title: Just-in-time vaccines: Biomineralized calcium phosphate core-immunogen shell nanoparticles induce long-lasting CD8(+) T cell responses in mice.
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.
  
  
  BACKGROUND
  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.
authors.affiliation: Department of Chemical Engineering, University of Washington, Seattle, WA, USA.
authors.forename: Weibin
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Department of Immunology, University of Washington, Seattle, WA, USA.
authors.forename: Albanus O
authors.initials: AO
authors.lastname: Moguche
authors.affiliation: Department of Chemical Engineering, University of Washington, Seattle, WA, USA; Department of Bioengineering, University of Washington, Seattle, WA, USA.
authors.forename: David
authors.initials: D
authors.lastname: Chiu
authors.affiliation: Department of Immunology, University of Washington, Seattle, WA, USA.
authors.forename: Kaja
authors.initials: K
authors.lastname: Murali-Krishna
authors.affiliation: Department of Chemical Engineering, University of Washington, Seattle, WA, USA; Department of Bioengineering, University of Washington, Seattle, WA, USA. Electronic address: baneyx@uw.edu.
authors.forename: François
authors.initials: F
authors.lastname: Baneyx
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002130:Calcium Phosphates / Q000378:metabolism*; D002645:Chickens; D005260:Female; D006801:Humans; D051379:Mice; D053758:Nanoparticles / Q000378:metabolism*; D010047:Ovalbumin / Q000008:administration & dosage* / Q000276:immunology / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage* / Q000276:immunology / Q000378:metabolism; D014611:Vaccination; D014612:Vaccines / Q000008:administration & dosage* / Q000276:immunology / Q000378:metabolism
chemical_list: D000276:Adjuvants, Immunologic; D002130:Calcium Phosphates; D011993:Recombinant Fusion Proteins; D014612:Vaccines; D010047:Ovalbumin; C020243:calcium phosphate
keywords: Biomineralization; Nanocarrier; Nanovaccine; Solid binding peptide