Synergistic antibody induction by antigen-CD40 ligand fusion protein as improved immunogen

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Abstract

Full scale B-cell activation requires not only B-cell receptor (BCR) engagement with antigen, but also costimulatory signals provided by T helper cells through the CD40-CD40 ligand (CD40L) interaction. It is hypothesized that a fusion protein of an antigen and soluble CD40L (CD40LT) would selectively target the costimulation to antigen-specific B cells, leading to synergy in the antibody response. This hypothesis was investigated by fusing green fluorescence protein (GFP), a generic antigen, with mouse CD40LT. Studies revealed that immunization in mice with the plasmid encoding GFP-CD40LT fusion protein led to synergistic induction of GFP-specific antibodies, while control plasmid(s) for GFP, CD40LT, or GFP plus CD40LT did not. Immunization with a single dose of the fusion protein also provoked a vigorous GFP-specific immunoglobulin G1 antibody response, but not other antibody isotypes. These results suggest that GFP-CD40LT fusion protein induces a GFP-specific B-cell activation and antibody response in an antigen-guided fashion. The potential application of this novel strategy in vaccine development is discussed.

Original languageEnglish (US)
Pages (from-to)215-222
Number of pages8
JournalImmunology
Volume115
Issue number2
DOIs
StatePublished - Jun 1 2005

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Keywords

  • Antibody
  • B lymphocyte
  • CD40
  • CD40L
  • Fusion protein

ASJC Scopus subject areas

  • Immunology

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