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

Edward L. Morgan; Brandon N. Morgan; Elisabeth A. Stein; Elizabeth L. Vitrs; Marilyn L. Thoman; Sam D. Sanderson; Joy A. Phillips

doi:10.1016/j.vaccine.2009.10.029

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

Edward L. Morgan, Brandon N. Morgan, Elisabeth A. Stein, Elizabeth L. Vitrs, Marilyn L. Thoman, Sam D. Sanderson, Joy A. Phillips

Pharmaceutical Science

Research output: Contribution to journal › Article › peer-review

25 Scopus citations

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.

Original language	English (US)
Pages (from-to)	463-469
Number of pages	7
Journal	Vaccine
Volume	28
Issue number	2
DOIs	https://doi.org/10.1016/j.vaccine.2009.10.029
State	Published - Dec 11 2009

Keywords

Adjuvants
Antibodies
C5a
Vaccines

ASJC Scopus subject areas

Molecular Medicine
General Immunology and Microbiology
General Veterinary
Public Health, Environmental and Occupational Health
Infectious Diseases

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10.1016/j.vaccine.2009.10.029

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title = "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",

abstract = "A conformationally biased, agonist of human C5a65-74 (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.",

keywords = "Adjuvants, Antibodies, C5a, Vaccines",

author = "Morgan, {Edward L.} and Morgan, {Brandon N.} and Stein, {Elisabeth A.} and Vitrs, {Elizabeth L.} and Thoman, {Marilyn L.} and Sanderson, {Sam D.} and Phillips, {Joy A.}",

note = "Funding Information: The authors would like to thank Dr. Lu Bio, Harvard University for breeding pairs of C5L2 −/− mice and Ms. Laura Nelson for editorial assistance. This work was supported by NIH Grants 7R21AG031496-0308 (J.A.P.), 5R21AI065712-02 (J.A.P.) and 7RO1AG028077-03 (M.L.T.). ",

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AU - Stein, Elisabeth A.

AU - Vitrs, Elizabeth L.

AU - Thoman, Marilyn L.

AU - Sanderson, Sam D.

AU - Phillips, Joy A.

N1 - Funding Information: The authors would like to thank Dr. Lu Bio, Harvard University for breeding pairs of C5L2 −/− mice and Ms. Laura Nelson for editorial assistance. This work was supported by NIH Grants 7R21AG031496-0308 (J.A.P.), 5R21AI065712-02 (J.A.P.) and 7RO1AG028077-03 (M.L.T.).

PY - 2009/12/11

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N2 - A conformationally biased, agonist of human C5a65-74 (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.

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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

Abstract

Keywords

ASJC Scopus subject areas

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