Recombinant interleukin 2 as an adjuvant for vaccine-induced protection. Immunization of guinea pigs with herpes simplex virus subunit vaccines.
We determined that recombinant interleukin 2 (rIL-2) administered in conjunction with herpes simplex virus (HSV) crude extract or recombinant glycoprotein D subunit vaccine enhances the protective effect of either antigen preparation against HSV type 2 genital infection in guinea pigs. Animals that received the vaccine accompanied by rIL-2 had an incidence of infection, assessed by detection of clinical lesions and/or viral shedding, that varied between 0 and 43% significantly lower than the incidence of 63 to 100% in guinea pigs submitted to the same immunization schedule without rIL-2. Animals that escaped acute infection failed to develop recurrent disease. In addition, severity of acute infection was decreased by rIL-2 co-administration as well as by increasing the number of vaccine doses. We also studied the immune response of the guinea pigs to vaccination and the mechanism of protection. Both enzyme-linked immunosorbent assay titers of antibodies to HSV type 2 and specific antigen stimulation of lymphocytes measured by proliferation and interferon production did not significantly differ among the immunization groups. However, specific cellular cytotoxicity was enhanced by rIL-2 co-administration and was positively correlated with protection. This suggests that rIL-2 may become an important adjuvant in active immunization programs using subunit vaccines, particularly against diseases in which cellular cytotoxicity is a major defense mechanism.
Weinberg
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Department of Medicine, Stanford University School of Medicine, CA 94305.
Merigan
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TC
D000276:Adjuvants, Immunologic; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis*; D003602:Cytotoxicity, Immunologic; D005260:Female; D005831:Genital Diseases, Female / Q000517:prevention & control; D006168:Guinea Pigs; D006561:Herpes Simplex / Q000517:prevention & control*; D007111:Immunity, Cellular; D007376:Interleukin-2 / Q000276:immunology*; D011994:Recombinant Proteins / Q000627:therapeutic use; D018139:Simplexvirus / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D007376:Interleukin-2; D011994:Recombinant Proteins; D014765:Viral Vaccines