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 a djuvants but often lack the potency of other, more reactogenic compounds. O n the basis of the observation that attachment of IFN-gamma to antigen coul d further enhance its adjuvanticity, a chimeric protein involving IFN-gamma and gp120 of human immunodeficiency virus was produced, using varying leng ths of amino acid linkers between the two moieties. All resultant fusion pr oteins 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, particul arly of the IgG2a subclass. In addition, both T cell proliferation and IFN- gamma production in response to antigen were strongly enhanced by primary i mmunization with the fusion protein. IFN-gamma fused to antigen is a more p otent adjuvant for Th1-like responses than is IFN-gamma mixed with antigen.