A novel adjuvant for vaccine development in the aged.
A conformationally-biased, response-selective agonist of human C5a(65-74) (EP67) activated antigen presenting cells (APC) from aged C57Bl/6 mice in vitro and the generation of antigen (Ag)-specific antibody (Ab) responses in aged mice in vivo. EP67, induced the release of the pro-inflammatory cytokines IL-6, TNFα, and INFγ from splenic APCs obtained from both aged and young mice. Both aged and young mice produced high Ag-specific IgG Ab titers when immunized with EP67-containing vaccines to ovalbumin (OVA-EP67) and to a protein (rPrp1) from the cell wall of Coccidioides (rPrp1-EP67). Immunization with EP67-containing vaccines resulted in higher IgG titers in both young and aged mice compared to mice immunized with OVA adsorbed to alum (OVA/alum) and Prp1 admixed with CpG (rPrp1 +CpG). Aged and young mice immunized with the EP67-containing vaccines generated higher titers of IgG1 and IgG2b relative to their aged-matched counterparts immunized with OVA/alum or Prp1 +CpG. These results indicate that EP67 induces humoral immunity in aged mice not obtainable with alum and CpG. These results support the use of EP67 as a potential vaccine adjuvant suited to the elderly.
Morgan
Edward L
EL
San Diego State University, Biosciences Center, 5500 Campanile Drive, San Diego, CA 92182, USA. emorgan@sciences.sdsu.edu
Thoman
Marilyn L
ML
Sanderson
Sam D
SD
Phillips
Joy A
JA
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000375:Aging; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D000946:Antigens, Fungal / Q000276:immunology*; D003045:Coccidioides / Q000276:immunology; D015936:Complement C5a / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000276:Adjuvants, Immunologic; D000946:Antigens, Fungal; D007074:Immunoglobulin G; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D015936:Complement C5a; D007371:Interferon-gamma; D010047:Ovalbumin