Peptide Amphiphile Micelle Vaccine Size and Charge Influence the Host Antibody Response

Vaccines are one of the best health care advances ever developed, having led to the eradication of smallpox and near eradication of polio and diphtheria. While tremendously successful, traditional vaccines (i.e., whole-killed or live-attenuated) have been associated with some undesirable side effects, including everything from mild injection site inflammation to the autoimmune disease Guillain-Barré syndrome. This has led recent research to focus on developing subunit vaccines (i.e., protein, peptide, or DNA vaccines) since they are inherently safer because they deliver only the bioactive components necessary (i.e., antigens) to produce a protective immune response against the pathogen of interest. However, a major challenge in developing subunit vaccines is overcoming numerous biological barriers to effectively deliver the antigen to the secondary lymphoid organs where adaptive immune responses are orchestrated. Peptide amphiphile micelles are a class of biomaterials that have been shown to possess potent self-adjuvanting vaccine properties, but their optimization capacity and underlying immunostimulatory mechanism are not well understood. The present work investigated the influence of micelle size and charge on the materials' bioactivity, including lymph node accumulation, cell uptake ability, and immunogenicity. The results generated provide considerable insight into how micelles exert their biological effects, yielding a micellar toolbox that can be exploited to either enhance or diminish host immune responses. This exciting development makes peptide amphiphile micelles an attractive candidate for both immune activation and suppression applications.