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Open Access 01-12-2014 | Research article

GM-CSF-loaded chitosan hydrogel as an immunoadjuvant enhances antigen-specific immune responses with reduced toxicity

Authors: Kyung Hee Noh, Yeong Min Park, Hyuk Soon Kim, Tae Heung Kang, Kwon-Ho Song, Young-Ho Lee, Yeongseon Byeon, Hat Nim Jeon, In Duk Jung, Byung Cheol Shin, Kyung-Mi Lee, Seung-Yong Seong, Hee Dong Han, Tae Woo Kim

Published in: BMC Immunology | Issue 1/2014

Abstract

Background

The application of vaccine adjuvants has been vigorously studied for a diverse range of diseases in order to improve immune responses and reduce toxicity. However, most adjuvants have limited uses in clinical practice due to their toxicity.

Methods

Therefore, to reduce health risks associated with the use of such adjuvants, we developed an advanced non-toxic adjuvant utilizing biodegradable chitosan hydrogel (CH-HG) containing ovalbumin (OVA) and granulocyte-macrophage colony-stimulating factor (GM-CSF) as a local antigen delivery system.

Results

After subcutaneous injection into mice, OVA/GM-CSF-loaded CH-HG demonstrated improved safety and enhanced OVA-specific antibody production compared to oil-based adjuvants such as Complete Freund’s adjuvant (CFA) or Incomplete Freund’s adjuvant (IFA). Moreover, CH-HG system-mediated immune responses was characterized by increased number of OVA-specific CD4⁺ and CD8⁺ INF-γ⁺ T cells, leading to enhanced humoral and cellular immunity.

Conclusions

In this study, the improved safety and enhanced immune response characteristics of our novel adjuvant system suggest the possibility of the extended use of adjuvants in clinical practice with reduced apprehension about toxic side effects.

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Wilson-Welder JH, Torres MP, Kipper MJ, Mallapragada SK, Wannemuehler MJ, Narasimhan B: Vaccine adjuvants: current challenges and future approaches. J Pharm Sci. 2009, 98 (4): 1278-1316. 10.1002/jps.21523.PubMedCrossRef

Riese P, Schulze K, Ebensen T, Prochnow B, Guzman CA: Vaccine adjuvants: key tools for innovative vaccine design. Curr Top Med Chem. 2013, 13 (20): 2562-2580. 10.2174/15680266113136660183.PubMedCrossRef

Reed SG, Orr MT, Fox CB: Key roles of adjuvants in modern vaccines. Nat Med. 2013, 19 (12): 1597-1608. 10.1038/nm.3409.PubMedCrossRef

Chapel HM, August PJ: Report of nine cases of accidental injury to man with Freund's complete adjuvant. Clin Exp Immunol. 1976, 24 (3): 538-541.PubMedPubMedCentral

Bijker MS, van den Eeden SJ, Franken KL, Melief CJ, Offringa R, van der Burg SH: CD8+ CTL priming by exact peptide epitopes in incomplete Freund's adjuvant induces a vanishing CTL response, whereas long peptides induce sustained CTL reactivity. J Immunol. 2007, 179 (8): 5033-5040. 10.4049/jimmunol.179.8.5033.PubMedCrossRef

Stewart-Tull DE: Freund's complete and incomplete adjuvants, preparation, and quality control standards for experimental laboratory animals use. Methods Mol Biol. 2010, 626: 59-72. 10.1007/978-1-60761-585-9_5.PubMedCrossRef

Seo SH, Han HD, Noh KH, Kim TW, Son SW: Chitosan hydrogel containing GMCSF and a cancer drug exerts synergistic anti-tumor effects via the induction of CD8+ T cell-mediated anti-tumor immunity. Clin Exp Metastasis. 2009, 26 (3): 179-187. 10.1007/s10585-008-9228-5.PubMedCrossRef

Han HD, Mora EM, Roh JW, Nishimura M, Lee SJ, Stone RL, Bar-Eli M, Lopez-Berestein G, Sood AK: Chitosan hydrogel for localized gene silencing. Cancer Biol Ther. 2011, 11 (9): 839-845. 10.4161/cbt.11.9.15185.PubMedPubMedCentralCrossRef

Han HD, Nam DE, Seo DH, Kim TW, Shin BC: Preparation and biodegradation of thermosensitive chitosan hydrogel as a function of pH and temperature. Macromol Res. 2004, 12: 507-511. 10.1007/BF03218435.CrossRef

10.

Zhang C, Wang B, Wang M: GM-CSF and IL-2 as adjuvant enhance the immune effect of protein vaccine against foot-and-mouth disease.Virol J 2011, 8:7.,

11.

Ullenhag GJ, Frodin JE, Strigard K, Mellstedt H, Magnusson CG: Induction of IgG subclass responses in colorectal carcinoma patients vaccinated with recombinant carcinoembryonic antigen. Cancer Res. 2002, 62 (5): 1364-1369.PubMed

12.

Disis ML, Bernhard H, Shiota FM, Hand SL, Gralow JR, Huseby ES, Gillis S, Cheever MA: Granulocyte-macrophage colony-stimulating factor: an effective adjuvant for protein and peptide-based vaccines. Blood. 1996, 88 (1): 202-210.PubMed

13.

Morrissey PJ, Bressler L, Park LS, Alpert A, Gillis S: Granulocyte-macrophage colony-stimulating factor augments the primary antibody response by enhancing the function of antigen-presenting cells. J Immunol. 1987, 139 (4): 1113-1119.PubMed

14.

Sun X, Hodge LM, Jones HP, Tabor L, Simecka JW: Co-expression of granulocyte-macrophage colony-stimulating factor with antigen enhances humoral and tumor immunity after DNA vaccination. Vaccine. 2002, 20 (9-10): 1466-1474. 10.1016/S0264-410X(01)00476-5.PubMedCrossRef

15.

Toubaji A, Hill S, Terabe M, Qian J, Floyd T, Simpson RM, Berzofsky JA, Khleif SN: The combination of GM-CSF and IL-2 as local adjuvant shows synergy in enhancing peptide vaccines and provides long term tumor protection. Vaccine. 2007, 25 (31): 5882-5891. 10.1016/j.vaccine.2007.05.040.PubMedCrossRef

16.

Reid CD, Stackpoole A, Meager A, Tikerpae J: Interactions of tumor necrosis factor with granulocyte-macrophage colony-stimulating factor and other cytokines in the regulation of dendritic cell growth in vitro from early bipotent CD34+ progenitors in human bone marrow. J Immunol. 1992, 149 (8): 2681-2688.PubMed

17.

Golumbek PT, Azhari R, Jaffee EM, Levitsky HI, Lazenby A, Leong K, Pardoll DM: Controlled release, biodegradable cytokine depots: a new approach in cancer vaccine design. Cancer Res. 1993, 53 (24): 5841-5844.PubMed

18.

Igartua M, Hernandez RM, Esquisabel A, Gascon AR, Calvo MB, Pedraz JL: Enhanced immune response after subcutaneous and oral immunization with biodegradable PLGA microspheres. J Control Release. 1998, 56 (1-3): 63-73. 10.1016/S0168-3659(98)00077-7.PubMedCrossRef

19.

Chesson CB, Huelsmann EJ, Lacek AT, Kohlhapp FJ, Webb MF, Nabatiyan A, Zloza A, Rudra JS: Antigenic peptide nanofibers elicit adjuvant-free CD8(+) T cell responses. Vaccine. 2014, 32 (10): 1174-1180. 10.1016/j.vaccine.2013.11.047.PubMedCrossRef

20.

Xu Y, Tang H, Liu JH, Wang H, Liu Y: Evaluation of the adjuvant effect of silver nanoparticles both in vitro and in vivo. Toxicol Lett. 2013, 219 (1): 42-48. 10.1016/j.toxlet.2013.02.010.PubMedCrossRef

21.

Vono M, Taccone M, Caccin P, Gallotta M, Donvito G, Falzoni S, Palmieri E, Pallaoro M, Rappuoli R, Di Virgilio F, De Gregorio E, Montecucco C, Seubert A: The adjuvant MF59 induces ATP release from muscle that potentiates response to vaccination. Proc Natl Acad Sci U S A. 2013, 110 (52): 21095-21100. 10.1073/pnas.1319784110.PubMedPubMedCentralCrossRef

Title: GM-CSF-loaded chitosan hydrogel as an immunoadjuvant enhances antigen-specific immune responses with reduced toxicity
Authors: Kyung Hee Noh
Yeong Min Park
Hyuk Soon Kim
Tae Heung Kang
Kwon-Ho Song
Young-Ho Lee
Yeongseon Byeon
Hat Nim Jeon
In Duk Jung
Byung Cheol Shin
Kyung-Mi Lee
Seung-Yong Seong
Hee Dong Han
Tae Woo Kim
Publication date: 01-12-2014
Publisher: BioMed Central
Published in: BMC Immunology / Issue 1/2014
Electronic ISSN: 1471-2172
DOI: https://doi.org/10.1186/s12865-014-0048-x

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GM-CSF-loaded chitosan hydrogel as an immunoadjuvant enhances antigen-specific immune responses with reduced toxicity

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Background

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Results

Conclusions

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