Preliminary evidence that the novel host-derived immunostimulant EP67 can act as a mucosal adjuvant

Clin Immunol. 2015 Dec;161(2):251-9. doi: 10.1016/j.clim.2015.06.006. Epub 2015 Jun 23.

Abstract

EP67 is a complement component 5a (C5a)-derived peptide agonist of the C5a receptor (CD88) that selectively activates DCs over neutrophils. Systemic administration of EP67 covalently attached to peptides, proteins, or attenuated pathogens generates TH1-biased immunogen-specific humoral and cellular immune responses with little inflammation. Furthermore, intranasal administration of EP67 alone increases the proportion of activated APCs in the airways. As such, we hypothesized that EP67 can act as a mucosal adjuvant. Intranasal immunization with an EP67-conjugated CTL peptide vaccine against protective MCMV epitopes M84 and pp89 increased protection of naïve female BALB/c mice against primary respiratory infection with salivary gland-derived MCMV and generated higher proportions of epitope responsive and long-lived memory precursor effector cells (MPEC) in the lungs and spleen compared to an inactive, scrambled EP67-conjugated CTL peptide vaccine and vehicle alone. Thus, EP67 may be an effective adjuvant for mucosal vaccines and warrants further study.

Keywords: Host-derived adjuvant; Mucosal adjuvant.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Administration, Intranasal
  • Amino Acid Sequence
  • Animals
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / virology
  • Cells, Cultured
  • Epitopes / immunology
  • Female
  • Flow Cytometry
  • Herpesviridae Infections / immunology*
  • Herpesviridae Infections / prevention & control
  • Herpesviridae Infections / virology
  • Host-Pathogen Interactions / immunology
  • Immunity, Mucosal / drug effects
  • Immunity, Mucosal / immunology*
  • Lung / immunology
  • Lung / virology
  • Mice
  • Mice, Inbred BALB C
  • Muromegalovirus / immunology*
  • Muromegalovirus / physiology
  • NIH 3T3 Cells
  • Oligopeptides / administration & dosage
  • Oligopeptides / immunology*
  • Salivary Glands / immunology
  • Salivary Glands / virology
  • Spleen / immunology
  • Spleen / virology
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Cytotoxic / virology
  • Vaccination / methods
  • Vaccines, Subunit / administration & dosage
  • Vaccines, Subunit / immunology*

Substances

  • Adjuvants, Immunologic
  • Epitopes
  • Oligopeptides
  • Vaccines, Subunit
  • tyrosyl-seryl-phenylalanyl-lysyl-aspartyl-methionyl-prolyl-N-methyleucyl-alanyl-arginine