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.
Highlights
Vaccines that induce Cytotoxic T lymphocyte (CTL) responses are important prophylactic or therapeutic modules against cancer and infectious diseases.[1,2,3] Using carriers to promote these vaccines’ delivery to antigen presenting cells is a strategy to enhance the potency of the vaccines.[4, 5] While various natural and synthetic materials have been tested as building materials of CTL vaccine carriers,(6, 7) among them, only virus-like particles (VLPs) have been approved for clinical use to facilitate CTL responses,(5) a contrast suggesting a need to further search for suitable vaccine carrier materials.Elastin-like polypeptides (ELPs) share the same chemical nature, protein, with VLPs
ELPs are a promising type of CTL vaccine carriers
(1) The protein-or peptide-based CTL vaccines, potentially, can be fused together with ELPs using genetic engineering approach; the resultant fusion proteins may be reproduced in E.coli or other expression systems similar to some existing ELP fusions.[9, 10] [2] When the vaccines are loaded to the carriers using the genetic engineering approach, the copy numbers of the vaccines and their cleavage sites from the carriers are well defined and precisely adjusted to improve the potency of vaccines.[11,12,13] [3] The signature property of ELP – the reversible, thermally-induced, inverse phase transition – is transferable to ELP-protein fusions and possibly to immune-tolerant elastin-like polypeptide (iTEP)-vaccine fusions;(14) The fusions can be purified by cycling the transition
Summary
Vaccines that induce CTL responses are important prophylactic or therapeutic modules against cancer and infectious diseases.[1,2,3] Using carriers to promote these vaccines’ delivery to antigen presenting cells is a strategy to enhance the potency of the vaccines.[4, 5] While various natural and synthetic materials have been tested as building materials of CTL vaccine carriers,(6, 7) among them, only virus-like particles (VLPs) have been approved for clinical use to facilitate CTL responses,(5) a contrast suggesting a need to further search for suitable vaccine carrier materials.Elastin-like polypeptides (ELPs) share the same chemical nature, protein, with VLPs. [1] The protein-or peptide-based CTL vaccines, potentially, can be fused together with ELPs using genetic engineering approach; the resultant fusion proteins may be reproduced in E.coli or other expression systems similar to some existing ELP fusions.[9, 10] [2] When the vaccines are loaded to the carriers using the genetic engineering approach, the copy numbers of the vaccines and their cleavage sites from the carriers are well defined and precisely adjusted to improve the potency of vaccines.[11,12,13] [3] The signature property of ELP – the reversible, thermally (or ion)-induced, inverse phase transition – is transferable to ELP-protein fusions and possibly to iTEP-vaccine fusions;(14) The fusions can be purified by cycling the transition Having these appealing features, ELPs have not been reported as CTL vaccine carriers to date.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
