Affiliation:
1. Departments of Medicine
2. Human Vaccine Institute
3. Center For AIDS Research, Duke University Medical Center, Durham, North Carolina 27710
4. Immunology
5. Pathology
Abstract
ABSTRACT
Safe and potent new adjuvants are needed for vaccines that are administered to mucosal surfaces. This study was performed to determine if interleukin-1α (IL-1α) 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 μg of an HIV
env
peptide immunogen with IL-1α, 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-1α, 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-1α, 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.
Publisher
American Society for Microbiology
Subject
Virology,Insect Science,Immunology,Microbiology
Reference54 articles.
1. Ahlers, J. D., N. Dunlop, D. W. Alling, P. L. Nara, and J. A. Berzofsky. 1997. Cytokine-in-adjuvant steering of the immune response phenotype to Hiv-1 vaccine constructs — granulocyte-macrophage colony-stimulating factor and Tnf-alpha synergize with Il-12 to enhance induction of cytotoxic T lymphocytes. J. Immunol. 158 : 3947–3958.
2. Anonymous. 2000. AIDS epidemic update: December 2000. Joint United Nations Programme on HIV/AIDS (UNAIDS). UNAIDS Geneva Switzerland.
3. Anonymous. 2000. Report on the global HIV/AIDS epidemic. Joint United Nations Programme on HIV/AIDS Geneva Switzerland.
4. Monoclonal immunoglobulin A antibodies directed against cholera toxin prevent the toxin-induced chloride secretory response and block toxin binding to intestinal epithelial cells in vitro
5. Atkins, M. B., M. J. Robertson, M. Gordon, M. T. Lotze, M. DeCoste, J. S. DuBois, J. Ritz, A. B. Sandler, H. D. Edington, P. D. Garzone, J. W. Mier, C. M. Canning, L. Battiato, H. Tahara, and M. L. Sherman. 1997. Phase I evaluation of intravenous recombinant human interleukin 12 in patients with advanced malignancies. Clin. Cancer Res. 3 : 409–417.
Cited by
86 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献