Immunization with an interferon-gamma-gp120 fusion protein induces enhanced immune responses to human immunodeficiency virus gp120.
Cytokines, including interferon (IFN)-gamma, can be effective immunologic adjuvants but often lack the potency of other, more reactogenic compounds. On the basis of the observation that attachment of IFN-gamma to antigen could further enhance its adjuvanticity, a chimeric protein involving IFN-gamma and gp120 of human immunodeficiency virus was produced, using varying lengths of amino acid linkers between the two moieties. All resultant fusion proteins appeared to be dimerized, but full IFN-gamma biological activity was present only with the longest, 34-aa linker. Immunization with the fusion protein gave rise to enhanced primary antibody responses to gp120, particularly of the IgG2a subclass. In addition, both T cell proliferation and IFN-gamma production in response to antigen were strongly enhanced by primary immunization with the fusion protein. IFN-gamma fused to antigen is a more potent adjuvant for Th1-like responses than is IFN-gamma mixed with antigen.
McCormick
A L
AL
Division of Genomic Medicine, University of Sheffield Medical School, Sheffield, United Kingdom. a.l.mccormick@sheffield.ac.uk
Thomas
M S
MS
Heath
A W
AW
D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000235:genetics / Q000494:pharmacology*; D000818:Animals; D019556:COS Cells; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D015483:HIV Antibodies / Q000096:biosynthesis; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology*; D015658:HIV Infections / Q000628:therapy; D015497:HIV-1 / Q000276:immunology*; D007114:Immunization; D007371:Interferon-gamma / Q000008:administration & dosage / Q000235:genetics / Q000494:pharmacology*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology
D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D016207:Cytokines; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D011993:Recombinant Fusion Proteins; D007371:Interferon-gamma