A systems approach to designing next generation vaccines: combining α-galactose modified antigens with nanoparticle platforms.
Innovative vaccine platforms are needed to develop effective countermeasures against emerging and re-emerging diseases. These platforms should direct antigen internalization by antigen presenting cells and promote immunogenic responses. This work describes an innovative systems approach combining two novel platforms, αGalactose (αGal)-modification of antigens and amphiphilic polyanhydride nanoparticles as vaccine delivery vehicles, to rationally design vaccine formulations. Regimens comprising soluble αGal-modified antigen and nanoparticle-encapsulated unmodified antigen induced a high titer, high avidity antibody response with broader epitope recognition of antigenic peptides than other regimen. Proliferation of antigen-specific CD4(+) T cells was also enhanced compared to a traditional adjuvant. Combining the technology platforms and augmenting immune response studies with peptide arrays and informatics analysis provides a new paradigm for rational, systems-based design of next generation vaccine platforms against emerging and re-emerging pathogens.
1] Department of Veterinary Microbiology and Preventive Medicine, Iowa State University, Ames, IA 50011 [2].
Yashdeep
Y
Phanse
1] Department of Chemical and Biological Engineering, Iowa State University, Ames, IA 50011 [2].
Brenda R
BR
Carrillo-Conde
1] Department of Veterinary Microbiology and Preventive Medicine, Iowa State University, Ames, IA 50011 [2] Department of Food Science and Technology, University of Nebraska-Lincoln, Lincoln, NE 68583.
Amanda E
AE
Ramer-Tait
Department of Materials Science and Engineering, Iowa State University, Ames, IA 50011.
Scott
S
Broderick
Department of Materials Science and Engineering, Iowa State University, Ames, IA 50011.
Chang Sun
CS
Kong
Department of Materials Science and Engineering, Iowa State University, Ames, IA 50011.
Krishna
K
Rajan
BioProtection Systems Corporation, a subsidiary of NewLink Genetics Corporation, Ames, IA 50010.
Ramon
R
Flick
1] BioProtection Systems Corporation, a subsidiary of NewLink Genetics Corporation, Ames, IA 50010 [2].
Robert B
RB
Mandell
Department of Chemical and Biological Engineering, Iowa State University, Ames, IA 50011.
Balaji
B
Narasimhan
Department of Veterinary Microbiology and Preventive Medicine, Iowa State University, Ames, IA 50011.
Michael J
MJ
Wannemuehler
D000276:Adjuvants, Immunologic; D000938:Antigen-Presenting Cells / Q000276:immunology; D000941:Antigens / Q000276:immunology / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D053758:Nanoparticles / Q000737:chemistry* / Q000627:therapeutic use; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D049490:Systems Biology; D014612:Vaccines / Q000276:immunology*; D000519:alpha-Galactosidase / Q000276:immunology* / Q000627:therapeutic use
D000276:Adjuvants, Immunologic; D000941:Antigens; D000939:Epitopes; D010455:Peptides; D014612:Vaccines; D000519:alpha-Galactosidase