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Front. Immunol. | doi: 10.3389/fimmu.2018.02968

Design of peptide-based nanovaccines targeting leading antigens from gynecological cancers to induce HLA-A2.1 restricted CD8+ T cell responses

 Sue D. Xiang1, 2*,  Kirsty L. Wilson1, Anne Goubier3, 4, Arne Heyerick3, 4 and  Magdalena Plebanski1, 5*
  • 1Monash University, Australia
  • 2Hudson Institute of Medical Research, Australia
  • 3PX Biosolutions Pty Ltd, Australia
  • 4Droia NV, Belgium
  • 5RMIT University, Australia

Gynecological cancers are a leading cause of mortality in women. CD8++ T cell immunity largely correlates with enhanced survival, whereas inflammation is associated with poor prognosis. Previous studies have shown polystyrene nanoparticles (PSNPs) are biocompatible, do not induce inflammation and when used as vaccine carriers for model peptides induce CD8+ T cell responses. Herein we test the immunogenicity of 24 different peptides, from three leading vaccine target proteins in gynecological cancers: the E7 protein of human papilloma virus (HPV); Wilms Tumor antigen 1 (WT1) and survivin (SV), in PSNP conjugate vaccines. Of relevance to vaccine development was the finding that a minimal CD8+ T cell peptide epitope from HPV was not able to induce HLA-A2.1 specific CD8+ T cell responses in transgenic humanized mice using conventional adjuvants such as CpG, but was nevertheless able to generate strong immunity when delivered as part of a specific longer peptide conjugated to PSNPs vaccines. Conversely, in most cases, when the minimal CD8+ T cell epitopes were able to induce immune responses (with WT1 or SV super agonists) in CpG, they also induced responses when conjugated to PSNPs. In this case, extending the sequence around the CD8+ T cell epitope, using the natural protein context, or engineering linker sequences proposed to enhance antigen processing, had minimal effects in enhancing or changing the cross-reactivity pattern induced by the super agonists. Nanoparticle approaches, such as PSNPs, therefore may offer an alternative vaccination strategy when conventional adjuvants are unable to elicit the desired CD8+ T cell specificity. The findings herein also offer sequence specific insights into peptide vaccine design for nanoparticle-based vaccine carriers.

Keywords: nanoparticle, HPV, WT1, survivin, CD8 T cell epitope, peptide, Nanovaccine

Received: 04 Oct 2018; Accepted: 03 Dec 2018.

Edited by:

Sandra Tuyaerts, KU Leuven, Belgium

Reviewed by:

Cristina Maccalli, Sidra Medical and Research Center, Qatar
Said Dermime, National Center for Cancer Care and Research, Qatar  

Copyright: © 2018 Xiang, Wilson, Goubier, Heyerick and Plebanski. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Dr. Sue D. Xiang, Monash University, Melbourne, Australia, sue.xiang@monash.edu
Prof. Magdalena Plebanski, RMIT University, Melbourne, 3000, Victoria, Australia, magdalena.plebanski@rmit.edu.au