Stimulation of the immune system by a tumor antigen-bearing adenovirus-inspired VLP allows control of melanoma growth

Virus-like particles (VLPs) are versatile protein-based platforms that can be used as a vaccine platform mainly in infectiology. In the present work, we compared a previously designed, non-infectious, adenovirus-inspired 60-mer dodecahedric VLP to display short epitopes or a large tumor model antigen. To validate these two kinds of platforms as a potential immunostimulating approach, we evaluated their ability to control melanoma B16-ovalbumin (OVA) growth in mice. A set of adjuvants was screened, showing that polyinosinic-polycytidylic acid (poly(I:C)) was well suited to generate a homogeneous cellular and humoral response against the desired epitopes. In a prophylactic setting, vaccination with the VLP displaying these epitopes resulted in total inhibition of tumor growth 1 month after vaccination. A therapeutic vaccination strategy showed a delay in grafted tumor growth or its total rejection. If the simple epitope display on the VLP is sufficient to prevent tumor growth, then an improved engineered platform enabling display of a large antigen is a tool to overcome the barrier of immune allele restriction, broadening the immune response, and paving the way for its potential utilization in humans as an off-the-shelf vaccine.

Automated summary

This study compared a protein-based virus-like particle (VLP) platform capable of displaying short epitopes or large tumor antigens, and evaluated their effectiveness against melanoma. The VLP displaying short epitopes completely inhibited tumor growth, while an improved platform displaying large antigens overcame immune allele restriction, broadening the immune response and paving the way for its potential use as an off-the-shelf vaccine in humans.