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Modified chitosan-based nanoadjuvants enhance immunogenicity of protein antigens after mucosal vaccination.

Authors
  • Sinani, Genada1
  • Sessevmez, Melike2
  • Gök, M Koray3
  • Özgümüş, Saadet3
  • Alpar, H Oya4
  • Cevher, Erdal5
  • 1 Department of Pharmaceutical Technology, School of Pharmacy, Altinbas University, 34144 Istanbul, Turkey; Department of Pharmaceutical Technology, Faculty of Pharmacy, Istanbul University, 34116 Istanbul, Turkey. , (Turkey)
  • 2 Department of Pharmaceutical Technology, Faculty of Pharmacy, Istanbul University, 34116 Istanbul, Turkey. , (Turkey)
  • 3 Department of Chemical Engineering, Faculty of Engineering, Istanbul University-Cerrahpaşa, 34320 Istanbul, Turkey. , (Turkey)
  • 4 Department of Pharmaceutical Technology, School of Pharmacy, Altinbas University, 34144 Istanbul, Turkey; School of Pharmacy, University College London (UCL), WC1N 1AX London, UK. , (Turkey)
  • 5 Department of Pharmaceutical Technology, Faculty of Pharmacy, Istanbul University, 34116 Istanbul, Turkey. Electronic address: [email protected] , (Turkey)
Type
Published Article
Journal
International journal of pharmaceutics
Publication Date
Oct 05, 2019
Volume
569
Pages
118592–118592
Identifiers
DOI: 10.1016/j.ijpharm.2019.118592
PMID: 31386881
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Nasal vaccination is considered to be an effective and convenient way of increasing immune responses both systemically and locally. Although various nanovaccine carriers have been introduced as potential immune adjuvants, further improvements are still needed before they can be taken to clinical usage. Chitosan-based nanovaccine carriers are one of the most widely studiedadjuvants, owing to the abilityof chitosan toopen tight junctions between nasal epithelial cells and enhance particle uptake as well as its inherent immune activating role. In present study, bovine serum albumin (BSA) loaded nanoparticles were prepared using novel aminated (aChi) and aminated plus thiolated chitosan (atChi) polymers, to further enhance mucoadhesiveness and adjuvanticity of the vaccine system by improving electrostatic interactions of polymers with negatively charged glycoproteins. Nanocarriers with optimum size and surface charge, high encapsulation efficiency of model antigen and good stability were developed. Negligible toxicity was observed in Calu-3 and A549 cell lines. In vivo studies, revealed high levels of systemic antibodies (IgG, IgG1 and IgG2a) throughout the study and presence of sIgA in vaginal washes showed that common mucosal system was successfully stimulated. Cytokine levels indicated a mixed Th1/Th2 immune response. A shift towards cellular immune responses was observed after nasal immunisation with antigen loaded nanoparticle formulations. These nanoparticles exhibit great potential for nasal application of vaccines. Copyright © 2019 Elsevier B.V. All rights reserved.

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