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Journal of Virology, January 2005, p. 393-400, Vol. 79, No. 1
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.1.393-400.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

CD8+ T-Cell-Mediated Cross-Clade Protection in the Genital Tract following Intranasal Immunization with Inactivated Human Immunodeficiency Virus Antigen Plus CpG Oligodeoxynucleotides

Janina Q. Jiang,1 Amy Patrick,1 Ronald B. Moss,2 and Kenneth L. Rosenthal1*

Centre for Gene Therapeutics, Department of Pathology and Molecular Medicine, McMaster University Health Sciences Center, Hamilton, Ontario, Canada,1 and The Immune Response Corporation, Carlsbad, California2

Received 18 March 2004/ Accepted 23 August 2004

Human immunodeficiency virus (HIV) is a mucosally transmitted infection that rapidly targets and depletes CD4+ T cells in mucosal tissues and establishes a major reservoir for viral persistence in gut-associated lymphoid tissues. Therefore, vaccines designed to prevent HIV infections must induce potent and durable mucosal immune responses, especially in the genital tract. Here we investigated whether intranasal (i.n.) immunization with inactivated gp120-depleted HIV-1 antigen (Ag) plus CpG oligodeoxynucleotide (ODN) as an adjuvant induced local immune responses in the genital tract and cross-clade protection against intravaginal (IVAG) challenge. Lymphocytes isolated from the iliac lymph nodes (ILNs) and genital tracts of female mice i.n. immunized with HIV-1 Ag plus CpG showed significant HIV-specific proliferation and produced significantly higher levels of gamma interferon (IFN-{gamma}) and ß-chemokines than mice immunized with HIV-1 Ag alone or mixed with non-CpG ODN. CD8+ lymphocytes were dramatically increased in the genital tracts of mice immunized with HIV-1 Ag plus CpG, and protection following IVAG challenge with recombinant vaccinia viruses (rVVs) expressing HIV-1 gag was shown to be CD8 dependent. Finally, cross-clade protection was observed between clades A, C, and G but not B following IVAG challenge with rVVs expressing HIV-1 gag from different clades. These studies provide evidence that mucosal (i.n.) immunization induced strong local T-cell-mediated immune responses in the genital tract and cross-clade protection against IVAG challenge.

* Corresponding author. Mailing address: Department of Pathology & Molecular Medicine, McMaster University, MDCL 4019, 1200 Main St. West, Hamilton, Ontario, Canada L8N 3Z5. Phone: (905) 525-9140, ext. 22375. Fax: (905) 522-6750. E-mail: rosenthl{at}mcmaster.ca.

Journal of Virology, January 2005, p. 393-400, Vol. 79, No. 1
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.1.393-400.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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Copyright © 2005 by the American Society for Microbiology. All rights reserved.