A soluble lymphocyte activation gene-3 molecule used as a vaccine adjuvant elicits greater humoral and cellular immune responses to both particulate and soluble antigens

J Immunol. 2000 Jun 1;164(11):5583-9. doi: 10.4049/jimmunol.164.11.5583.


The lymphocyte activation gene-3 (LAG-3) product is a MHC class II ligand that has been used in vivo to stimulate MHC class II+ APCs to increase tumor-specific immune responses. We investigated whether LAG-3 could also play an adjuvant role in vivo for the induction of humoral and CD4 or CD8 cell-mediated immune responses when immunizing mice with a particulate (hepatitis B surface Ag) or soluble (OVA) Ag. In both cases, coadministration of 1 microg of a soluble fusion protein between murine LAG-3 and the Fc fraction of a murine IgG2a mAb (mLAG-3Ig) as a vaccine adjuvant induced or increased CTL responses to the corresponding MHC class I-restricted peptide. In addition, splenocytes of mice vaccinated with either the particulate or soluble Ag plus mLAG-3Ig exhibited a significantly greater proliferative response than did splenocytes of mice immunized with Ag and a control Ig molecule. Similarly, these splenocytes had a greater Th1- but not Th2-type cytokine response. Finally, mice immunized with Ag plus mLAG-3Ig produced higher titers of Abs than mice immunized with Ag and a control Ig molecule. Thus, these data provide evidence of a novel means of improving the immunogenicity of subunit vaccines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / administration & dosage*
  • Adjuvants, Immunologic / genetics
  • Animals
  • Antigens, CD*
  • Cytokines / biosynthesis
  • Epitopes, T-Lymphocyte / immunology
  • Female
  • Hepatitis B Antibodies / biosynthesis
  • Hepatitis B Surface Antigens / administration & dosage
  • Hepatitis B Surface Antigens / immunology*
  • Immunoglobulin Fc Fragments / administration & dosage
  • Immunoglobulin Fc Fragments / genetics
  • Immunoglobulin G / biosynthesis
  • Injections, Subcutaneous
  • Lymphocyte Activation Gene 3 Protein
  • Lymphocyte Activation*
  • Membrane Proteins / administration & dosage
  • Membrane Proteins / genetics
  • Membrane Proteins / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Ovalbumin / administration & dosage
  • Ovalbumin / immunology*
  • Recombinant Fusion Proteins / administration & dosage
  • Recombinant Fusion Proteins / immunology
  • Solubility
  • T-Lymphocytes, Cytotoxic / immunology
  • Th1 Cells / immunology
  • Th1 Cells / metabolism
  • Th2 Cells / immunology
  • Th2 Cells / metabolism
  • Vaccines / administration & dosage
  • Vaccines / genetics
  • Vaccines / immunology*


  • Adjuvants, Immunologic
  • Antigens, CD
  • Cytokines
  • Epitopes, T-Lymphocyte
  • Hepatitis B Antibodies
  • Hepatitis B Surface Antigens
  • Immunoglobulin Fc Fragments
  • Immunoglobulin G
  • Membrane Proteins
  • Recombinant Fusion Proteins
  • Vaccines
  • Ovalbumin
  • Lymphocyte Activation Gene 3 Protein
  • Lag3 protein, mouse