IgG-mediated anaphylaxis to a synthetic long peptide vaccine containing a B cell epitope can be avoided by slow-release formulation

J Immunol. 2014 Jun 15;192(12):5813-20. doi: 10.4049/jimmunol.1302337. Epub 2014 May 9.

Abstract

Synthetic long peptides (SLP) are a promising vaccine modality to induce therapeutic T cell responses in patients with chronic infections and tumors. We studied different vaccine formulations in mice using SLP derived from carcinoembryonic Ag. We discovered that one of the SLP contains a linear Ab epitope in combination with a CD4 epitope. Repeated vaccination with this carcinoembryonic Ag SLP in mice shows improved T cell responses and simultaneously induced high titers of peptide-specific Abs. These Abs resulted in unexpected anaphylaxis after a third or subsequent vaccinations with the SLP when formulated in saline. Administration of low SLP doses in the slow-release vehicle IFA prevented the anaphylaxis after repeated vaccination. This study underscores both the immunogenicity of SLP vaccination, for inducing T cell as well as B cell responses, and the necessity of safe administration routes.

MeSH terms

  • Anaphylaxis / immunology
  • Anaphylaxis / prevention & control*
  • Animals
  • Carcinoembryonic Antigen / immunology
  • Carcinoembryonic Antigen / pharmacology*
  • Delayed-Action Preparations / pharmacology
  • Epitopes, B-Lymphocyte / immunology
  • Epitopes, B-Lymphocyte / pharmacology*
  • Female
  • Immunoglobulin G / immunology*
  • Mice
  • Mice, Knockout
  • Peptides / immunology
  • Peptides / pharmacology*
  • Vaccination / methods
  • Vaccines / pharmacology*

Substances

  • Carcinoembryonic Antigen
  • Delayed-Action Preparations
  • Epitopes, B-Lymphocyte
  • Immunoglobulin G
  • Peptides
  • Vaccines