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Journal of Virology, May 2003, p. 5589-5597, Vol. 77, No. 10
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.10.5589-5597.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

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,{dagger} Amy M. Woron,1,{ddagger} Kathleen Stellrecht,1 Christopher C. Broder,2 and Dennis W. Metzger1*

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.

* Corresponding author. Mailing address: Center for Immunology and Microbial Disease, MC 151, Albany Medical College, 47 New Scotland Ave., Albany, NY 12208. Phone: (518) 262-6026. Fax: (518) 262-6053. E-mail: metzged{at}mail.amc.edu.

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

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

Journal of Virology, May 2003, p. 5589-5597, Vol. 77, No. 10
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.10.5589-5597.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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