Enhancement of in vivo and in vitro immune functions by a conformationally biased, response-selective agonist of human C5a: implications for a novel adjuvant in vaccine design.
A conformationally biased, agonist of human C5a(65-74) (EP67) was assessed for its adjuvant activities in vitro and in 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 response in vitro. These results indicate the ability of EP67 to drive a Th1-mediated immune response and its potential use as a unique adjuvant.
Morgan
Edward L
EL
San Diego State University BioSciences Center, 5500 Campanile Drive, San Diego, CA 92182-4650b, United States. emorgan@sciences.sdsu.edu
Morgan
Brandon N
BN
Stein
Elisabeth A
EA
Vitrs
Elizabeth L
EL
Thoman
Marilyn L
ML
Sanderson
Sam D
SD
Phillips
Joy A
JA
D000276:Adjuvants, Immunologic / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D015936:Complement C5a / Q000819:agonists*; D005260:Female; D006001:Glycoconjugates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007107:Immune System / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D014612:Vaccines / Q000737:chemistry / Q000276:immunology*
D000276:Adjuvants, Immunologic; D006001:Glycoconjugates; D014612:Vaccines; D015936:Complement C5a