Enhancement ofin vivoandin vitroimmune 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 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...

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Bibliographic Details
Published inVaccine 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
LanguageEnglish
Published Kidlington Elsevier Limited 11.12.2009
Subjects
Antigens
Bias
Cytokines
Design
Hypotheses
Immune response
Immune system
Immunization
Laboratories
Ligands
Lymphocytes
Peptides
Proteins
Vaccines
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Summary: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.
ISSN:0264-410X
1873-2518
DOI:10.1016/j.vaccine.2009.10.029