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

Vaccine. 2009 Dec 11;28(2):463-9. doi: 10.1016/j.vaccine.2009.10.029. Epub 2009 Oct 15.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adjuvants, Immunologic / chemical synthesis
  • Adjuvants, Immunologic / chemistry
  • Adjuvants, Immunologic / pharmacology*
  • Animals
  • Complement C5a / agonists*
  • Female
  • Glycoconjugates / chemical synthesis
  • Glycoconjugates / chemistry
  • Glycoconjugates / pharmacology*
  • Humans
  • Immune System / drug effects
  • Mice
  • Mice, Inbred C57BL
  • Vaccines / chemistry
  • Vaccines / immunology*

Substances

  • Adjuvants, Immunologic
  • Glycoconjugates
  • Vaccines
  • Complement C5a