Enhancement ofin vivoandin vitroimmune functions by a conformationally biased, response-selective agonist of human C5a: Implications for a novel adjuvant in vaccine design

• Published in: Vaccine Vol. 28; no. 2; p. 463
• Main Authors: Morgan, Edward L, Morgan, Brandon N, Stein, Elisabeth A, Vitrs, Elizabeth L, Thoman, Marilyn L, Sanderson, Sam D, Phillips, Joy A
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Limited 11.12.2009
• Subjects: Antigens; Bias; Cytokines; Design; Hypotheses; Immune response; Immune system; Immunization; Laboratories; Ligands; Lymphocytes; Peptides; Proteins; Vaccines
• DOI: 10.1016/j.vaccine.2009.10.029
• ISSN: 0264-410X

A conformationally biased, agonist of human C5a65-74(EP67) was assessed for its adjuvant activitiesin vitroandin vivo. EP67 induced the release of the inflammatory (Th1) type cytokines from C5a receptor (CD88)-bearing antigen presenting cells (APC). EP67 did not induce the release of these cytokines from splenic APCs obtained from C5a receptor knockouts (CD88-/-). Serum from mice immunized with EP67-ovalbumin (OVA) contained high OVA-specific antibody (Ab) titers [IgG1, IgG2a (IGg2c), IgG2b]. Mice receiving OVA alone produced only IgG1 Abs, indicating the ability of EP67 to induce a Th1-like Ab class switch. Spleen cell cultures from wild type mice but not CD88-/-mice showed an enhanced OVA-specific proliferative responsein vitro. These results indicate the ability of EP67 to drive a Th1-mediated immune response and its potential use as a unique adjuvant.