Immune-tolerant elastin-like polypeptides (iTEPs) and their application as CTL vaccine carriers

Abstract

Background: Cytotoxic T lymphocyte (CTL) vaccine carriers are known to enhance the efficacy of vaccines, but a search for more effective carriers is warranted. Elastin-like polypeptides (ELPs) have been examined for many medical applications but not as CTL vaccine carriers.

Purpose: We aimed to create immune tolerant ELPs using a new polypeptide engineering practice and create CTL vaccine carriers using the ELPs.

Results: Four sets of novel ELPs, termed immune-tolerant elastin-like polypeptide (iTEP) were generated according to the principles dictating humoral immunogenicity of polypeptides and phase transition property of ELPs. The iTEPs were non-immunogenic in mice. Their phase transition feature was confirmed through a turbidity assay. An iTEP nanoparticle (NP) was assembled from an amphiphilic iTEP copolymer plus a CTL peptide vaccine, SIINFEKL. The NP facilitated the presentation of the vaccine by dendritic cells (DCs) and enhanced vaccine-induced CTL responses.

Discussion: A new ELP design and development practice was established. The non-canonical motif and the immune tolerant nature of the iTEPs broaden our insights about ELPs. ELPs, for the first time, were successfully used as carriers for CTL vaccines.

Conclusion: It is feasible to concurrently engineer both immune-tolerant and functional peptide materials. ELPs are a promising type of CTL vaccine carriers.

• Cytotoxic T lymphocyte (CTL) vaccine
• immune-tolerant elastin-like polypeptide
• inverse phase transition
• non-canonical elastin-like polypeptide motifs
• reversible
• vaccine carrier
• thermally-induced

Acknowledgements

The authors thank Dr. Sung Wan Kim for the DLS measurements in his lab. Dr. James Marvin and Chris Leukel at the University of Utah Flow Cytometry Core provided technical assistance. The authors would also express their appreciation to Dr. Andrew Ramstead for his comments and suggestions on the manuscript, Dr. Kenneth Rock for DC2.4 cells, and Dr. Nilabh Shastri for B3Z cells.

Declaration of interest

The work is supported by the University of Utah Start-up Fund, University of Utah Seed Grant, and NIH R00CA153929 to M.C.

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Supplementary material available online

Supplementary Figure S1 and Table S1