Peptide amphiphile micelles as a vaccine platform for Streptococcus pyogenes

摘要

Streptococcus pyogenes (Group A Streptococcus, GAS) frequently elicits diseases that range in severity from mild infections of the pharyngeal mucosa and demnis to life-threatening invasive diseases such as necrotizing fasciitis, impetigo, and toxic shock. Epidemiological studies estimate that each year greater than 500,000 worldwide deaths are attributable to GAS infections, placing it among the top ten leading causes of death from infectious pathogens. In the United States alone, more than $600 million is spent annually treating diseases caused by this organism with no effective preventative method established short of prophylactic antibiotic usage. Vaccines against GAS remain unavailable despite decade's worth of research and development. While whole-killed and live-attenuated vaccines have been tremendously effective in preventing pathogenic infections, they are also associated with undesirable side effects. Subunit vaccines that deliver just the peptide antigen of interest have been shown capable of stimulating an immune response. But these peptide antigens are generally weak immunogens on their own. In order to enhance the immunogenicity of peptide vaccines, new delivery systems must be designed. Peptide amphiphiles are unique biomaterials comprised of peptide-lipid conjugates that have been shown capable of delivering biologically active peptides for a variety of applications. Therefore, peptide amphiphile micelles provide a novel platform to improve the host immune response to peptide vaccines. The J8 peptide is a 29 amino acid B cell epitope that has been shown to generate an opsonophagocytic, high titer antibody response in mice. J8 was covalently tethered to a di-palmitic acid tail (J8-diC16) and fabricated into peptide amphiphile micelles in PBS. When delivered to mice subcutaneously, J8-diC16 was found to induce J8-spedfic high antibody liters greater than soluble J8 delivered with commercially available adjuvants. The research presented here demonstrates the promise peptide amphiphile micelles have in improving the field of vaccine engineering.