Nanovaccines for listeriosis

Since many years there has been an urgent need for an effective and safe vaccine against listeriosis. Conventional vaccination strategies using recombinant antigens or killed bacteria have been abandoned as they failed to induce significant T-cell responses required for protection. Likewise, the risk for immune-compromised individuals discarded the use of live bacteria.

Our laboratory has designed a different approach to solve this problem, the use of cellular vaccines as vectors to deliver antigens. In this regard, dendritic cell vaccines loaded ex vivo with Listeria monocytogenes GAPDH1-22 peptide from glyceraldehyde-3-phosphate-dehydrogenase provided great results, as they induced significant T-cell immunity and protection in animal models. However, this kind of vaccines seemed difficult and expensive to prepare, so we need better options to obtain affordable vaccines for clinical use.

Nanomedicine has emerged as a versatile tool to develop vaccines and antibacterial agents. Gold glyconanoparticles (GNP) are perfect candidates for vaccine vectors as they are easy to handle, resistant to enzymatic degradation, water soluble, non-toxic, presented small size, can be loaded with antigens and targeted to immune cells. Therefore, we used GNPs to prepare a Listeria based nanovaccine, loaded with the lysteriolysin O peptide LLO91-99 (GNP-LLO) and formulated with a novel polysaccharide adjuvant based on delta inulin (Advax™).

GNP-LLO91-99 formulated with Advax™ induced robust Listeria-specific CD4+ and CD8+ T-cell responses and conferred listeriosis protection. Listeriosis protection correlated with increased frequencies of splenic CD4+ and CD8+ T cells, NK cells and CD8a+ dendritic cells, as well as with a Th1 cytokine pattern, producing significant levels of IL-12, IFN-g, TNF-a, and MCP-1.

This novel approach offers the first opportunity to produce a cheap and reliable Listeria vaccine to use as conventional prophylactic vaccine for all fellows at risk of listeriosis.