New cancer vaccine strategies are required to vanquish the self-tolerance and elicit robust immune responses against tumor-associated antigens and/or neoantigens. Contemporary approaches in nanomedicine center on the use of single nanocarriers modified with multiple copies of multiple different functional domains, e.g. epitopes for vaccines. The application of single nanocarriers however stands in contrast to other therapeutic strategies, for example antibodies are often given as cocktails, phage therapy is based on a cocktail of phages. Therefore, we set out to develop a combinatorial approach toward the next generation concept of epitope delivery; a prime-boost strategy in which the same epitope is being delivered using different nanocarriers. We use plant viral nanoparticles and virus-like particles (VLPs) thereof as the nanoplatform to deliver cancer-associated antigens; integration of the epitopes is achieved through bioconjugation. Repeated vaccination of the VLP vaccines induced different immune responses (Th2 vs Th1). The heterologous prime boost strategy using a sequential combination of nanocarriers induced higher IgG titers against the target epitope. More importantly, the recognition and cytotoxicity of the antisera to cancer cells were significantly enhanced resulting in extended survival when given as therapeutic vaccine to mice bearing tumors. This work provides a novel strategy to activate the immune system and elicit robust immune response against low immunogenic antigens. In principal, this method can be used for other antigens related to cancer and infectious diseases.<br/>

Epitope display and delivery using plant VLPs: Concept of prime-boost immunization

2019 Fall National Meeting

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