Development of a Peptide Hydrogel for a Slow-Release HIV-1 Vaccination System

Authors

  • AS Carson
  • C Cheng
  • C Jenkins
  • Y Tsybovsky
  • A Biju
  • TC Pierson

Abstract

HIV-1 persists as a serious threat to global health, making the development of a vaccine that can induce broadly neutralizing antibodies against the virus paramount. Epitope-based vaccine designs have emerged as a strategy to focus the humoral immune response on specific vulnerable targets on the HIV-1 Env protein surface, including the HIV-1 fusion peptide (FP). To further potentiate the humoral response, slow-release immunization methods have been developed to increase germinal center immunogen processing and promote antibody somatic hypermutation. To this end, we developed a peptide hydrogel, capable of self-assembly into nanofibers. The peptide consists of HIV-1 FP joined to an amphipathic peptide. Hydrophilic and hydrophobic interactions potentially allow the amphipathic peptides to stack, resulting in a higher structure with FP extended and exposed into solution. The hydrogel is designed to disassemble over time, releasing individual peptides, and eliciting a FP-specific response. The designed hydrogel peptide is recognized by FP-directed monoclonal antibodies, indicating that the FP is present in the correct conformation. Negative stain-electron microscopy studies determine that the peptide hydrogel forms nanofibers and other higher-order structures when present at concentrations between 1 mg/mL-20 mg/mL, in the presence or absence of the adjuvant 3M052/Alum. Following these results, we are proceeding with a guinea pig animal study to evaluate whether the FP hydrogel vaccine elicits a more robust and effective neutralizing humoral response than traditional protein immunizations.

Scientific Focus Area: Immunology

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