Env, or Bet by residue replacement, either at sites of high local sequence homology between the epitope and the host protein or in regions known to tolerate sequence alterations. Modified proviruses were evaluated in vitro for protein steady state levels, particle release, and virus titer in permissive cells. Modification of Gag and Env was mostly detrimental to their function. As anticipated, modification of Bet had no impact on virion release and affected virus titers of only some recombinants. Further evaluation of Bet as an epitope carrier was performed using T cell epitopes from the model antigen chicken ovalbumin (OVA), human tyrosinase-related protein 2 (TRP-2), and oncoprotein E7 of human papillomavirus type 16 (HPV16E7). Transfection of murine cells with constructs encoding Bet-epitope chimeric proteins led to efficient MHC-I-restricted epitope presentation as confirmed by interferon-gamma enzyme-linked immunospot assays using epitope-specific cytotoxic T lymphocyte (CTL) lines. FFV infection-mediated transduction of cells with epitope-carrying Bet also induced T-cell responses, albeit with reduced efficacy, in a process independent from the presence of free peptides. We show that primate FV Bet is also a promising T cell epitope carrier for clinical translation. The data demonstrate the utility of replication-competent and -attenuated FVs as antigen carriers in immunotherapy.

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Section: Introductionmentioning

confidence: 99%

Replication-Competent Foamy Virus Vaccine Vectors as Novel Epitope Scaffolds for Immunotherapy

et al. 2015

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Epitope Mapping of the Antibody Response Against the Envelope Proteins of the Feline Foamy Virus

et al. 2017

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Foamy viruses (FV) are retroviruses that infect several species without pathological signs, but induce substantial antibody responses in the infected host. In the case of feline FV (FFV), antibodies against Gag, Bet, and Env have been used to indicate infection; however, it is unclear whether the response to specific epitopes correlates with immunity. Here, we investigated the epitope specificity of antibodies targeting the Env protein using peptide microarrays. Sera from naturally and experimentally FFV-infected cats and pumas and from rats immunized with FFV Env expression plasmids were analyzed. An immunodominant epitope was identified in the Env leader protein (Elp), and a strong reactivity to two epitope clusters in the transmembrane (TM) subunit of Env was observed. Moreover, a short stretch of residues in the C-terminal part of the surface (SU) protein was found to be significantly associated with FFV serotype FUV-mediated neutralization. Taken together, our results add a new level of detail on the B cell epitope repertoire induced during FFV infection. Furthermore, our results provide a basis for current attempts to modify FV vectors to express and present vaccine epitopes for the directed induction of humoral immunity.

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HIV-1 vaccine epitope delivery based on foamy viral hybrid proteins and vectors

Mühle¹

2015

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Construction and characterisation of replicating foamy viral vectors expressing HIV-1 epitopes recognised by broadly neutralising antibodies

Cited by 3 publications

References 48 publications

Replication-Competent Foamy Virus Vaccine Vectors as Novel Epitope Scaffolds for Immunotherapy

Replication-Competent Foamy Virus Vaccine Vectors as Novel Epitope Scaffolds for Immunotherapy

Epitope Mapping of the Antibody Response Against the Envelope Proteins of the Feline Foamy Virus

HIV-1 vaccine epitope delivery based on foamy viral hybrid proteins and vectors

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