title: Polarized immune responses modulated by layered double hydroxides nanoparticle conjugated with CpG.
abstract: Modulation of the immune response is an important step in the induction of protective humoral and cellular immunity against pathogens. In this study, we investigated the possibility of using a nanomaterial conjugated with the toll-like receptor (TLR) ligand CpG to modulate the immune response towards the preferred polarity. MgAl-layered double hydroxide (LDH) nanomaterial has a very similar chemical composition to Alum, an FDA approved adjuvant for human vaccination. We used a model antigen, ovalbumin (OVA) to demonstrate that MgAl-LDH had comparable adjuvant activity to Alum, but much weaker inflammation. Conjugation of TLR9 ligand CpG to LDH nanoparticles significantly enhanced the antibody response and promoted a switch from Th2 toward Th1 response, demonstrated by a change in the IgG2a:IgG1 ratio. Moreover, immunization of mice with CpG-OVA-conjugated LDH before challenge with OVA-expressing B16/F10 tumor cells retarded tumor growth. Together, these data indicate that LDH nanomaterial can be used as an immune adjuvant to promote Th1 or Th2 dominant immune responses suitable for vaccination purposes.
authors.affiliation: Australian Institute for Bioengineering and Nanotechnology, University of Queensland, St Lucia, QLD 4072, Australia.
authors.forename: Shiyu
authors.initials: S
authors.lastname: Yan
authors.affiliation: Australian Institute for Bioengineering and Nanotechnology, University of Queensland, St Lucia, QLD 4072, Australia.
authors.forename: Barbara E
authors.initials: BE
authors.lastname: Rolfe
authors.affiliation: Vaccine Delivery, Animal Science, Agri-Science Queensland Department of Agriculture, Fisheries and Forestry, St Lucia, QLD 4067, Australia.
authors.forename: Bing
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Therapeutics Research Centre, School of Medicine, Princess Alexandra Hospital, University of Queensland, Woolloongabba, QLD 4102, Australia.
authors.forename: Yousuf H
authors.initials: YH
authors.lastname: Mohammed
authors.affiliation: Australian Institute for Bioengineering and Nanotechnology, University of Queensland, St Lucia, QLD 4072, Australia. Electronic address: w.gu@uq.edu.au.
authors.forename: Wenyi
authors.initials: W
authors.lastname: Gu
authors.affiliation: Australian Institute for Bioengineering and Nanotechnology, University of Queensland, St Lucia, QLD 4072, Australia. Electronic address: gordonxu@uq.eud.au.
authors.forename: Zhi P
authors.initials: ZP
authors.lastname: Xu
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000534:Alum Compounds / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D045744:Cell Line, Tumor; D055598:Chemical Phenomena; D018899:CpG Islands; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D005260:Female; D006878:Hydroxides / Q000737:chemistry / Q000494:pharmacology; D007111:Immunity, Cellular / Q000187:drug effects; D007114:Immunization; D007074:Immunoglobulin G / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000737:chemistry*; D010047:Ovalbumin / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D006878:Hydroxides; D007074:Immunoglobulin G; C041524:aluminum sulfate; D010047:Ovalbumin; C031356:hydroxide ion
keywords: Immunity polarization; Layered double hydroxide nanomaterial; Nanoadjuvant; Th1 and Th2 immune responses; Toll-like receptor (TLR) ligand CpG