Polymeric hepatitis C virus non-structural protein 5A nanocapsules induce intrahepatic antigen-specific immune responses

Michael Fichter, Keti Piradashvili, Anette Pietrzak-Nguyen, Leah Pretsch, Gabor Kuhn, Susanne Strand, Markus Knuf, Fred Zepp, Frederik R. Wurm, Volker Mailänder, Katharina Landfester, Stephan Gehring*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

6 Citations (Scopus)

Abstract

Targeting antigen combined with adjuvants to hepatic antigen-presenting cells (APCs) is essential for the induction of intrahepatic T cellular immunity controlling and resolving viral infections of the liver. Intravenous injection of antigen-loaded nanoparticles is a promising approach for the delivery of antigens to liver APCs. Accordingly, polymeric nanocapsules (NCs) synthesized exclusively of hepatitis C virus non-structural protein 5A (NS5A) and the adjuvant monophosphoryl lipid A (MPLA) adsorbed to the nanocapsule surface were developed. Aim of the present study was the evaluation of the in vitro and in vivo behavior of MPLA-functionalized NS5A-NCs regarding the interaction with liver dendritic cells (DCs) and the potential to induce intrahepatic immune responses in a mouse model. Maturation of DCs was significantly increased by application of NS5A+MPLA-NCs compared to non-functionalized NS5A-NCs promoting a vigorous expression of CD40, CD80, CD86 and a strong secretion of the Th1-related cytokine IL-12. NS5A-NCs were preferentially deposited in DCs and Kupffer cells residing in the liver after intravenous administration. Immunization with NS5A-NCs induced intrahepatic antigen-specific CD4+ T cellular immune responses determined by the secretion of IFNγ and IL-2. Furthermore, supplementation with MPLA induced significant levels of NS5A-specific antibodies. The application of polymeric nanocapsules synthesized exclusively out of antigen avoids the risk of unintended side effects caused by additional carrier substances. Functionalization with adjuvants like MPLA and the efficient targeting to liver-resident APCs inherits the potential for application of antigen nanocapsules in further vaccination approaches against pathogens affecting the liver.

Original languageEnglish
Pages (from-to)1-12
Number of pages12
JournalBiomaterials
Volume108
DOIs
Publication statusPublished - 1 Nov 2016
Externally publishedYes

Keywords

  • HCV NS5A
  • Immunization
  • MPLA
  • Nanocapsules
  • Vaccination

Fingerprint Dive into the research topics of 'Polymeric hepatitis C virus non-structural protein 5A nanocapsules induce intrahepatic antigen-specific immune responses'. Together they form a unique fingerprint.

Cite this