Fluorinated Lipids Conjugated to Peptide Antigens do not Induce Immune Responses Against Cervical Cancer

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Authors

  • Waleed M. Hussein School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD 4072, Australia; Helwan University, Faculty of Pharmacy, Pharmaceutical Organic Chemistry Department, Ein Helwan, Egypt
  • Saori Mukaida School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD 4072, Australia
  • Tzu-Yu Liu School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD 4072, Australia
  • Istvan Toth School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD 4072, Australia; Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD 4072, Australia; School of Pharmacy, The University of Queensland, Brisbane, QLD 4102, Australia
  • Mariusz Skwarczynski School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD 4072, Australia

DOI:

https://doi.org/10.17140/VROJ-2-107

Keywords:

Fluorinated lipid, Self-adjuvant, Cellular immunity, Peptide-based vaccine, Nanoparticle

Abstract

Background: Despite the high safety profile of peptide-based vaccines over conventional counterparts, the inability of small peptides to produce a strong immune response represents the main obstacle for the development of these types of vaccines. Introducing a self-adjuvanting moiety such as fluorinated lipids can overcome this problem. We have recently demonstrated that fluorinated lipids can induce humoral immune responses against associated peptide antigen; however, the ability of these amphiphilic lipids to elicit a desired cellular immune response to eradicate tumor cells has not been yet investigated.
Methods: An in vivo assay was employed to evaluate the ability of fluorinated lipopeptides to eradicate tumor in mouse model. In this study, the double conjugation technique was used to synthesise fluorinated and non-fluorinated lipids conjugated to two cytotoxic T-lymphocyte (CTL) peptide epitopes derived from the E6 and E7 proteins of human papilloma virus (HPV).
Results: Mice implanted with TC-1 tumor cells and immunised with fluorinated lipopeptides did not mount a strong cellular immune response, thus did not eradicate the tumors. In contrast, 60% of mice immunised with the non-fluorinated lipopeptide cleared the TC-1 tumor.
Conclusion: This result indicated that fluorinated lipids lack of the ability to stimulate a strong cellular immunity despite their ability to elicit significant humoral immune responses.

References

Skwarczynski M, Toth I. Peptide-based synthetic vaccines. Chem Sci. 2016; 7(2): 842-854. doi: 10.1039/c5sc03892h

Reed SG, Orr MT, Fox CB. Key roles of adjuvants in mod-ern vaccines. Nat Med. 2013; 19(12): 1597-1608. doi: 10.1038/ Nm.3409

Azmi F, Fuaad AAA, Skwarczynski M, et al. Recent prog-ress in adjuvant discovery for peptide-based subunit vaccines. Hum Vaccin Immunother. 2014; 10(3): 778-796. doi: 10.4161/ hv.27332

Zaman M, Toth I. Immunostimulation by synthetic lipopep-tide-based vaccine candidates: Structure-activity relationships. Front Immunol. 2013; 4: 318. doi: 10.3389/fimmu.2013.00318

Hussein WM, Mukaida S, Azmi F, et al. Comparison of fluo-rinated and nonfluorinated lipids in self-adjuvanting delivery systems for peptide-based vaccines. Acs Med Chem Lett. 2017; 8(2): 227-232. doi: 10.1021/acsmedchemlett.6b00453

Hussein WM, Liu TY, Maruthayanar P, et al. Double con-jugation strategy to incorporate lipid adjuvants into multianti-genic vaccines. Chem Sci. 2016; 7(3): 2308-2321. doi: 10.1039/ c5sc03859f

Liu TY, Hussein WM, Toth I, et al. Advances in peptide-based human papillomavirus therapeutic vaccines. Curr Top Med Chem. 2012; 12(14): 1581-1592.

Sarkar AK, Tortolero-Luna G, Nehete PN, et al. Studies on in vivo induction of cytotoxic T lymphocyte responses by synthetic peptides from E6 and E7 oncoproteins of human papillomavirus type 16. Viral immunology. 1995; 8(3): 165-174.

Liu TY, Hussein WM, Jia Z, et al. Self-adjuvanting polymer-peptide conjugates as therapeutic vaccine candidates against cer-vical cancer. Biomacromolecules 2013; 14(8): 2798-2806. doi:

1021/bm400626w 10. Villada IB, Barracco MM, Berville S, et al. Human papil-lomavirus 16-specific T-cell responses in classic HPV-related vulvar intra-epithelial neoplasia. Determination of strongly im-munogenic regions from E6 and E7 proteins. Clin Exp Immunol. 2010; 159(1): 45-56. doi: 10.1111/j.1365-2249.2009.04006.x

Liu TY, Hussein WM, Giddam AK, et al. Polyacrylate-based delivery system for self-adjuvanting anticancer peptide vaccine. J Med Chem. 2015; 58(2): 888-896. doi: 10.1021/Jm501514h

Liu TY, Giddam AK, Hussein WM, et al. Self-adjuvanting therapeutic peptide-based vaccine induce CD8(+) iytotoxic T lymphocyte responses in a murine human papilloma virus tumor model. Current drug delivery. 2015; 12(1): 3-8. doi: 10.2174/15 67201811666141001155729

Skwarczynski M, Zaman M, Urbani CN, et al. Polyacry-late dendrimer nanoparticles: A self-adjuvanting vaccine de-livery system. Angew Chem Int Ed. 2010; 49(33): 5742-5745, S5742/5741-S5742/5714. doi: 10.1002/anie.201002221

Azmi F, Fuaad AAA, Giddam AK, et al. Self-adjuvanting vaccine against group A streptococcus: Application of fi-brillized peptide and immunostimulatory lipid as adjuvant. Bioorg Med Chem. 2014; 22(22): 6401-6408. doi: 10.1016/j. bmc.2014.09.042

Tang J, Yin R, Tian Y, et al. A novel self-assembled nanopar-ticle vaccine with HIV-1 Tat/HPV16 E7 fusion peptide and GM-CSF DNA elicits potent and prolonged CD8 T cell-dependent anti-tumor immunity in mice. Vaccine. 2012; 30(6): 1071-1082. doi: 10.1016/j.vaccine.2011.12.029

Hussein WM, Liu TY, Jia ZF, et al. Multiantigenic peptide-polymer conjugates as therapeutic vaccines against cervical can-cer. Bioorg Med Chem. 2016; 24(18): 4372-4380. doi: 10.1016/j. bmc.2016.07.036

Mottram PL, Leong D, Crimeen-Irwin B, et al. Type 1 and 2 immunity following vaccination is influenced by nanoparti-cle size: Formulation of a model vaccine for respiratory syn-cytial virus. Molecular Pharmaceutics. 2007; 4(1): 73-84. doi: 10.1021/mp060096p

Nixon DF, Hioe C, Chen PD, et al. Synthetic peptides en-trapped in microparticles can elicit cytotoxic T cell activ-ity. Vaccine. 1996; 14(16): 1523-1530. doi: 10.1016/S0264- 410x(96)00099-0

Alexander M, Salgaller ML, Celis E, et al. Generation of tumor-specific cytolytic T lymphocytes from peripheral blood of cervical cancer patients by in vitro stimulation with a synthetic human papillomavirus type 16 E7 epitope. Am J Obstet Gynecol. 1996; 175(6): 1586-1593.

Hung C-F, Cheng W-F, Chai C-Y, et al. Improving vaccine potency through intercellular spreading and enhanced MHC class I presentation of antigen. J Immunol. 2001; 166: 5733- 5740. doi: 10.1016/S0002-9378(96)70110-2

Zeng Q, Peng S, Monie A, et al. Control of cervicovaginal HPV-16 E7-expressing tumors by the combination of therapeu-tic HPV vaccination and vascular disrupting agents. Hum Gene Ther. 2011; 22(7): 809-819. doi: 10.1089/hum.2010.071

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Published

2017-06-09

How to Cite

Waleed M. Hussein, Saori Mukaida, Tzu-Yu Liu, Istvan Toth, & Mariusz Skwarczynski. (2017). Fluorinated Lipids Conjugated to Peptide Antigens do not Induce Immune Responses Against Cervical Cancer. Vaccination Research, 2(1), 7–12. https://doi.org/10.17140/VROJ-2-107

Issue

Vol. 2 No. 1 (2017): Volume 2 Issue 1 2017

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Articles

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