Engineering synthetic vaccines using cues from natural immunity

Nature Materials

Volumn 12, Issue 11, 2013, Pages 978-990

  Irvine, Darrell J ^a,b,c   Swartz, Melody A ^d   Szeto, Gregory L ^a,b  

^a Massachusetts Institute of Technology Cambridge   (United States)

^b MASSACHUSETTS INSTITUTE OF TECHNOLOGY   (United States)

^c HOWARD HUGHES MEDICAL INSTITUTE   (United States)

^d EPFL   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

CELLS; CYTOLOGY; ENZYME ACTIVITY; IMMUNE SYSTEM; T-CELLS; TISSUE;

AUTOANTIBODIES; IMMUNE RESPONSE; IMMUNOMODULATORY; INTRACELLULAR COMPARTMENTS; SELF-TISSUES; SYNTHETIC MATERIALS; SYNTHETIC VACCINES; TARGET ORGANS;

VACCINES;

DRUG CARRIER; RECOMBINANT VACCINE;

ANIMAL; CHEMISTRY; ENGINEERING; HUMAN; IMMUNITY; IMMUNOLOGY; REVIEW;

ANIMALS; DRUG CARRIERS; ENGINEERING; HUMANS; IMMUNITY; VACCINES, SYNTHETIC;

EID: 84886287251     PISSN: 14761122     EISSN: 14764660     Source Type: Journal    
DOI: 10.1038/nmat3775     Document Type: Review

References (131)

1. Germain, R. N. Vaccines and the future of human immunology. Immunity 33, 441-450 (2010).
2. Pulendran, B., Li, S. & Nakaya, H. I. Systems vaccinology. Immunity 33, 516-529 (2010).
3. Plotkin, S. A. Vaccines: Past, present and future. Nature Med. 11, S5-S11 (2005).
4. Rappuoli, R. & Aderem, A. A 2020 vision for vaccines against HIV, tuberculosis and malaria. Nature 473, 463-469 (2011).
5. Mellman, I., Coukos, G. & Dranoff, G. Cancer immunotherapy comes of age. Nature 480, 480-489 (2011).
6. Topalian, S. L. et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. New Engl. J. Med. 366, 2443-2454 (2012).
7. Brahmer, J. R. et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. New Engl. J. Med. 366, 2455-2465 (2012).
8. Valenta, R. et al. From allergen genes to allergy vaccines. Annu. Rev. Immunol. 28, 211-241 (2010).
9. Dolgin, E. The inverse of immunity. Nature Med. 16, 740-743 (2010).
10. D'Argenio, D. A. & Wilson, C. B. A decade of vaccines: Integrating immunology and vaccinology for rational vaccine design. Immunity 33, 437-440 (2010).
11. Steinman, R. M. & Banchereau, J. Taking dendritic cells into medicine. Nature 449, 419-426 (2007).
12. Banchereau, J. & Steinman, R. M. Dendritic cells and the control of immunity. Nature 392, 245-252 (1998).
13. Kawai, T. & Akira, S. The roles of TLRs, RLRs and NLRs in pathogen recognition. Int. Immunol. 21, 317-337 (2009).
14. Bachmann, M. F. et al. The influence of antigen organization on B cell responsiveness. Science 262, 1448-1451 (1993).
15. Blander, J. M. & Medzhitov, R. Toll-dependent selection of microbial antigens for presentation by dendritic cells. Nature 440, 808-812 (2006).
16. Kovacsovics-Bankowski, M. & Rock, K. L. A phagosome-to-cytosol pathway for exogenous antigens presented on MHC class I molecules. Science 267, 243-246 (1995).
17. Lund, A. W. et al. VEGF-C promotes immune tolerance in B16 melanomas and cross-presentation of tumor antigen by lymph node lymphatics. Cell Rep. 1, 191-199 (2012).
18. Lin, M. L., Zhan, Y., Villadangos, J. A. & Lew, A. M. The cell biology of cross-presentation and the role of dendritic cell subsets. Immunol. Cell Biol. 86, 353-362 (2008).
19. Den Haan, J. M. & Bevan, M. J. Constitutive versus activation-dependent cross-presentation of immune complexes by CD8(+) and CD8(-) dendritic cells in vivo. J. Exp. Med. 196, 817-827 (2002).
20. Segura, E., Durand, M. & Amigorena, S. Similar antigen cross-presentation capacity and phagocytic functions in all freshly isolated human lymphoid organ-resident dendritic cells. J. Exp. Med. 210, 1035-1047 (2013).
21. Foged, C., Hansen, J. & Agger, E. M. License to kill: Formulation requirements for optimal priming of CD8(+) CTL responses with particulate vaccine delivery systems. Eur. J. Pharm. Sci. 45, 482-491 (2012).
22. Bachmann, M. F. & Jennings, G. T. Vaccine delivery: a matter of size, geometry, kinetics and molecular patterns. Nature Rev. Immunol. 10, 787-796 (2010).
23. Kourtis, I. C. et al. Peripherally administered nanoparticles target monocytic myeloid cells, secondary lymphoid organs and tumors in mice. PLoS One 8, e61646 (2013).
24. Swartz, M. A., Hirosue, S. & Hubbell, J. A. Engineering approaches to immunotherapy. Sci. Transl. Med. 4, 148rv149 (2012).
25. Villa, C. H. et al. Single-walled carbon nanotubes deliver peptide antigen into dendritic cells and enhance IgG responses to tumor-associated antigens. ACS Nano 5, 5300-5311 (2011).
26. Nembrini, C. et al. Nanoparticle conjugation of antigen enhances cytotoxic T-cell responses in pulmonary vaccination. Proc. Natl Acad. Sci. USA 108, E989-E997 (2011).
27. Reddy, S. et al. Exploiting lymphatic transport and complement activation in nanoparticle vaccines. Nature Biotechnol. 25, 1159-1164 (2007).
28. Fifis, T. et al. Size-dependent immunogenicity: therapeutic and protective properties of nano-vaccines against tumors. J. Immunol. 173, 3148-3154 (2004).
29. De Rose, R. et al. Binding, internalization, and antigen presentation of vaccine-loaded nanoengineered capsules in blood. Adv. Mater. 20, 4698-4703 (2008).
30. De Geest, B. G. et al. Surface-engineered polyelectrolyte multilayer capsules: synthetic vaccines mimicking microbial structure and function. Angew. Chem. Int. Ed. 51, 3862-3866 (2012).
31. Dierendonck, M. et al. Facile two-step synthesis of porous antigenloaded degradable polyelectrolyte microspheres. Angew. Chem. Int. Ed. 49, 8620-8624 (2010).
32. Perry, J. L., Herlihy, K. P., Napier, M. E. & DeSimone, J. M. PRINT: A novel platform toward shape and size specific nanoparticle theranostics. Acc. Chem. Res. 44, 990-998 (2011).
33. Galloway, A. L. et al. Development of a nanoparticle-based influenza vaccine using the PRINT technology. Nanomed Nanotechnol. Biol. Med. 9, 523-531 (2013).
34. Reis e Sousa, C. & Germain, R. N. Major histocompatibility complex class I presentation of peptides derived from soluble exogenous antigen by a subset of cells engaged in phagocytosis. J. Exp. Med. 182, 841-851 (1995).
35. Scott, E. A. et al. Dendritic cell activation and T cell priming with adjuvant- and antigen-loaded oxidation-sensitive polymersomes. Biomaterials 33, 6211-6219 (2012).
36. Hirosue, S., Kourtis, I. C., van der Vlies, A. J., Hubbell, J. A. & Swartz, M. A. Antigen delivery to dendritic cells by poly(propylene sulfide) nanoparticles with disulfide conjugated peptides: Cross-presentation and T cell activation. Vaccine 28, 7897-7906 (2010).
37. Moon, J. J. et al. Interbilayer-crosslinked multilamellar vesicles as synthetic vaccines for potent humoral and cellular immune responses. Nature Mater. 10, 243-251 (2011).
38. Nordly, P. et al. Immunity by formulation design: induction of high CD8+ T-cell responses by poly(I:C) incorporated into the CAF01 adjuvant via a double emulsion method. J. Control. Release 150, 307-317 (2011).
39. Zaks, K. et al. Efficient immunization and cross-priming by vaccine adjuvants containing TLR3 or TLR9 agonists complexed to cationic liposomes. J. Immunol. 176, 7335-7345 (2006).
40. Powell, T. J. et al. Plasmodium falciparum synthetic LbL microparticle vaccine elicits protective neutralizing antibody and parasite-specific cellular immune responses. Vaccine 31, 1898-1904 (2013).
41. Kasturi, S. P. et al. Programming the magnitude and persistence of antibody responses with innate immunity. Nature 470, 543-547 (2011).
42. Kazzaz, J. et al. Encapsulation of the immune potentiators MPL and RC529 in PLG microparticles enhances their potency. J. Control. Release 110, 566-573 (2006).
43. Zhu, Q. et al. Using 3 TLR ligands as a combination adjuvant induces qualitative changes in T cell responses needed for antiviral protection in mice. J. Clin. Investig. 120, 607-616 (2010).
44. Garaude, J., Kent, A., van Rooijen, N. & Blander, J. M. Simultaneous targeting of toll- and nod-like receptors induces effective tumor-specific immune responses. Sci. Transl. Med. 4, 120ra116 (2012).
45. Tacken, P. J. et al. Targeted delivery of TLR ligands to human and mouse dendritic cells strongly enhances adjuvanticity. Blood 118, 6836-6844 (2011).
46. Moon, J. J. et al. Enhancing humoral responses to a malaria antigen with nanoparticle vaccines that expand Tf?h cells and promote germinal center induction. Proc. Natl Acad. Sci. USA 109, 1080-1085 (2012).
47. Nguyen, D. N. et al. Lipid-derived nanoparticles for immunostimulatory RNA adjuvant delivery. Proc. Natl Acad. Sci. USA 109, E797-E803 (2012).
48. Ng, G. et al. Receptor-independent, direct membrane binding leads to cell-surface lipid sorting and Syk kinase activation in dendritic cells. Immunity 29, 807-818 (2008).
49. Flach, T. L. et al. Alum interaction with dendritic cell membrane lipids is essential for its adjuvanticity. Nature Med. 17, 479-487 (2011).
50. Marichal, T. et al. DNA released from dying host cells mediates aluminum adjuvant activity. Nature Med. 17, 996-1002 (2011).
51. Harris, J., Sharp, F. A. & Lavelle, E. C. The role of inflammasomes in the immunostimulatory effects of particulate vaccine adjuvants. Eur. J. Immunol. 40, 634-638 (2010).
52. Hornung, V. et al. Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization. Nature Immunol. 9, 847-856 (2008).
53. Shi, Y., Evans, J. E. & Rock, K. L. Molecular identification of a danger signal that alerts the immune system to dying cells. Nature 425, 516-521 (2003).
54. Ballester, M. et al. Nanoparticle conjugation and pulmonary delivery enhance the protective efficacy of Ag85B and CpG against tuberculosis. Vaccine 29, 6959-6966 (2011).
55. Sharp, F. A. et al. Uptake of particulate vaccine adjuvants by dendritic cells activates the NALP3 inflammasome. Proc. Natl Acad. Sci. USA 106, 870-875 (2009).
56. Demento, S. L. et al. Inflammasome-activating nanoparticles as modular systems for optimizing vaccine efficacy. Vaccine 27, 3013-3021 (2009).
57. De Geest, B. G. et al. Polymeric multilayer capsule-mediated vaccination induces protective immunity against cancer and viral infection. ACS Nano 6, 2136-2149 (2012).
58. Li, H., Li, Y., Jiao, J. & Hu, H. M. Alpha-alumina nanoparticles induce efficient autophagy-dependent cross-presentation and potent antitumour response. Nature Nanotech. 6, 645-650 (2011).
59. Thomas, S. N. et al. Engineering complement activation on polypropylene sulfide vaccine nanoparticles. Biomaterials 32, 2194-2203 (2011).
60. Moyano, D. F. et al. Nanoparticle hydrophobicity dictates immune response. J. Am. Chem. Soc. 134, 3965-3967 (2012).
61. Petersen, L. K. et al. Activation of innate immune responses in a pathogenmimicking manner by amphiphilic polyanhydride nanoparticle adjuvants. Biomaterials 32, 6815-6822 (2011).
62. Seong, S. Y. & Matzinger, P. Hydrophobicity: an ancient damageassociated molecular pattern that initiates innate immune responses. Nature Rev. Immunol. 4, 469-478 (2004).
63. Rudra, J. S., Tian, Y. F., Jung, J. P. & Collier, J. H. A self-assembling peptide acting as an immune adjuvant. Proc. Natl Acad. Sci. USA 107, 622-627 (2010).
64. Getts, D. R. et al. Microparticles bearing encephalitogenic peptides induce T-cell tolerance and ameliorate experimental autoimmune encephalomyelitis. Nature Biotechnol. 30, 1217-1224 (2012).
65. Lewis, J. S., Zaveri, T. D., Crooks, C. P. II & Keselowsky, B. G. Microparticle surface modifications targeting dendritic cells for non-activating applications. Biomaterials 33, 7221-7232 (2012).
66. Yeste, A., Nadeau, M., Burns, E. J., Weiner, H. L. & Quintana, F. J. Nanoparticle-mediated codelivery of myelin antigen and a tolerogenic small molecule suppresses experimental autoimmune encephalomyelitis. Proc. Natl Acad. Sci. USA 109, 11270-11275 (2012).
67. Tsai, S. et al. Reversal of autoimmunity by boosting memory-like autoregulatory T cells. Immunity 32, 568-580 (2010).
68. Wherry, E. J., Blattman, J. N., Murali-Krishna, K., van der Most, R. & Ahmed, R. Viral persistence alters CD8 T-cell immunodominance and tissue distribution and results in distinct stages of functional impairment. J. Virol. 77, 4911-4927 (2003).
69. Mueller, S. N. & Ahmed, R. High antigen levels are the cause of T cell exhaustion during chronic viral infection. Proc. Natl Acad. Sci. USA 106, 8623-8628 (2009).
70. Pape, K. A., Catron, D. M., Itano, A. A. & Jenkins, M. K. The humoral immune response is initiated in lymph nodes by B cells that acquire soluble antigen directly in the follicles. Immunity 26, 491-502 (2007).
71. Itano, A. A. et al. Distinct dendritic cell populations sequentially present antigen to CD4 T cells and stimulate different aspects of cell-mediated immunity. Immunity 19, 47-57 (2003).
72. Johansen, P. et al. Antigen kinetics determines immune reactivity. Proc. Natl Acad. Sci. USA 105, 5189-5194 (2008).
73. Howland, S. W. & Wittrup, K. D. Antigen release kinetics in the phagosome are critical to cross-presentation efficiency. J. Immunol. 180, 1576-1583 (2008).
74. Marx, P. A. et al. Protection against vaginal SIV transmission with microencapsulated vaccine. Science 260, 1323-1327 (1993).
75. Neutra, M. R. & Kozlowski, P. A. Mucosal vaccines: the promise and the challenge. Nature Rev. Immunol. 6, 148-158 (2006).
76. Zhu, G., Mallery, S. & Schwendeman, S. Stabilization of proteins encapsulated in injectable poly (lactide-co-glycolide). Nature Biotechnol. 18, 52-57 (2000).
77. Zhu, Q. et al. Large intestine-targeted, nanoparticle-releasing oral vaccine to control genitorectal viral infection. Nature Med. 18, 1291-1296 (2012).
78. Fujkuyama, Y. et al. Novel vaccine development strategies for inducing mucosal immunity. Expert Rev. Vaccines 11, 367-379 (2012).
79. Sullivan, S. P. et al. Dissolving polymer microneedle patches for influenza vaccination. Nature Med. 16, 915-920 (2010).
80. Zaric, M. et al. Skin dendritic cell targeting via microneedle arrays laden with antigen-encapsulated poly-d, l-lactide-co-glycolide nanoparticles induces efficient antitumor and antiviral immune responses. ACS Nano 7, 2042-2055 (2013).
81. Prow, T. W. et al. Nanopatch-targeted skin vaccination against West Nile Virus and Chikungunya virus in mice. Small 6, 1776-1784 (2010).
82. DeMuth, P. C. et al. Polymer multilayer tattooing for enhanced DNA vaccination. Nature Mater. 12, 367-376 (2013).
83. Atuma, C., Strugala, V., Allen, A. & Holm, L. The adherent gastrointestinal mucus gel layer: thickness and physical state in vivo. Am. J. Physiol. Gastrointest. Liver Physiol. 280, G922-G929 (2001).
84. Lai, S. K., Wang, Y. Y., Hida, K., Cone, R. & Hanes, J. Nanoparticles reveal that human cervicovaginal mucus is riddled with pores larger than viruses. Proc. Natl Acad. Sci. USA 107, 598-603 (2010).
85. Tang, B. C. et al. Biodegradable polymer nanoparticles that rapidly penetrate the human mucus barrier. Proc. Natl Acad. Sci. USA 106, 19268-19273 (2009).
86. Lai, S. K. et al. Rapid transport of large polymeric nanoparticles in fresh undiluted human mucus. Proc. Natl Acad. Sci. USA 104, 1482-1487 (2007).
87. Cu, Y., Booth, C. J. & Saltzman, W. M. In vivo distribution of surfacemodified PLGA nanoparticles following intravaginal delivery. J. Control. Release 156, 258-264 (2011).
88. Ensign, L. M. et al. Mucus-penetrating nanoparticles for vaginal drug delivery protect against herpes simplex virus. Sci. Transl. Med. 4, 138ra179 (2012).
89. Nochi, T. et al. Nanogel antigenic protein-delivery system for adjuvant-free intranasal vaccines. Nature Mater. 9, 572-578 (2010).
90. Fleury, M. E., Boardman, K. C. & Swartz, M. A. Autologous morphogen gradients by subtle interstitial flow and matrix interactions. Biophys. J. 91, 113-121 (2006).
91. Tang, L., Fan, T. M., Borst, L. B. & Cheng, J. Synthesis and biological response of size-specific, monodisperse drug-silica nanoconjugates. ACS Nano 6, 3954-3966 (2012).
92. Bershteyn, A. et al. Robust IgG responses to nanograms of antigen using a biomimetic lipid-coated particle vaccine. J. Control. Release 157, 354-365 (2012).
93. Murthy, N. et al. A macromolecular delivery vehicle for protein-based vaccines: acid-degradable protein-loaded microgels. Proc. Natl Acad. Sci. USA 100, 4995-5000 (2003).
94. Hu, Y. et al. Cytosolic delivery of membrane-impermeable molecules in dendritic cells using pH-responsive core-shell nanoparticles. Nano Lett. 7, 3056-3064 (2007).
95. Su, X., Fricke, J., Kavanagh, D. G. & Irvine, D. J. In vitro and in vivo mRNA delivery using lipid-enveloped pH-responsive polymer nanoparticles. Mol. Pharm. 8, 774-787 (2011).
96. Haining, W. N. et al. pH-triggered microparticles for peptide vaccination. J. Immunol. 173, 2578-2585 (2004).
97. Heffernan, M. J., Kasturi, S. P., Yang, S. C., Pulendran, B. & Murthy, N. The stimulation of CD8+ T cells by dendritic cells pulsed with polyketal microparticles containing ion-paired protein antigen and poly(inosinic acid)- poly(cytidylic acid). Biomaterials 30, 910-918 (2009).
98. Vasdekis, A. E., Scott, E. A., O'Neil, C. P., Psaltis, D. & Hubbell, J. A. Precision intracellular delivery based on optofluidic polymersome rupture. ACS Nano 6, 7850-7857 (2012).
99. Shen, H. et al. Enhanced and prolonged cross-presentation following endosomal escape of exogenous antigens encapsulated in biodegradable nanoparticles. Immunology 117, 78-88 (2006).
100. Geall, A. J. et al. Nonviral delivery of self-amplifying RNA vaccines. Proc. Natl Acad. Sci. USA 109, 14604-14609 (2012).
101. Verma, A. et al. Surface-structure-regulated cell-membrane penetration by monolayer-protected nanoparticles. Nature Mater. 7, 588-595 (2008).
102. Marrack, P., McKee, A. & Munks, M. Towards an understanding of the adjuvant action of aluminium. Nature Rev. Immunol. 9, 287-293 (2009).
103. Hutchison, S. et al. Antigen depot is not required for alum adjuvanticity. FASEB J. 26, 1272-1279 (2012).
104. Gupta, R. K., Chang, A. C., Griffin, P., Rivera, R. & Siber, G. R. In vivo distribution of radioactivity in mice after injection of biodegradable polymer microspheres containing 14C-labeled tetanus toxoid. Vaccine 14, 1412-1416 (1996).
105. Preis, I. & Langer, R. S. A single-step immunization by sustained antigen release. J. Immunol. Methods 28, 193-197 (1979).
106. Thomasin, C., Corradin, G., Men, Y., Merkle, H. P. & Gander, B. Tetanus toxoid and synthetic malaria antigen containing poly(lactide)/ poly(lactideco- glycolide) microspheres: Importance of polymer degradation and antigen release for immune response. J. Control. Release 41, 131-145 (1996).
107. Hailemichael, Y. et al. Persistent antigen at vaccination sites induces tumorspecific CD8+ T cell sequestration, dysfunction and deletion. Nature Med. 19, 465-472 (2013).
108. Jewell, C. M., Lopez, S. C. & Irvine, D. J. In situ engineering of the lymph node microenvironment via intranodal injection of adjuvant-releasing polymer particles. Proc. Natl Acad. Sci. USA 108, 15745-15750 (2011).
109. St John, A. L., Chan, C. Y., Staats, H. F., Leong, K. W. & Abraham, S. N. Synthetic mast-cell granules as adjuvants to promote and polarize immunity in lymph nodes. Nature Mater. 11, 250-257 (2012).
110. Braumuller, H. et al. T-helper-1-cell cytokines drive cancer into senescence. Nature 494, 361-365 (2013).
111. Reiner, S. L. & Locksley, R. M. The regulation of immunity to Leishmania major. Annu. Rev. Immunol. 13, 151-177 (1995).
112. Ali, O. A., Emerich, D., Dranoff, G. & Mooney, D. J. In situ regulation of DC subsets and T cells mediates tumor regression in mice. Sci. Transl. Med. 1, 8ra19 (2009).
113. Ali, O. A., Huebsch, N., Cao, L., Dranoff, G. & Mooney, D. J. Infectionmimicking materials to program dendritic cells in situ. Nature Mater. 8, 151-158 (2009).
114. Singh, A. et al. An injectable synthetic immune-priming center mediates efficient T-cell class switching and T-helper 1 response against B cell lymphoma. J. Control. Release 155, 184-192 (2011).
115. Langhorne, J. et al. The relevance of non-human primate and rodent malaria models for humans. Malaria J. 10, 23 (2011).
116. Morgan, C. et al. The use of nonhuman primate models in HIV vaccine development. PLoS Med. 5, e173 (2008).
117. Tsuji, K. et al. Induction of immune response against NY-ESO-1 by CHP-NY-ESO-1 vaccination and immune regulation in a melanoma patient. Cancer Immunol. Immunother. CII 57, 1429-1437 (2008).
118. Ataman-Onal, Y. et al. Surfactant-free anionic PLA nanoparticles coated with HIV-1 p24 protein induced enhanced cellular and humoral immune responses in various animal models. J. Control. Release 112, 175-185 (2006).
119. Otten, G. et al. Induction of broad and potent anti-human immunodeficiency virus immune responses in rhesus macaques by priming with a DNA vaccine and boosting with protein-adsorbed polylactide coglycolide microparticles. J. Virol. 77, 6087-6092 (2003).
120. Appay, V., Douek, D. C. & Price, D. A. CD8+ T cell efficacy in vaccination and disease. Nature Med. 14, 623-628 (2008).
121. Nimmerjahn, F. & Ravetch, J. V. Antibody-mediated modulation of immune responses. Immunol. Rev. 236, 265-275 (2010).
122. Virgin, H. W. & Walker, B. D. Immunology and the elusive AIDS vaccine. Nature 464, 224-231 (2010).
123. Crow, J. M. HPV: The global burden. Nature 488, S2-S3 (2012).
124. Ma, B., Xu, Y., Hung, C-F. & Wu, T-C. HPV and therapeutic vaccines: where are we in 2010? Curr. Cancer Ther. Rev. 6, 81-103 (2010).
125. Klebanoff, C. A., Acquavella, N., Yu, Z. & Restifo, N. P. Therapeutic cancer vaccines: are we there yet? Immunol. Rev. 239, 27-44 (2011).
126. Harrison, L. C. Vaccination against self to prevent autoimmune disease: the type 1 diabetes model. Immunol. Cell Biol. 86, 139-145 (2008).
127. Wisniewski, T. & Goni, F. Immunomodulation for prion and prion-related diseases. Expert Rev. Vaccines 9, 1441-1452 (2010).
128. Linhart, B. & Valenta, R. Vaccines for allergy. Curr. Opin. Immunol. 24, 354-360 (2012).
129. Sela, M. & Mozes, E. Therapeutic vaccines in autoimmunity. Proc. Natl Acad. Sci. USA 101, Suppl. 2, 14586-14592 (2004).
130. Velluto, D. et al. PEG-b-PPS-b-PEI micelles and PEG-b-PPS/ PEG-b-PPS-b-PEI mixed micelles as non-viral vectors for plasmid DNA: Tumor immunotoxicity in B16F10 melanoma. Biomaterials 32, 9839-9847 (2011).
131. Caruso, F. et al. Enzyme encapsulation in layer-by-layer engineered polymer multilayer capsules. Langmuir 16, 1485-1488 (2000).