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Journal of Virology, September 2003, p. 9823-9830, Vol. 77, No. 18
0022-538X/03/$08.00+0 DOI: 10.1128/JVI.77.18.9823-9830.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia 30322,1 Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas 770302
Received 6 March 2003/ Accepted 16 June 2003
To enhance the efficiency of antigen uptake at mucosal surfaces, CTB was conjugated to simian immunodeficiency virus (SIV) virus-like particles (VLPs). We characterized the immune responses to the Env and Gag proteins after intranasal administration. Intranasal immunization with a mixture of VLPs and CTB as an adjuvant elicited higher levels of SIV gp160-specific immunoglobulin G (IgG) in sera and IgA in mucosae, including saliva, vaginal-wash samples, lung, and intestine, as well as a higher level of neutralization activities than immunization with VLPs alone. Conjugation of CTB to VLPs also enhanced the SIV VLP-specific antibodies in sera and in mucosae to similar levels. Interestingly, CTB-conjugated VLPs showed higher levels of cytokine (gamma interferon)-producing splenocytes and cytotoxic-T-lymphocyte activities of immune cells than VLPs plus CTB, as well as an increased level of both IgG1 and IgG2a serum antibodies, which indicates enhancement of both Th1- and Th2-type cellular immune responses. These results demonstrate that CTB can be an effective mucosal adjuvant in the context of VLPs to induce enhanced humoral, as well as cellular, immune responses.
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