Effect of MTP-PE liposomes and interleukin-7 on induction of antibody and cell-mediated immune responses to a recombinant HIV-envelope protein.
We investigated the ability of human recombinant interleukin-7 (IL-7) to enhance the immune responses of mice vaccinated with either the alum-associated or liposome-formulated recombinant human immunodeficiency virus (HIV)-envelope protein, env-2-3SF2 (a nonglycosylated denatured gp 120 of HIV-1SF2 produced in genetically engineered yeast). Pathogen-free (C3H) mice were vaccinated on days 0, 14, and 28 with 10 micrograms of either the alum-associated env-2-3SF2 or liposome-formulated env-2-3SF2, both containing a lipophylic muramyl tripeptide, MTP-PE. Liposome-formulated IL-7 (5 micrograms/mouse) or empty liposomes were given on days 7, 14, 21, and 28. Antibody response against the immunized antigen, evaluated on day 21 and day 35 or 42, showed that liposome-formulated antigen induced higher antibody titer than did alum-associated antigen, and these antibody responses can be enhanced by concurrent administration of IL-7 liposomes. Spleen cells were harvested on day 21 and day 35 or 42 to evaluate cytotoxic T lymphocyte responses directed against autologous cells infected with vaccinia virus-expressing HIV-envelope protein. Mice treated with liposome-formulated antigen expressed the highest cytotoxic t-lymphocyte (CTL) activity, regardless of whether IL-7 liposome was given as an immune potentiator. In contrast, spleen cells from mice vaccinated with alum-associated antigen exhibited minimal CTL response, which was enhanced by concurrent IL-7 liposome treatment. Collectively, IL-7 liposome treatment enhanced the antibody production of the alum-associated or liposome-formulated env-2-3SF2, whereas its enhancement of CTL activity was detected only in mice vaccinated with alum-associated antigen.
Department of Pharmaceutics, University of Washington, Seattle 98195.
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Bui
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Dykers
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Faltynek
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D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000276:immunology; D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D003602:Cytotoxicity, Immunologic; D004337:Drug Carriers; D015686:Gene Products, env / Q000276:immunology*; D015483:HIV Antibodies / Q000096:biosynthesis; D015497:HIV-1 / Q000276:immunology*; D015851:Interleukin-7 / Q000008:administration & dosage / Q000276:immunology*; D008081:Liposomes; D051379:Mice; D008809:Mice, Inbred C3H; D010714:Phosphatidylethanolamines / Q000008:administration & dosage / Q000276:immunology*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology; D013047:Specific Pathogen-Free Organisms; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology
D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D004337:Drug Carriers; D015686:Gene Products, env; D015483:HIV Antibodies; D015851:Interleukin-7; D008081:Liposomes; D010714:Phosphatidylethanolamines; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic; C037144:mifamurtide; D000119:Acetylmuramyl-Alanyl-Isoglutamine