The Carbomer-Lecithin Adjuvant Adjuplex Has Potent Immunoactivating Properties and Elicits Protective Adaptive Immunity against Influenza Virus Challenge in Mice

Clin Vaccine Immunol. 2015 Sep;22(9):1004-12. doi: 10.1128/CVI.00736-14. Epub 2015 Jul 1.

Abstract

The continued discovery and development of adjuvants for vaccine formulation are important to safely increase potency and/or reduce the antigen doses of existing vaccines and tailor the adaptive immune response to newly developed vaccines. Adjuplex is a novel adjuvant platform based on a purified lecithin and carbomer homopolymer. Here, we analyzed the adjuvant activity of Adjuplex in mice for the soluble hemagglutinin (HA) glycoprotein of influenza A virus. The titration of Adjuplex revealed an optimal dose of 1% for immunogenicity, eliciting high titers of HA-specific IgG but inducing no significant weight loss. At this dose, Adjuplex completely protected mice from an otherwise lethal influenza virus challenge and was at least as effective as the adjuvants monophosphoryl lipid A (MPL) and alum in preventing disease. Adjuplex elicited balanced Th1-/Th2-type immune responses with accompanying cytokines and triggered antigen-specific CD8(+) T-cell proliferation. The use of the peritoneal inflammation model revealed that Adjuplex recruited dendritic cells (DCs), monocytes, and neutrophils in the context of innate cytokine and chemokine secretion. Adjuplex neither triggered classical maturation of DCs nor activated a pathogen recognition receptor (PRR)-expressing NF-κB reporter cell line, suggesting a mechanism of action different from that reported for classical pathogen-associated molecular pattern (PAMP)-activated innate immunity. Taken together, these data reveal Adjuplex to be a potent and well-tolerated adjuvant with application for subunit vaccines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acrylic Resins
  • Adaptive Immunity*
  • Adjuvants, Immunologic* / administration & dosage
  • Animals
  • Antibodies, Viral / biosynthesis
  • Antibodies, Viral / immunology
  • B-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Cytokines / immunology
  • Cytokines / metabolism
  • Dendritic Cells / immunology
  • Hemagglutinin Glycoproteins, Influenza Virus / immunology*
  • Influenza A Virus, H1N1 Subtype / immunology*
  • Influenza Vaccines / administration & dosage
  • Influenza Vaccines / immunology*
  • Lecithins / immunology
  • Mice, Inbred BALB C
  • Orthomyxoviridae Infections / immunology
  • Orthomyxoviridae Infections / prevention & control*
  • Pathogen-Associated Molecular Pattern Molecules
  • Th1-Th2 Balance
  • Vaccination

Substances

  • Acrylic Resins
  • Adjuvants, Immunologic
  • Antibodies, Viral
  • Cytokines
  • H1N1 virus hemagglutinin
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Influenza Vaccines
  • Lecithins
  • Pathogen-Associated Molecular Pattern Molecules
  • carbomer