title: A Comparison Study of iTEP Nanoparticle-Based CTL Vaccine Carriers Revealed a Surprise Relationship between the Stability and Efficiency of the Carriers.
abstract: Vaccine carriers have been shown to enhance cytotoxic T lymphocyte (CTL) epitope peptide vaccines by addressing intrinsic limitations of the vaccines. We have previously developed an immune-tolerant elastin-like polypeptide (iTEP)-based nanoparticle (NP) as an effective and unique CTL vaccine carrier. The NP is unique for its humoral immune tolerance, flexible structure, and ability to deliver CTL vaccines as polypeptide fusions. Here, we aimed to improve the NP by increasing its stability since we found it was not stable. We thus generated a more stable iTEP NP (ST-NP) and used it to deliver a CTL peptide vaccine, SIINFEKL. However, we surprisingly found that the ST-NP had a lower efficiency than the previously developed, marginally stable iTEP NP (MS-NP) in terms of promoting vaccine presentation and vaccine-induced CTL responses. On the other hand, dendritic cells (DCs) showed preferential uptake of the ST-NP but not the MS-NP. To develop an iTEP vaccine carrier that outperforms both the MS-NP and the ST-NP, we devised an iTEP NP that has a changeable stability responsive to a cytosolic, reductive environment, termed reductive environment-dependent NP or RED-NP. The RED-NP showed an intermediate ability to promote vaccine presentation and T cell responses in vitro between the MS-NP and the ST-NP. However, the RED-NP induced the strongest CTL responses in vivo among all three NPs. In conclusion, iTEP NPs that have a dynamically changeable stability are most effective to deliver and enhance CTL peptide vaccines. The work also demonstrated the versatile nature of iTEP vaccine carriers.
authors.affiliation: 1. Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, Utah 84112, U.S.A.
authors.forename: Shuyun
authors.initials: S
authors.lastname: Dong
authors.affiliation: 2. Cancer Institute of Hainan Medical College, Affiliated Hospital of Hainan Medical College, Haikou City, Hainan Province 570102, China.
authors.forename: Tiefeng
authors.initials: T
authors.lastname: Xu
authors.affiliation: 1. Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, Utah 84112, U.S.A.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhao
authors.affiliation: 3. Dept. of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824, U.S.A.
authors.forename: Kristin N
authors.initials: KN
authors.lastname: Parent
authors.affiliation: 1. Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, Utah 84112, U.S.A.
authors.forename: Mingnan
authors.initials: M
authors.lastname: Chen
mesh_terms: D000818:Animals; D002460:Cell Line; D003713:Dendritic Cells / Q000276:immunology; D004337:Drug Carriers / Q000008:administration & dosage*; D004355:Drug Stability; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D022223:Vaccines, Subunit / Q000008:administration & dosage* / Q000276:immunology*
chemical_list: D004337:Drug Carriers; D022223:Vaccines, Subunit
keywords: Cytotoxic T lymphocyte (CTL) vaccine; changeable carrier stability; iTEP nanoparticle; vaccine processing.