Meningococcal PorB induces a robust and diverse antigen specific T cell response as a vaccine adjuvant

Vaccine. 2018 Nov 29;36(50):7689-7699. doi: 10.1016/j.vaccine.2018.10.074. Epub 2018 Oct 28.

Abstract

Vaccines formulated with adjuvant have been effective against numerous infectious diseases, almost always due to induction of functional antibodies that recognizes the pathogen of interest. There is an unmet clinical need for vaccine adjuvants that induce T cells responses to potentially enhance protection against malignancies and intracellular pathogens, where a humoral response, alone, may not be adequate for protection. In this study, we demonstrate that a TLR2 ligand-based adjuvant, meningococcal PorB, has broad immunostimulatory activity with the ability to induce a robust and diverse vaccine antigen specific T cell response. We demonstrate that a vaccine formulated with PorB admixed with ovalbumin induces a wide variety of antigen specific antibody subclasses and effector molecules (MIG, MCP-1, IP-10, MIP-1α, KC & IL-2) with known roles for inducing T cell responses, along with elevated levels of Th1 and Th2 type cytokines upon antigen stimulation. We confirmed production of these cytokines by examining the antigen-specific T cells induced by PorB in vivo. After two immunizations with vaccine formulated with PorB/OVA, antigen-specific CD4 and CD8 T cells were significantly increased in numbers and produced IL-4 or IFN-γ upon ex vivo antigen re-stimulation. Finally, in a Listeria mouse infection model, vaccine formulated with PorB significantly reduced the bacterial burden upon a low dose infection and increased survival upon a high dose infection with recombinant Listeria monocytogenes engineered to express OVA (rLmOVA), a pathogen that requires OVA-antigen specific cytotoxic CD8 T cells for clearance. In summary, PorB is able to induce antigen specific broad B and T cell responses, illustrating its potential as a potent and new vaccine adjuvant.

Keywords: Adjuvant; MyD88; Neisseria meningitidis; PorB; T-cell; TLR; Vaccines.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / administration & dosage*
  • Animals
  • Bacterial Load
  • Bacterial Vaccines / administration & dosage
  • Bacterial Vaccines / immunology
  • Cytokines / analysis
  • Disease Models, Animal
  • Immunity, Cellular*
  • Listeria monocytogenes / isolation & purification
  • Listeriosis / pathology
  • Listeriosis / prevention & control
  • Mice, Inbred C57BL
  • Ovalbumin / administration & dosage
  • Ovalbumin / immunology*
  • Porins / administration & dosage*
  • T-Lymphocytes / immunology*
  • Vaccines, Subunit / administration & dosage
  • Vaccines, Subunit / immunology

Substances

  • Adjuvants, Immunologic
  • Bacterial Vaccines
  • Cytokines
  • Porins
  • Vaccines, Subunit
  • porin protein, Neisseria
  • Ovalbumin