Peptide subunit vaccines are desirable because they increase control over the induced immune response and safety of a vaccine by reducing the risk of off-target responses. The immunogenicity of most peptides, however, is often insufficient to produce robust and lasting immunity. Many materials and delivery vehicles have been developed to incorporate target antigens to improve the induced immune response while maintaining specificity and control. We have developed peptide nanoclusters (PNCs) as a subunit peptide vaccine formulation that has shown potential to increase immunogenicity of peptide subunit vaccines. PNCs are comprised of crosslinked peptide antigen, and have been successfully synthesized from several therapeutically relevant peptides as small as 8 amino acids in length. However, synthesis of the PNCs requires either adding residues to the peptide epitope sequence or engaging amino acids within the antigen epitope in conjugation chemistry to form a stable material with sufficient antigen incorporation. It is important to understand if and how these modifications and the stability of the crosslinking itself affect immune responses to inform the formulation of peptide vaccines for induction of the desired immune response with a wide variety of peptide antigens. To understand the effects of peptide sequence and crosslinking, several types of PNCs were synthesized by desolvation from the model peptide epitope SIINFEKL, which is derived from the immunogenic protein ovalbumin. In some variations, SIINFEKL was altered to include extra residues on each end strategically chosen to enable more conjugation chemistry options, as well as to increase the size of the peptide beyond the minimal presented epitope. Additionally, both reversible and irreversible crosslinkers were used to form the PNCs. These variations were evaluated for immune cell responses in vitro. Dendritic cell antigen presentation and antigen-specific T cell activation depended on the type of peptide formulation. Further, dendritic cell presentation did not always correlate with strong T cell activation. These results, as well as those of in vivo immunization with the PNC variants will be discussed. The knowledge gained in this work will be applied to disease-specific PNC synthesis to maximize immunogenicity and, ultimately, efficacy of peptide subunit vaccines.

Peptide nanocluster vaccine formulation impacts immune response

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.