Engineered hybrid spider silk particles as delivery system for peptide vaccines

Lucke, Matthias; Mottas, Inès; Herbst, Tina; Hotz, Christian; Römer, Lin; Schierling, Martina B.; Herold, Heike M.; Slotta, Ute; Spinetti, Thibaud; Scheibel, Thomas; Winter, Gerhard; Bourquin, Carole; Engert, Julia

doi:10.1016/j.biomaterials.2018.04.008

Cited by 49 publications

(45 citation statements)

References 64 publications

(66 reference statements)

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“…In addition to PLGA, PPS, and LCP, many other materials have been fashioned into solid nanocarriers for immunotherapy: i) poly(lactide‐ co ‐hydroxymethylglycolic acid) as an analogous polyester to PLGA designed to overcome issues associated with acidification upon degradation, ii) PLGA–poly(ethylene glycol) (PEG) and polycaprolactone (PCL)–PEG conjugates, iii) copolymers based on N ‐(2‐hydroxypropyl)methacrylamide and poly( N ‐isopropylacrylamide) (PNIPAM), iv) polyanhydrides, v) polystyrene, and vi) silk, among others . The way in which these materials have been used varies broadly, underscoring the fact that no material is a “one size fits all” for delivering immunomodulatory payloads.…”

Section: Nanoscale Materials For Immunotherapymentioning

confidence: 99%

Materials for Immunotherapy

et al. 2019

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Breakthroughs in materials engineering have accelerated the progress of immunotherapy in preclinical studies. The interplay of chemistry and materials has resulted in improved loading, targeting, and release of immunomodulatory agents. An overview of the materials that are used to enable or improve the success of immunotherapies in preclinical studies is presented, from immunosuppressive to proinflammatory strategies, with particular emphasis on technologies poised for clinical translation. The materials are organized based on their characteristic length scale, whereby the enabling feature of each technology is organized by the structure of that material. For example, the mechanisms by which i) nanoscale materials can improve targeting and infiltration of immunomodulatory payloads into tissues and cells, ii) microscale materials can facilitate cell‐mediated transport and serve as artificial antigen‐presenting cells, and iii) macroscale materials can form the basis of artificial microenvironments to promote cell infiltration and reprogramming are discussed. As a step toward establishing a set of design rules for future immunotherapies, materials that intrinsically activate or suppress the immune system are reviewed. Finally, a brief outlook on the trajectory of these systems and how they may be improved to address unsolved challenges in cancer, infectious diseases, and autoimmunity is presented.

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Section: Nanoscale Materials For Immunotherapymentioning

confidence: 99%

Materials for Immunotherapy

et al. 2019

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“…The PADRE sequence was linked to the main domain of the vaccine construct using the Cathepsin S cleavable linker (PMGLP). In the human skin, the protease activity of cathepsin S has the main role in the antigen presentation pathways mediated by MHC class II molecules [101][102][103] . The details of the designed DPVC are captioned in Fig.…”

Section: Designing the Candidate Vaccine Constructsmentioning

confidence: 99%

Prophylactic domain-based vaccine against SARS-CoV-2, causative agent of COVID-19 pandemic

Pourseif

Parvizpour

Jafari

et al. 2020

Preprint

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Coronavirus disease 2019 (COVID-19) is undoubtedly the most challenging pandemic in the current century with more than 253,381 deaths worldwide since its emergence in late 2019 (updated May 6th, 2020). COVID-19 is caused by a novel emerged coronavirus named as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Today, the world needs crucially to develop a prophylactic vaccine scheme for such emerged and emerging infectious pathogens. In this study, we have targeted spike (S) glycoprotein, as an important surface antigen of SARS-CoV-2, to identify its immunodominant B- and T-cell epitopes. We have conducted a multi-method B-cell epitope (BCE) prediction approach using different predictor algorithms to discover most potential BCEs. Besides, we sought among a pool of MHC class I and II-associated peptide binders provided by the IEDB server through the strict cut-off values. To design a broad-coverage vaccine, we carried out a population coverage analysis for a set of candidate T-cell epitopes and based on the HLA allele frequency in the top most-affected countries by COVID-19 (update 02 April 2020). The final determined B- and T-cell epitopes were mapped on the S glycoprotein sequence, and three potential hub regions covering the largest number of overlapping epitopes were identified for the vaccine designing (I531–N711; T717–C877; and V883–E973). Here, we have designed two domain-based constructs to be produced and delivered through the recombinant protein- and gene-based approaches, including (i) an adjuvanted domain-based protein vaccine construct (DPVC), and (ii) a self-amplifying mRNA vaccine (SAMV) construct. The safety, stability, and immunogenicity of the DPVC were validated using the integrated sequential (i.e. allergenicity, autoimmunity, and physicochemical features) and structural (i.e. molecular docking between the vaccine and human Toll-like receptors (TLRs) 4 and 5) analysis. The stability of the docked complexes was evaluated using the molecular dynamics (MD) simulations. These rigorous in silico validations supported the potential of the DPVC and SAMV to promote both innate and specific immune responses in the animal studies.

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“…lms, hydrogels, bers, capsules and particles [2,4]. The versatility of silk proteins along with their biochemical properties make silk-derived materials potentially suitable for tissue engineering and regeneration as well as controllable delivery of protein drugs and peptide vaccines [5][6][7][8][9]. Due to di culties in breeding spiders and collecting silks, native spider silk is not economic and realistic to harvest on a large scale, while in nowadays recombinant production is becoming the main strategy for obtaining either spider silk protein (spidroin) or arti cial spider ber [10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

One-step heating strategy for efficient solubilization of recombinant spider silk protein from inclusion bodies

Cheng¹,

Chen

Yu³

et al. 2020

Preprint

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Abstract Background: Spider silk is a proteinaceous fiber with remarkable mechanical properties spun from spider silk proteins (spidroins). Engineering spidroins have been successfully produced in a variety of heterologous hosts and the most widely used expression system is Escherichia coli (E. coli). So far, recombinantly expressed spidroins often form insoluble inclusion bodies (IBs), which will often be dissolved under extremely harsh conditions in a traditional manner, e.g. either 8 mol/L urea or 6 mol/L guanidine hydrochloride, highly risking to poor recovery of bioactive proteins as well as unexpected precipitations during dialysis process. Results: Here, we present a mild solubilization strategy—one-step heating method to solubilize spidroins from IBs, with combining spidroins’ high thermal stability with low concentration of urea. A 430-aa recombinant protein (designated as NM) derived from the minor ampullate spidroin of Araneus ventricosus was expressed in E. coli, and the recombinant proteins were mainly present in insoluble fraction as IBs. The isolated IBs were solubilized parallelly by both traditional urea-denatured method and one-step heating method, respectively. The solubilization efficiency of NM IBs in Tris-HCl pH 8.0 containing 4 mol/L urea by one-step heating method was already comparable to that of 7 mol/L urea with using traditional urea-denatured method. The effects of buffer, pH and temperature conditions on NM IBs solubilization of one-step heating method were evaluated, respectively, based on which the recommended conditions are: heating temperature 70–90°C for 20 min, pH 7.0–10, urea concentration 2–4 mol/L in normal biological buffers. The recombinant NM generated via the one-step heating method held the potential functions with self-assembling into sphere nanoparticles with smooth morphology.Conclusions: The one-step heating method introduced here efficiently solubilizes IBs under relatively mild conditions compared to the traditional ones, which might be important for the downstream applications; however, this protocol should be pursued carefully in terms of urea-induced modification sensitive applications. Further, this method can be applied under broad buffer, pH and temperature conditions, conferring the potential to apply to other thermal stable proteins.

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Engineered hybrid spider silk particles as delivery system for peptide vaccines

Cited by 49 publications

References 64 publications

Materials for Immunotherapy

Materials for Immunotherapy

Prophylactic domain-based vaccine against SARS-CoV-2, causative agent of COVID-19 pandemic

One-step heating strategy for efficient solubilization of recombinant spider silk protein from inclusion bodies

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