Synthetic melanin bound to subunit vaccine antigens significantly enhances CD8+ T-cell responses

PLoS One. 2017 Jul 17;12(7):e0181403. doi: 10.1371/journal.pone.0181403. eCollection 2017.

Abstract

Cytotoxic T-lymphocytes (CTLs) play a key role in immunity against cancer; however, the induction of CTL responses with currently available vaccines remains difficult. Because several reports have suggested that pigmentation and immunity might be functionally linked, we investigated whether melanin can act as an adjuvant in vaccines. Short synthetic peptides (8-35 amino acids long) containing T-cell epitopes were mixed with a solution of L-Dopa, a precursor of melanin. The mixture was then oxidized to generate nanoparticles of melanin-bound peptides. Immunization with melanin-bound peptides efficiently triggered CTL responses in mice, even against self-antigens and at a very low dose of peptides (microgram range). Immunization against a tumor antigen inhibited the growth of established tumors in mice, an effect that was abrogated by the depletion of CD8+ lymphocytes. These results demonstrate the efficacy of melanin as a vaccine adjuvant.

MeSH terms

  • Adjuvants, Immunologic*
  • Animals
  • Antigens, Neoplasm / chemistry
  • CD8-Positive T-Lymphocytes / immunology*
  • Cancer Vaccines / chemistry
  • Epitopes, T-Lymphocyte / chemistry
  • Epitopes, T-Lymphocyte / immunology*
  • Female
  • Immunization
  • Immunologic Memory
  • Lymph Nodes / immunology
  • Lymph Nodes / pathology
  • Melanins / chemical synthesis
  • Melanins / chemistry
  • Melanins / immunology*
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Neoplasm Transplantation
  • Neoplasms / immunology
  • Neoplasms / pathology
  • Neoplasms / therapy*
  • Oxidation-Reduction
  • Vaccines, Subunit / chemistry
  • Vaccines, Subunit / immunology

Substances

  • Adjuvants, Immunologic
  • Antigens, Neoplasm
  • Cancer Vaccines
  • Epitopes, T-Lymphocyte
  • Melanins
  • Vaccines, Subunit

Grants and funding

Funding support for this study was provided by: Oligocyte (non-profit association); ADNA (non-profit association). The authors received no other specific funding for this work.