Use of S-[2,3-bispalmitoyiloxy-(2R)-propyl]-R-cysteinyl-amido-monomethoxy polyethylene glycol as an adjuvant improved protective immunity associated with a DNA vaccine encoding Cu,Zn superoxide dismutase of Brucella abortus in mice

Clin Vaccine Immunol. 2014 Nov;21(11):1474-80. doi: 10.1128/CVI.00554-14. Epub 2014 Aug 27.

Abstract

This study was conducted to evaluate the immunogenicity and protective efficacy of a DNA vaccine encoding Brucella abortus Cu,Zn superoxide dismutase (SOD) using the Toll-like receptor 2/6 agonist S-[2,3-bispalmitoyiloxy-(2R)-propyl]-R-cysteinyl-amido-monomethoxy polyethylene glycol (BPPcysMPEG) as an adjuvant. Intranasal coadministration of BPPcysMPEG with a plasmid carrying the SOD-encoding gene (pcDNA-SOD) into BALB/c mice elicited antigen-specific humoral and cellular immune responses. Humoral responses were characterized by the stimulation of IgG2a and IgG1 and by the presence of SOD-specific secretory IgA in nasal and bronchoalveolar lavage fluids. Furthermore, T-cell proliferative responses and increased production of gamma interferon were also observed upon splenocyte restimulation with recombinant SOD. Cytotoxic responses were also stimulated, as demonstrated by the lysis of RB51-SOD-infected J774.A1 macrophages by cells recovered from immunized mice. The pcDNA-SOD/BPPcysMPEG formulation induced improved protection against challenge with the virulent strain B. abortus 2308 in BALB/c mice over that provided by pcDNA-SOD, suggesting the potential of this vaccination strategy against Brucella infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / administration & dosage*
  • Adjuvants, Immunologic / pharmacology
  • Administration, Intranasal
  • Animals
  • Antibodies, Bacterial / blood
  • Bacterial Proteins / genetics
  • Bacterial Proteins / immunology
  • Bronchoalveolar Lavage Fluid / immunology
  • Brucella Vaccine / administration & dosage
  • Brucella Vaccine / genetics
  • Brucella Vaccine / immunology*
  • Brucella abortus / enzymology*
  • Brucella abortus / genetics
  • Brucellosis / immunology
  • Brucellosis / prevention & control*
  • Cell Proliferation
  • Cytotoxicity Tests, Immunologic
  • Disease Models, Animal
  • Female
  • Immunoglobulin A, Secretory / analysis
  • Immunoglobulin G / blood
  • Interferon-gamma / metabolism
  • Macrophages / immunology
  • Macrophages / microbiology
  • Mice, Inbred BALB C
  • Nasal Mucosa / immunology
  • Polyethylene Glycols / administration & dosage*
  • Polyethylene Glycols / pharmacology
  • Spleen / immunology
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase / immunology*
  • T-Lymphocytes / immunology
  • Toll-Like Receptor 2 / agonists
  • Toll-Like Receptor 6 / agonists
  • Vaccines, DNA / administration & dosage
  • Vaccines, DNA / genetics
  • Vaccines, DNA / immunology*

Substances

  • Adjuvants, Immunologic
  • Antibodies, Bacterial
  • Bacterial Proteins
  • Brucella Vaccine
  • Immunoglobulin A, Secretory
  • Immunoglobulin G
  • Tlr2 protein, mouse
  • Tlr6 protein, mouse
  • Toll-Like Receptor 2
  • Toll-Like Receptor 6
  • Vaccines, DNA
  • Polyethylene Glycols
  • Interferon-gamma
  • Superoxide Dismutase