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.
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.
El Mir
S
S
Laboratoire d'Immunologie des Tumeurs, Université Paris-Sud, Chatenay Malabry, France.
Triebel
F
F
D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000235:genetics; D000818:Animals; D015703:Antigens, CD; D016207:Cytokines / Q000096:biosynthesis; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D006510:Hepatitis B Antibodies / Q000096:biosynthesis; D006514:Hepatitis B Surface Antigens / Q000008:administration & dosage / Q000276:immunology*; D007141:Immunoglobulin Fc Fragments / Q000008:administration & dosage / Q000235:genetics; D007074:Immunoglobulin G / Q000096:biosynthesis; D007279:Injections, Subcutaneous; D008213:Lymphocyte Activation; D008565:Membrane Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000276:immunology; D012995:Solubility; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D014612:Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D000093322:Lymphocyte Activation Gene 3 Protein
D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D008565:Membrane Proteins; D011993:Recombinant Fusion Proteins; D014612:Vaccines; D010047:Ovalbumin; D000093322:Lymphocyte Activation Gene 3 Protein; C000720327:Lag3 protein, mouse