Proteogenomic characterization of the specific antibody repertoire induced by gold nanoparticles of differing shape and biomolecular surface: towards the development of nanoparticle-based vaccines

Abstract

Abstract Nanoparticles (NPs) in the size range of 1–100 nanometres (nm) present unique physical-chemical properties compared to bulk material making them suitable for a range of biomedical applications. Due to their size and shape, NPs engage in particular ways with cell receptors and by co-delivering antigens, adjuvants and immunomodulators grafter or encapsulated they can serve as new vaccine formulations for the treatment of several diseases such as cancer or HIV. Gold NPs (AuNPs) are interesting due to their ease of synthesis and control of size and shape, being the later considered a relevant parameter driving interactions with cell receptors. Here is shown the work to study the capabilities of AuNPs with different shape to induce antibody responses in vivo. Spherical and branched AuNPs were repeatedly inoculated subcutaneously to CD rats. The levels of Immunoglobulins G and M (IgG and IgM) were analyzed by Enzyme-Linked Immunosorbent assay (ELISA) and the B cell receptor (BCR) V(D)J rearrangements were assessed by Ig-Sequencing of the BCR transcripts from different lymphoid tissues. Mass spectrometry (MS) analysis of enriched IgG from treated rats plasma revealed the functional antibody response. In the case of branched AuNPs, the levels of total IgG and IgM appeared higher and increased autoantibody levels were found. V(D)J gene and allele usages were more diverse, showing considerable shifts in the repertoire, and B cell clonality was higher in comparison to spherical AuNPs and controls. Immune tolerance seems to be disrupted by branched NPs with particular biomolecular surfaces. These findings represent a step forwards in the development of NP-based vaccines towards motifs on the surface (e.g. tumor antigens) of such NPs.