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Intranasal Vaccination Using Interleukin-12 and Cholera Toxin Subunit B as Adjuvants To Enhance Mucosal and Systemic Immunity to Human Immunodeficiency Virus Type 1 Glycoproteins

Diana I. Albu,¹ Agnes Jones-Trower,^2, Amy M. Woron,^1, Kathleen Stellrecht,¹ Christopher C. Broder,² and Dennis W. Metzger^1*

Center for Immunology and Microbial Disease, Albany Medical College, Albany, New York 12208 ,¹ Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814²

Received 7 November 2002/ Accepted 18 February 2003

We have investigated the induction of protective mucosal immunity to human immunodeficiency virus type 1 (HIV-1) isolate 89.6 by intranasal (i.n.) immunization of mice with gp120 and gp140 together with interleukin-12 (IL-12) and cholera toxin subunit B (CTB) as adjuvants. It was found that both IL-12 and CTB were required to elicit mucosal antibody responses and that i.n. immunization resulted in increased total, immunoglobulin G1 (IgG1), and IgG2a anti-HIV-1 antibody levels in serum; increased total, IgG1, IgG2a, and IgA antibody expression in bronchoalveolar lavage fluids; and increased IgA antibody levels in vaginal washes. Levels of anti-HIV-1 antibodies in both sera and secretions were higher in groups immunized with gp140 than in those immunized with gp120. However, only gp120-specific mucosal antibodies demonstrated neutralizing activity against HIV-1 89.6. Taken together, the results show that IL-12 and CTB act synergistically to enhance both systemic and local mucosal antibody responses to HIV-1 glycoproteins and that even though gp140 induces higher antibody titers than gp120, only gp120-specific mucosal antibodies interfere with virus infectivity.

Present address: Division of Viral Products, CBER/FDA, Rockville, MD 20852.

Present address: New York State Department of Health, Wadsworth Center, DID/DAI/BD, Albany, NY 12208.

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