title: Cytokines as adjuvants for the induction of anti-human immunodeficiency virus peptide immunoglobulin G (IgG) and IgA antibodies in serum and mucosal secretions after nasal immunization.
abstract: Safe and potent new adjuvants are needed for vaccines that are administered to mucosal surfaces. This study was performed to determine if interleukin-1alpha (IL-1alpha) combined with other proinflammatory cytokines provided mucosal adjuvant activity for induction of systemic and mucosal anti-human immunodeficiency virus (HIV) peptide antibody when intranasally administered with an HIV peptide immunogen. Nasal immunization of BALB/c mice with 10 microg of an HIV env peptide immunogen with IL-1alpha, IL-12, and IL-18 on days 0, 7, 14, and 28 induced peak serum anti-HIV peptide immunoglobulin G1 (IgG1) and IgA titers of 1:131,072 and 1:7,131, respectively (P = 0.05 versus no adjuvant). The use of cholera toxin (CT) as a mucosal adjuvant induced serum IgG1 and IgA titers of 1:32,768 and 1:776, respectively. The adjuvant combination of IL-1alpha, IL-12, and IL-18 induced anti-HIV peptide IgA titers of 1:1,176, 1:7,131, and 1:4,705 in saliva, fecal extracts and vaginal lavage, respectively. Titers induced by the use of CT as an adjuvant were 1:223, 1:1,176, and 1:675, respectively. These results indicate that the proinflammatory cytokines IL-1alpha, IL-12, and IL-18 can replace CT as a mucosal adjuvant for antibody induction and are important candidates for use as mucosal adjuvants with HIV and other vaccines.
authors.affiliation: Department of Medicine, Human Vaccine Institute, Center For AIDS Research, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: Curtis P
authors.initials: CP
authors.lastname: Bradney
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Sempowski
authors.forename: Hua-Xin
authors.initials: HX
authors.lastname: Liao
authors.forename: Barton F
authors.initials: BF
authors.lastname: Haynes
authors.forename: Herman F
authors.initials: HF
authors.lastname: Staats
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000276:Adjuvants, Immunologic; D000281:Administration, Intranasal; D000818:Animals; D005260:Female; D015686:Gene Products, env / Q000276:immunology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology; D015483:HIV Antibodies / Q000097:blood / Q000276:immunology*; D015488:HIV Antigens / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology; D018928:Immunity, Mucosal / Q000276:immunology*; D007114:Immunization; D007070:Immunoglobulin A / Q000097:blood / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007279:Injections, Subcutaneous; D007375:Interleukin-1 / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology; D020382:Interleukin-18 / Q000276:immunology; D007378:Interleukins / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010446:Peptide Fragments / Q000276:immunology; D012463:Saliva / Q000276:immunology; D022223:Vaccines, Subunit / Q000276:immunology; D014621:Vagina / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D015686:Gene Products, env; D015483:HIV Antibodies; D015488:HIV Antigens; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007375:Interleukin-1; D020382:Interleukin-18; D007378:Interleukins; D010446:Peptide Fragments; D022223:Vaccines, Subunit; D018664:Interleukin-12; D016178:Granulocyte-Macrophage Colony-Stimulating Factor