Self-Assembling Peptides for Vaccine Development and Antibody Production

  • Zhongyan Wang
  • Youzhi Wang
  • Jie Gao
  • Yang ShiEmail author
  • Zhimou YangEmail author
Living reference work entry


Self-assembling peptides have shown great potential for drug delivery, cancer cell inhibition, and regenerative medicine. Recently studies indicate that they are also promising for subunit vaccine delivery. We summarize in this tutorial review two strategies to deliver subunit vaccines, one by covalently conjugating and the other one by physically mixing. By the former strategy, protein and peptide antigens are covalently connected with self-assembling peptides, and the resulting peptides can self-assemble into nanofibers by themselves or by mixing with the original self-assembling peptides. For the latter one, antigens including DNA, proteins, and attenuated cells physically interact with nanofibers of self-assembling peptides via charge interaction, hydrogen bonding, hydrophobic interaction, etc. Both strategies can prolong the lifetime of subunit vaccines at injection sites, assist antigen uptake by antigen-presenting cells (APCs), facilitate transportation of antigens from injection sites to lymph nodes, and stimulate downstream immune responses. Vaccines based on self-assembling peptides can raise stronger antibody productions, which is useful for protective vaccine development and antibody production. Besides, several vaccines capable of eliciting strong CD8+ T-cell response are also introduced in this paper, and they are promising for the development of vaccines to treat important diseases such as cancers and HIV. Challenges remained are also discussed in the last section of the paper. Overall, self-assembling peptides are very useful for antibody production and the development of novel vaccines to treat important diseases.


  1. 1.
    Plotkin SA (2005) Vaccines: past, present and future. Nat Med 11:S5–S11CrossRefPubMedGoogle Scholar
  2. 2.
    Rappuoli R, Aderem A (2011) A 2020 vision for vaccines against HIV, tuberculosis and malaria. Nature 473:463–469CrossRefPubMedGoogle Scholar
  3. 3.
    Germain RN (2010) Vaccines and the future of human immunology. Immunity 33:441–450CrossRefPubMedGoogle Scholar
  4. 4.
    Reed SG, Bertholet S, Coler RN et al (2009) New horizons in adjuvants for vaccine development. Trends Immunol 30:23–32CrossRefPubMedGoogle Scholar
  5. 5.
    Bachmann MF, Jennings GT (2010) Vaccine delivery: a matter of size, geometry, kinetics and molecular patterns. Nat Rev Immunol 10:787–796CrossRefPubMedGoogle Scholar
  6. 6.
    Goldberg MS (2015) Immunoengineering: how nanotechnology can enhance cancer immunotherapy. Cell 161:201–204CrossRefPubMedGoogle Scholar
  7. 7.
    Hu C-MJ, Fang RH, Luk BT et al (2013) Nanoparticle-detained toxins for safe and effective vaccination. Nat Nanotechnol 8:933–938CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Moon JJ, Suh H, Bershteyn A et al (2011) Interbilayer-crosslinked multilamellar vesicles as synthetic vaccines for potent humoral and cellular immune responses. Nat Mater 10:243–251CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Collier JH, Rudra JS, Gasiorowski JZ et al (2010) Multi-component extracellular matrices based on peptide self-assembly. Chem Soc Rev 39:3413–3424CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Du X, Zhou J, Shi J et al (2015) Supramolecular hydrogelators and hydrogels: from soft matter to molecular biomaterials. Chem Rev 115:13165–13307CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Ulijn RV (2015) Molecular self-assembly. Best of both worlds. Nat Nanotechnol 10:295–296CrossRefPubMedGoogle Scholar
  12. 12.
    Zelzer M, Ulijn RV (2010) Next-generation peptide nanomaterials: molecular networks, interfaces and supramolecular functionality. Chem Soc Rev 39:3351–3357CrossRefPubMedGoogle Scholar
  13. 13.
    Versluis F, van Esch JH, Eelkema R (2016) Synthetic self-assembled materials in biological environments. Adv Mater 28:4576–4592CrossRefPubMedGoogle Scholar
  14. 14.
    Tao K, Levin A, Adler-Abramovich L et al (2016) Fmoc-modified amino acids and short peptides: simple bio-inspired building blocks for the fabrication of functional materials. Chem Soc Rev 45:3935–3953CrossRefPubMedGoogle Scholar
  15. 15.
    Yuan Y, Wang L, Du W et al (2015) Intracellular self-assembly of Taxol nanoparticles for overcoming multidrug resistance. Angew Chem Int Ed 54:9700–9704CrossRefGoogle Scholar
  16. 16.
    Zhao F, Ma ML, Xu B (2009) Molecular hydrogels of therapeutic agents. Chem Soc Rev 38:883–891CrossRefPubMedGoogle Scholar
  17. 17.
    Luo Z, Zhang S (2012) Designer nanomaterials using chiral self-assembling peptide systems and their emerging benefit for society. Chem Soc Rev 41:4736–4754CrossRefPubMedGoogle Scholar
  18. 18.
    Boekhoven J, Stupp SI (2014) 25th anniversary article. Supramolecular materials for regenerative medicine. Adv Mater 26:1642–1659CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Wang Y, Cheetham AG, Angacian G et al (2017) Peptide–drug conjugates as effective prodrug strategies for targeted delivery. Adv Drug Deliver Rev 110:112–126CrossRefGoogle Scholar
  20. 20.
    Wen Y, Collier JH (2015) Supramolecular peptide vaccines: tuning adaptive immunity. Curr Opin Immunol 35:73–79CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Rudra JS, Tian YF, Jung JP et al (2010) A self-assembling peptide acting as an immune adjuvant. Proc Natl Acad Sci 107:622–627CrossRefPubMedGoogle Scholar
  22. 22.
    Chen J, Pompano RR, Santiago FW et al (2013) The use of self-adjuvanting nanofiber vaccines to elicit high-affinity B cell responses to peptide antigens without inflammation. Biomaterials 34:8776–8785CrossRefPubMedGoogle Scholar
  23. 23.
    Rudra JS, Mishra S, Chong AS et al (2012) Self-assembled peptide nanofibers raising durable antibody responses against a malaria epitope. Biomaterials 33:6476–6484CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Rudra JS, Sun T, Bird KC et al (2012) Modulating adaptive immune responses to peptide self-assemblies. ACS Nano 6:1557–1564CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Hudalla GA, Sun T, Gasiorowski JZ et al (2014) Gradated assembly of multiple proteins into supramolecular nanomaterials. Nat Mater 13:829CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Cui H, Webber MJ, Stupp SI (2010) Self-assembly of peptide amphiphiles: from molecules to nanostructures to biomaterials. Biopolymers 94:1–18CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Zhu X, Ramos TV, Gras-Masse H et al (2004) Lipopeptide epitopes extended by an Nϵ-palmitoyl-lysine moiety increase uptake and maturation of dendritic cells through a toll-like receptor-2 pathway and trigger a Th1-dependent protective immunity. Eur J Immunol 34:3102–3114CrossRefPubMedGoogle Scholar
  28. 28.
    Black M, Trent A, Kostenko Y et al (2012) Self-assembled peptide Amphiphile micelles containing a cytotoxic T-cell epitope promote a protective immune response in vivo. Adv Mater 24:3845–3849CrossRefPubMedGoogle Scholar
  29. 29.
    Manolova V, Flace A, Bauer M et al (2008) Nanoparticles target distinct dendritic cell populations according to their size. Eur J Immunol 38:1404–1413CrossRefPubMedGoogle Scholar
  30. 30.
    Singh A, Peppas NA (2014) Hydrogels and scaffolds for immunomodulation. Adv Mater 26:6530–6541CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Bencherif SA, Sands RW, Ali OA et al (2015) Injectable cryogel-based whole-cell cancer vaccines. Nat Commun 6:7556Google Scholar
  32. 32.
    Medina SH, Li S, Howard OZ et al (2015) Enhanced immunostimulatory effects of DNA-encapsulated peptide hydrogels. Biomaterials 53:545–553CrossRefPubMedGoogle Scholar
  33. 33.
    Tian Y, Wang H, Liu Y et al (2014) A peptide-based nanofibrous hydrogel as a promising DNA nanovector for optimizing the efficacy of HIV vaccine. Nano Lett 14:1439–1445CrossRefPubMedGoogle Scholar
  34. 34.
    Wang H, Luo Z, Wang Y et al (2016) Enzyme-catalyzed formation of supramolecular hydrogels as promising vaccine adjuvants. Adv Funct Mater 26:1822–1829CrossRefGoogle Scholar
  35. 35.
    Yewdell JW (2010) Designing CD8+ T cell vaccines: it’s not rocket science. Curr Opin Immunol 22:402–410CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Raeburn J, Cardoso AZ, Adams DJ (2013) The importance of the self-assembly process to control mechanical properties of low molecular weight hydrogels. Chem Soc Rev 42:5143–5156CrossRefPubMedGoogle Scholar
  37. 37.
    Luo Z, Wu Q, Yang C et al (2017) A powerful CD8+ T-cell stimulating D-tetra-peptide hydrogel as a very promising vaccine adjuvant. Adv Mater 29:1601776CrossRefGoogle Scholar
  38. 38.
    Macher BA, Galili U (2008) The Galα1, 3Galβ1, 4GlcNAc-R (α-Gal) epitope: a carbohydrate of unique evolution and clinical relevance. Biochim Biophys Acta 1780:75–88CrossRefPubMedGoogle Scholar
  39. 39.
    Zhao F, Heesters BA, Chiu I et al (2014) L-Rhamnose-containing supramolecular nanofibrils as potential immunosuppressive materials. Org Biomol Chem 12:6816–6819CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Johansen P, Storni T, Rettig L et al (2008) Antigen kinetics determines immune reactivity. Proc Natl Acad Sci USA 105:5189–5194CrossRefPubMedGoogle Scholar
  41. 41.
    Boekhoven J, Hendriksen WE, Koper GJ et al (2015) Transient assembly of active materials fueled by a chemical reaction. Science 349:1075–1079CrossRefPubMedGoogle Scholar
  42. 42.
    Wang J, Liu K, Xing R et al (2016) Peptide self-assembly: thermodynamics and kinetics. Chem Soc Rev 45:5589–5604CrossRefPubMedGoogle Scholar
  43. 43.
    Tantakitti F, Boekhoven J, Wang X et al (2016) Energy landscapes and functions of supramolecular systems. Nat Mater 15:469–476CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Hirst AR, Roy S, Arora M et al (2010) Biocatalytic induction of supramolecular order. Nat Chem 2:1089–1094CrossRefPubMedGoogle Scholar
  45. 45.
    Guy B (2007) The perfect mix: recent progress in adjuvant research. Nat Rev Microbiol 5:505–517PubMedGoogle Scholar

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© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  1. 1.State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, and Collaborative Innovation Center of Chemical Science and Engineering (Tianjin)Nankai UniversityTianjinChina

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