CD8+ T-cell-mediated cross-clade protection in the genital tract following intranasal immunization with inactivated human immunodeficiency virus antigen plus CpG oligodeoxynucleotides
| Autor: | Amy J. Patrick, Kenneth L. Rosenthal, Janina Q. Jiang, Ronald B. Moss |
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| Rok vydání: | 2004 |
| Předmět: |
CpG Oligodeoxynucleotide
HIV Antigens medicine.medical_treatment Immunology HIV Infections Biology CD8-Positive T-Lymphocytes HIV Envelope Protein gp120 Microbiology Virus Mice Immune system Antigen Adjuvants Immunologic Virology Vaccines and Antiviral Agents medicine Cytotoxic T cell Animals Humans Immunity Mucosal Administration Intranasal AIDS Vaccines Genitalia Female Mice Inbred C57BL Administration Intravaginal Immunization Oligodeoxyribonucleotides Vaccines Inactivated Insect Science HIV-1 Female Adjuvant |
| Zdroj: | Journal of virology. 79(1) |
| ISSN: | 0022-538X |
| Popis: | 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-γ) and β-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-1gagfrom 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. |
| Databáze: | OpenAIRE |
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