VLV (virus like vaccine): ERV (endogenous retrovirus)。ERVはヒトの内在性ウイルスでゲノムの8%を占めています。通常細胞では不活性状態ですが、いくつかのガンで検出されます。
目的タンパク質
免疫の賦活化対象をERVと目的タンパク質の両方に向ける戦略
Congratulations to partner InProTher on their published article discussing the potential of #adenovirus to target endogenous retroviruses (ERVs) and help fight diseases including #cancer. Our licensing agreement with InProTher includes coverage of SIRION’s adenovirus technologies to cancer #vaccines encoding ERV-derived antigens for active #immunotherapy. https://bit.ly/2Zn4d72 #viralvectors
Figure 2
Illustration of the immune responses elicited by adenovirus based virus-like-vaccine (VLV) vaccination encoding endogenous retroviral (ERV) genes.
(1)
Vaccination with the adenoviral vector (Ad) encoding GAG and ENV genes, ideally harbouring mutations in the immunosuppressive domain (ISD) of ENV, is injected.
(2)
At the site of injection Ad directly infects professional antigen presenting cells (APCs) and releases the transgene into the recipient cell nucleus. (3)
In the nucleus, the viral DNA codes for both viral and transgene proteins. Following their production, the fate of these proteins can be:
(4)
release of virus-like-particles (VLP)s to stimulate B-cells in an antigen structure dependent way;
(5)
uptake by APCs for endosomal degradation, presentation on major histocompatibility complex class II molecules (MHC-II), or
(6)
degradation in the proteasome (directly or after uptake) for presentation on major histocompatibility complex class I molecules (MHC-I)
(7)
stimulation of CD4+ T-cells and subsequent B-cell stimulation, and stimulation of CD8+ T-cells.
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