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Journal of Virology, January 2002, p. 517-524, Vol. 76, No. 2
0022-538X/01/$04.00+0     DOI: 10.1128/JVI.76.2.517-524.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

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

Curtis P. Bradney,1 Gregory D. Sempowski,1,2,3 Hua-Xin Liao,1,2,3 Barton F. Haynes,1,2,3 and Herman F. Staats1,2,3,4,5*

Departments of Medicine,1 Human Vaccine Institute,2 Center For AIDS Research, Duke University Medical Center, Durham, North Carolina 27710,3 Immunology,4 Pathology5

Received 13 June 2001/ Accepted 9 October 2001

Safe and potent new adjuvants are needed for vaccines that are administered to mucosal surfaces. This study was performed to determine if interleukin-1{alpha} (IL-1{alpha}) 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-1{alpha}, 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-1{alpha}, 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-1{alpha}, 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.

* Corresponding author. Mailing address: Box 3307, Department of Medicine, Duke University Medical Center, Durham, NC 27710. Phone: (919) 684-8824. Fax: (919) 684-4288. E-mail: hfs{at}acpub.duke.edu.

Journal of Virology, January 2002, p. 517-524, Vol. 76, No. 2
0022-538X/01/$04.00+0     DOI: 10.1128/JVI.76.2.517-524.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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