Just-in-time vaccines: Biomineralized calcium phosphate core-immunogen shell nanoparticles induce long-lasting CD8(+) T cell responses in mice

Nanomedicine. 2014 Apr;10(3):571-8. doi: 10.1016/j.nano.2013.11.007. Epub 2013 Nov 22.

Abstract

Distributed and on-demand vaccine production could be game-changing for infectious disease treatment in the developing world by providing new therapeutic opportunities and breaking the refrigeration "cold chain". Here, we show that a fusion protein between a calcium phosphate binding domain and the model antigen ovalbumin can mineralize a biocompatible adjuvant in a single step. The resulting 50 nm calcium phosphate core-immunogen shell particles are comparable to soluble protein in inducing ovalbumin-specific antibody response and class switch recombination in mice. However, single dose vaccination with nanoparticles leads to higher expansion of ovalbumin-specific CD8(+) T cells upon challenge with an influenza virus bearing the ovalbumin-derived SIINFEKL peptide, and these cells produce high levels of IFN-γ. Furthermore, mice exhibit a robust antigen-specific CD8(+) T cell recall response when challenged with virus 8 months post-immunization. These results underscore the promise of immunogen-controlled adjuvant mineralization for just-in-time manufacturing of effective T cell vaccines.

From the clinical editor: This paper reports that a fusion protein between a calcium phosphate binding domain and the model antigen ovalbumin can mineralize into a biocompatible adjuvant in a single step, enabling distributed and on-demand vaccine production and eliminating the need for refrigeration of vaccines. The findings highlight the possibility of immunogen-controlled adjuvant mineralization for just-in-time manufacturing of effective T cell vaccines.

Keywords: Biomineralization; Nanocarrier; Nanovaccine; Solid binding peptide.

Publication types

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

MeSH terms

  • Adjuvants, Immunologic / administration & dosage*
  • Adjuvants, Immunologic / metabolism
  • Adjuvants, Immunologic / pharmacology
  • Animals
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology
  • Calcium Phosphates / metabolism*
  • Chickens
  • Female
  • Humans
  • Mice
  • Nanoparticles / metabolism*
  • Ovalbumin / administration & dosage*
  • Ovalbumin / immunology
  • Ovalbumin / metabolism
  • Recombinant Fusion Proteins / administration & dosage*
  • Recombinant Fusion Proteins / immunology
  • Recombinant Fusion Proteins / metabolism
  • Vaccination
  • Vaccines / administration & dosage*
  • Vaccines / immunology
  • Vaccines / metabolism

Substances

  • Adjuvants, Immunologic
  • Calcium Phosphates
  • Recombinant Fusion Proteins
  • Vaccines
  • Ovalbumin
  • calcium phosphate