Antigen folding improves loading efficiency and antitumor efficacy of PC7A nanoparticle vaccine

Jonathan Wilhelm, Manuel Quiñones-Pérez, Jian Wang, Xu Wang, Vijay S. Basava, Jinming Gao

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Cancer vaccines hold great promise to produce antigen-specific T cell immunity for personalized therapy of cancer. Previously, we reported an ultra-pH-sensitive nanoparticle, PC7A, capable of priming an efficacious immune response without significant systemic toxicity. Despite the early success, the relationship between antigen properties and encapsulation efficiency for downstream immune activation remains poorly understood. In this study, we investigated a small library of melanoma antigens and the effects of several formulation methods on the efficiency of peptide loading inside PC7A nanoparticles. Results show loading efficiency is not highly dependent on the formulation methods, but instead mainly driven by the peptide antigen properties. In particular, we identified a phase transition event, namely the folding of antigenic peptides from random coils to α-helical structure, is important for antigen loading inside PC7A nanoparticles. Mutation of a peptide that abrogates the formation of helical structure resulted in poor loading efficiency. Antitumor efficacy studies in melanoma-bearing mice demonstrate the importance of peptide loading in vaccine-induced antitumor immunity. This study highlights the contribution of phase transition of peptide antigens on vaccine formulation in order to make widespread use of personalized nanoparticle vaccines feasible.

Original languageEnglish (US)
Pages (from-to)353-360
Number of pages8
JournalJournal of Controlled Release
Volume329
DOIs
StatePublished - Jan 10 2021

Keywords

  • Antigen delivery
  • Cancer vaccine
  • Peptide encapsulation
  • Secondary structure
  • Ultra-pH sensitive micelles

ASJC Scopus subject areas

  • Pharmaceutical Science

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