Journal Home > Volume 11 , Issue 1
Nano Research 2018, 11(1): 370-382 https://doi.org/10.1007/s12274-017-1640-1
Research Article | Issue | Published: 04 August 2017

Pristine mesoporous carbon hollow spheres as safe adjuvants induce excellent Th2-biased immune response

Show Author's Information Manasi Jambhrunkar1,  Meihua Yu1,  Hongwei Zhang1,  Prasanna Abbaraju1,  Anand Kumar Meka1,  Antonino Cavallaro2,  Yao Lu1,  Neena Mitter2( ),  Chengzhong Yu1( )
Australian Institute for Bioengineering and NanotechnologyThe University of QueenslandBrisbaneQLD4072Australia
Queensland Alliance for Agriculture and Food InnovationThe University of QueenslandBrisbaneQLD4072Australia
Keywords:
invaginated mesoporous carbon hollow spheres, ovalbumin, vaccine, immune response
Cite this article:
Jambhrunkar M, Yu M, Zhang H, et al. Pristine mesoporous carbon hollow spheres as safe adjuvants induce excellent Th2-biased immune response. Nano Research, 2018, 11(1): 370-382. https://doi.org/10.1007/s12274-017-1640-1
Download citation
EndNote(RIS)
BibTeX

497

Views

12

Downloads

Citations

14

Crossref

N/A

WoS

15

Scopus

2

CSCD

Abstract Full text Electronic supplementary material About this article

The development of a safe and effective adjuvant that amplifies the immune response to an antigen is important for vaccine delivery. In this study, we developed pristine mesoporous carbon hollow spheres as high-capacity vaccine protein nanocarriers and safe adjuvants for boosting the immune response. Mono-dispersed invaginated mesostructured hollow carbon spheres (IMHCSs) have an average particle size of ~200 nm, large pore size of 15 nm, and high pore volume of 2.85 cm3·g-1. IMHCSs exhibited a very high loading capacity (1, 040 μg·mg-1) towards ovalbumin (OVA, a model antigen), controlled OVA release behavior, excellent safety profile to normal cells, and high antigen delivery efficacy towards macrophages. In vivo immunization studies in mice demonstrated that OVA-loaded IMHCSs induced a 3-fold higher IgG response compared to a traditional adjuvant QuilA used in veterinary vaccine research. OVA delivered by IMHCSs induced a higher IgG1 concentration than IgG2a, indicating a T-helper 2 (Th2)-polarized response. Interferon-γ and interleukin-4 concentration analysis revealed both T-helper 1 (Th1) and Th2 immune responses induced by OVA-loaded IMHCSs. IMHCSs are safer adjuvants than QuilA. Our study revealed that pure IMHCSs without further functionalization can be used as a safe adjuvant for promoting Th2-biased immune responses for vaccine delivery.


menu
Abstract
Full text
Outline
Electronic supplementary material
About this article

Pristine mesoporous carbon hollow spheres as safe adjuvants induce excellent Th2-biased immune response

Show Author's information Manasi Jambhrunkar1, Meihua Yu1, Hongwei Zhang1, Prasanna Abbaraju1, Anand Kumar Meka1, Antonino Cavallaro2, Yao Lu1, Neena Mitter2( ), Chengzhong Yu1( )
Australian Institute for Bioengineering and NanotechnologyThe University of QueenslandBrisbaneQLD4072Australia
Queensland Alliance for Agriculture and Food InnovationThe University of QueenslandBrisbaneQLD4072Australia

Abstract

The development of a safe and effective adjuvant that amplifies the immune response to an antigen is important for vaccine delivery. In this study, we developed pristine mesoporous carbon hollow spheres as high-capacity vaccine protein nanocarriers and safe adjuvants for boosting the immune response. Mono-dispersed invaginated mesostructured hollow carbon spheres (IMHCSs) have an average particle size of ~200 nm, large pore size of 15 nm, and high pore volume of 2.85 cm3·g-1. IMHCSs exhibited a very high loading capacity (1, 040 μg·mg-1) towards ovalbumin (OVA, a model antigen), controlled OVA release behavior, excellent safety profile to normal cells, and high antigen delivery efficacy towards macrophages. In vivo immunization studies in mice demonstrated that OVA-loaded IMHCSs induced a 3-fold higher IgG response compared to a traditional adjuvant QuilA used in veterinary vaccine research. OVA delivered by IMHCSs induced a higher IgG1 concentration than IgG2a, indicating a T-helper 2 (Th2)-polarized response. Interferon-γ and interleukin-4 concentration analysis revealed both T-helper 1 (Th1) and Th2 immune responses induced by OVA-loaded IMHCSs. IMHCSs are safer adjuvants than QuilA. Our study revealed that pure IMHCSs without further functionalization can be used as a safe adjuvant for promoting Th2-biased immune responses for vaccine delivery.

Keywords: invaginated mesoporous carbon hollow spheres, ovalbumin, vaccine, immune response

References(58)

1

Petrovsky, N.; Aguilar, J. C. Vaccine adjuvants: Current state and future trends. Immunol. Cell Biol. 2004, 82, 488-496.
DOI Google Scholar
2

Marrack, P.; McKee, A. S.; Munks, M. W. Towards an understanding of the adjuvant action of aluminium. Nat. Rev. Immunol. 2009, 9, 287-293.
DOI Google Scholar
3

Reed, S. G.; Orr, M. T.; Fox, C. B. Key roles of adjuvants in modern vaccines. Nat. Med. 2013, 19, 1597-1608.
DOI Google Scholar
4

Amanna, I. J.; Slifka, M. K. Contributions of humoral and cellular immunity to vaccine-induced protection in humans. Virology 2011, 411, 206-215.
DOI Google Scholar
5

Romagnani, S. The Th1/Th2 paradigm. Immunol. Today 1997, 18, 263-266.
DOI Google Scholar
6
Vogel, F. R.; Powell, M. F. A compendium of vaccine adjuvants and excipients. In Vaccine Design: The Subunit and Adjuvant Approach. Powell, M. F.; Newman, M. J., Eds.; Springer: US, 1995; pp 141-228.https://doi.org/10.1007/978-1-4615-1823-5_7
DOI
7

Singh, M.; O'Hagan, D. Advances in vaccine adjuvants. Nat. Biotechnol. 1999, 17, 1075-1081.
DOI Google Scholar
8

Relyveld, E. H.; Bizzini, B.; Gupta, R. K. Rational approaches to reduce adverse reactions in man to vaccines containing tetanus and diphtheria toxoids. Vaccine 1998, 16, 1016-1023.
DOI Google Scholar
9

Gupta, R. K. Aluminum compounds as vaccine adjuvants. Adv. Drug Deliv. Rev. 1998, 32, 155-172.
DOI Google Scholar
10

Freund, J.; Casals, J.; Hosmer, E. P. Sensitization and antibody formation after injection of tubercle bacilli and paraffin oil. Proc. Soc. Exp. Biol. Med. 1937, 37, 509-513.
DOI Google Scholar
11

Zhao, L.; Seth, A.; Wibowo, N.; Zhao, C. X.; Mitter, N.; Yu, C. Z.; Middelberg, A. P. J. Nanoparticle vaccines. Vaccine 2014, 32, 327-337.
DOI Google Scholar
12

Smith, D. M.; Simon, J. K.; Baker, J. R., Jr. Applications of nanotechnology for immunology. Nat. Rev. Immunol. 2013, 13, 592-605.
DOI Google Scholar
13

Oyewumi, M. O.; Kumar, A.; Cui, Z. R. Nano-microparticles as immune adjuvants: Correlating particle sizes and the resultant immune responses. Expert Rev. Vaccines 2010, 9, 1095-1107.
DOI Google Scholar
14

Gregory, A. E.; Titball, R.; Williamson, D. Vaccine delivery using nanoparticles. Front. Cell. Infect. Microbiol. 2013, 3, 13.
DOI Google Scholar
15

Zhang, W. F.; Wang, L. Y.; Liu, Y.; Chen, X. M.; Liu, Q.; Jia, J. L.; Yang, T. Y.; Qiu, S. H.; Ma, G. H. Immune responses to vaccines involving a combined antigen-nanoparticle mixture and nanoparticle-encapsulated antigen formulation. Biomaterials 2014, 35, 6086-6097.
DOI Google Scholar
16

Mahony, D.; Cavallaro, A. S.; Stahr, F.; Mahony, T. J.; Qiao, S. Z.; Mitter, N. Mesoporous silica nanoparticles act as a self-adjuvant for ovalbumin model antigen in mice. Small 2013, 9, 3138-3146.
DOI Google Scholar
17

Yan, S. Y.; Rolfe, B. E.; Zhang, B.; Mohammed, Y. H.; Gu, W. Y.; Xu, Z. P. Polarized immune responses modulated by layered double hydroxides nanoparticle conjugated with CpG. Biomaterials 2014, 35, 9508-9516.
DOI Google Scholar
18

Wang, T. Y.; Zou, M. J.; Jiang, H. T.; Ji, Z. S.; Gao, P.; Cheng, G. Synthesis of a novel kind of carbon nanoparticle with large mesopores and macropores and its application as an oral vaccine adjuvant. Eur. J. Pharm. Sci. 2011, 44, 653-659.
DOI Google Scholar
19

Giddam, A. K.; Zaman, M.; Skwarczynski, M.; Toth, I. Liposome-based delivery system for vaccine candidates: Constructing an effective formulation. Nanomedicine 2012, 7, 1877-1893.
DOI Google Scholar
20

Vasiliev, Y. M. Chitosan-based vaccine adjuvants: Incomplete characterization complicates preclinical and clinical evaluation. Expert Rev. Vaccines 2015, 14, 37-53.
DOI Google Scholar
21

Tobío, M.; Nolley, J.; Guo, Y. Y.; McIver, J.; Alonso, M. J. A novel system based on a poloxamer/PLGA blend as a tetanus toxoid delivery vehicle. Pharm. Res. 1999, 16, 682-688.
DOI Google Scholar
22
Dobrovolskaia, M. A.; McNeil, S. E. Immunological properties of engineered nanomaterials: An introduction. In Handbook of Immunological Properties of Engineered Nanomaterials. Dobrovolskaia, M. A.; McNeil, S. E., Eds.; World Scientific Publishing Co. Pte. Ltd. : Singapore, 2013; pp 1-23.https://doi.org/10.1142/8390
DOI
23

Moyano, D. F.; Goldsmith, M.; Solfiell, D. J.; Landesman- Milo, D.; Miranda, O. R.; Peer, D.; Rotello, V. M. Nanoparticle hydrophobicity dictates immune response. J. Am. Chem. Soc. 2012, 134, 3965-3967.
DOI Google Scholar
24

Kobayashi, K.; Wei, J. J.; Iida, R.; Ijiro, K.; Niikura, K. Surface engineering of nanoparticles for therapeutic applications. Polym. J. 2014, 46, 460-468.
DOI Google Scholar
25

Bianco, A.; Kostarelos, K.; Partidos, C. D.; Prato, M. Biomedical applications of functionalised carbon nanotubes. Chem. Commun. 2005, 571-577.
DOI Google Scholar
26

Liu, Z.; Tabakman, S.; Welsher, K.; Dai, H. J. Carbon nanotubes in biology and medicine: In vitro and in vivo detection, imaging and drug delivery. Nano. Res. 2009, 2, 85-120.
DOI Google Scholar
27

Parra, J.; Abad-Somovilla, A.; Mercader, J. V.; Taton, T. A.; Abad-Fuentes, A. Carbon nanotube-protein carriers enhance size-dependent self-adjuvant antibody response to haptens. J. Control. Release 2013, 170, 242-251.
DOI Google Scholar
28

Pantarotto, D.; Partidos, C. D.; Graff, R.; Hoebeke, J.; Briand, J. P.; Prato, M.; Bianco, A. Synthesis, structural characterization, and immunological properties of carbon nanotubes functionalized with peptides. J. Am. Chem. Soc. 2003, 125, 6160-6164.
DOI Google Scholar
29

Kim, T. -W.; Chung, P. -W.; Slowing, I. I.; Tsunoda, M.; Yeung, E. S.; Lin, V. S. Y. Structurally ordered mesoporous carbon nanoparticles as transmembrane delivery vehicle in human cancer cells. Nano Lett. 2008, 8, 3724-3727.
DOI Google Scholar
30

Wang, J.; Hu, Z. B.; Xu, J. X.; Zhao, Y. L. Therapeutic applications of low-toxicity spherical nanocarbon materials. NPG Asia Mater. 2014, 6, e84.
DOI Google Scholar
31

Zhang, H. W.; Yu, M. H.; Song, H.; Noonan, O.; Zhang, J.; Yang, Y. N.; Zhou, L.; Yu, C. Z. Self-organized mesostructured hollow carbon nanoparticles via a surfactant-free sequential heterogeneous nucleation pathway. Chem. Mater. 2015, 27, 6297-6304.
DOI Google Scholar
32

Liu, H. L.; Zhang, Y. L.; Yang, N.; Zhang, Y. X.; Liu, X. Q.; Li, C. G.; Zhao, Y.; Wang, Y. G.; Zhang, G. G.; Yang, P. et al. A functionalized single-walled carbon nanotube-induced autophagic cell death in human lung cells through Akt- TSC2-mTOR signaling. Cell Death Dis. 2011, 2, e159.
DOI Google Scholar
33

Fang, Y.; Gu, D.; Zou, Y.; Wu, Z. X.; Li, F. Y.; Che, R. C.; Deng, Y. H.; Tu, B.; Zhao, D. Y. A low-concentration hydrothermal synthesis of biocompatible ordered mesoporous carbon nanospheres with tunable and uniform size. Angew. Chem., Int. Ed. 2010, 49, 7987-7991.
DOI Google Scholar
34

Demento, S. L.; Cui, W. G.; Criscione, J. M.; Stern, E.; Tulipan, J.; Kaech, S. M.; Fahmy, T. M. Role of sustained antigen release from nanoparticle vaccines in shaping the T cell memory phenotype. Biomaterials 2012, 33, 4957-4964.
DOI Google Scholar
35

Wang, T. Y.; Jiang, H. T.; Zhao, Q. F.; Wang, S. L.; Zou, M. J.; Cheng, G. Enhanced mucosal and systemic immune responses obtained by porous silica nanoparticles used as an oral vaccine adjuvant: Effect of silica architecture on immunological properties. Int. J. Pharm. 2012, 436, 351-358.
DOI Google Scholar
36

Musumeci, T.; Ventura, C. A.; Giannone, I.; Ruozi, B.; Montenegro, L.; Pignatello, R.; Puglisi, G. PLA/PLGA nanoparticles for sustained release of docetaxel. Int. J. Pharm. 2006, 325, 172-179.
DOI Google Scholar
37

Du, J.; Wang, S. T.; You, H.; Zhao, X. S. Understanding the toxicity of carbon nanotubes in the environment is crucial to the control of nanomaterials in producing and processing and the assessment of health risk for human: A review. Environ. Toxicol. Pharmacol. 2013, 36, 451-462.
DOI Google Scholar
38

Gupta, R. K.; Relyveld, E. H.; Lindblad, E. B.; Bizzini, B.; Ben-Efraim, S.; Gupta, C. K. Adjuvants—A balance between toxicity and adjuvanticity. Vaccine 1993, 11, 293-306.
DOI Google Scholar
39

Wang, J.; Hu, Z. B.; Xu, J. X.; Zhao, Y. L. Therapeutic applications of low-toxicity spherical nanocarbon materials. NPG Asia Mater. 2014, 6, e84.
DOI Google Scholar
40

Fiorito, S.; Serafino, A.; Andreola, F.; Togna, A.; Togna, G. Toxicity and biocompatibility of carbon nanoparticles. J. Nanosci. Nanotechnol. 2006, 6, 591-599.
DOI Google Scholar
41

Wang, C.; Li, P.; Liu, L. L.; Pan, H.; Li, H. C.; Cai, L. T.; Ma, Y. F. Self-adjuvanted nanovaccine for cancer immunotherapy: Role of lysosomal rupture-induced ROS in MHC class Ⅰ antigen presentation. Biomaterials 2016, 79, 88-100.
DOI Google Scholar
42

Kalish, R. S. Antigen processing: The gateway to the immune response. J. Am. Acad. Dermatol. 1995, 32, 640-652.
DOI Google Scholar
43

Vyas, J. M.; Van der Veen, A. G.; Ploegh, H. L. The known unknowns of antigen processing and presentation. Nat. Rev. Immunol. 2008, 8, 607-618.
DOI Google Scholar
44

Mantegazza, A. R.; Magalhaes, J. G.; Amigorena, S.; Marks, M. S. Presentation of phagocytosed antigens by MHC class Ⅰ and Ⅱ. Traffic 2013, 14, 135-152.
DOI Google Scholar
45

Rafiq, K.; Bergtold, A.; Clynes, R. Immune complex-mediated antigen presentation induces tumor immunity. J. Clin. Invest. 2002, 110, 71-79.
DOI Google Scholar
46

Gu, L.; Ruff, L. E.; Qin, Z. T.; Corr, M.; Hedrick, S. M.; Sailor, M. J. Multivalent porous silicon nanoparticles enhance the immune activation potency of agonistic CD40 antibody. Adv. Mater. 2012, 24, 3981-3987.
DOI Google Scholar
47

Yuba, E. Design of pH-sensitive polymer-modified liposomes for antigen delivery and their application in cancer immunotherapy. Polym. J. 2016, 48, 761-771.
DOI Google Scholar
48

Seong, S. Y.; Matzinger, P. Hydrophobicity: An ancient damage-associated molecular pattern that initiates innate immune responses. Nat. Rev. Immunol. 2004, 4, 469-478.
DOI Google Scholar
49

Vogel, F. R. Improving vaccine performance with adjuvants. Clin. Infect. Dis. 2000, 30, S266-S270.
DOI Google Scholar
50

Elgueta, R.; Benson, M. J.; De Vries, V. C.; Wasiuk, A.; Guo, Y. X.; Noelle, R. J. Molecular mechanism and function of CD40/CD40L engagement in the immune system. Immunol. Rev. 2009, 229, 152-172.
DOI Google Scholar
51

Kaiko, G. E.; Horvat, J. C.; Beagley, K. W.; Hansbro, P. M. Immunological decision-making: How does the immune system decide to mount a helper T-cell response? Immunology 2008, 123, 326-338.
DOI Google Scholar
52

Vella, A. T.; Dow, S.; Potter, T. A.; Kappler, J.; Marrack, P. Cytokine-induced survival of activated T cells in vitro and in vivo. Proc. Natl. Acad. Sci. USA 1998, 95, 3810-3815.
DOI Google Scholar
53

Sun, B. B.; Ji, Z. X.; Liao, Y. P.; Wang, M. Y.; Wang, X.; Dong, J. Y.; Chang, C. H.; Li, R. B.; Zhang, H. Y.; Nel, A. E. et al. Engineering an effective immune adjuvant by designed control of shape and crystallinity of aluminum oxyhydroxide nanoparticles. ACS Nano 2013, 7, 10834-10849.
DOI Google Scholar
54

Fujimaki, H.; Ozawa, M.; Imai, T.; Kubota, K.; Watanabe, N. Adjuvant effects of aluminum silicate on IgE and IgG1 antibody production in mice. Int. Arch. Allergy Immunol. 1984, 75, 351-356.
DOI Google Scholar
55

Whitekus, M. J.; Li, N.; Zhang, M.; Wang, M. Y.; Horwitz, M. A.; Nelson, S. K.; Horwitz, L. D.; Brechun, N.; Diaz- Sanchez, D.; Nel, A. E. Thiol antioxidants inhibit the adjuvant effects of aerosolized diesel exhaust particles in a murine model for ovalbumin sensitization. J. Immunol. 2002, 168, 2560-2567.
DOI Google Scholar
56

Liu, Q.; Jia, J. L.; Yang, T. Y.; Fan, Q. Z.; Wang, L. Y.; Ma, G. H. Pathogen-mimicking polymeric nanoparticles based on dopamine polymerization as vaccines adjuvants induce robust humoral and cellular immune responses. Small 2016, 12, 1744-1757.
DOI Google Scholar
57

Kono, H.; Rock, K. L. How dying cells alert the immune system to danger. Nat. Rev. Immunol. 2008, 8, 279-289.
DOI Google Scholar
58

Chung, E. Y.; Kim, S. J.; Ma, X. J. Regulation of cytokine production during phagocytosis of apoptotic cells. Cell Res. 2006, 16, 154-161.
DOI Google Scholar
File
nr-11-1-370_ESM.pdf (1.4 MB)
Publication history
Copyright
Acknowledgements

Publication history

Received: 15 January 2017
Revised: 01 April 2017
Accepted: 08 April 2017
Published: 04 August 2017
Issue date: January 2018

Copyright

© Tsinghua University Press and Springer-Verlag GmbH Germany 2017

Acknowledgements

Acknowledgements

We thank the support from Australian Research Council, the Australian Microscopy & Microanalysis Research Facility at the Centre for Microscopy and Microanalysis, The University of Queensland, and the Queensland node of the Australian National Fabrication Facility (ANFF). We appreciate the help of Prof. Ian Fraser and Dr. Stacey Cole for the use of ELISPOT reader at Diamantina Institute and Translational Research Institute at The University of Queensland.

Return