Gender Differences in Human Immunodeficiency Virus Type 1-Specific CD8 Responses in the Reproductive Tract and Colon following Nasal Peptide Priming and Modified Vaccinia Virus Ankara Boosting
AUTOR(ES)
Peacock, James W.
FONTE
American Society for Microbiology
RESUMO
Induction of mucosal anti-human immunodeficiency virus type 1 (HIV-1) T-cell responses in males and females will be important for the development of a successful HIV-1 vaccine. An HIV-1 envelope peptide, DNA plasmid, and recombinant modified vaccinia virus Ankara (rMVA) expressing the H-2Dd-restricted cytotoxic T lymphocyte P18 epitope were used as immunogens to test for their ability to prime and boost anti-HIV-1 T-cell responses at mucosal and systemic sites in BALB/c mice. We found of all prime-boost combinations tested, an HIV-1 Env peptide subunit mucosal prime followed by systemic (intradermal) boosting with rMVA yielded the maximal induction of gamma interferon (IFN-γ) spot-forming cells in the female genital tract and colon. However, this mucosal prime-systemic rMVA boost regimen was minimally immunogenic for the induction of genital, colon, or lung anti-HIV-1 T-cell responses in male mice. We determined that a mucosal Env subunit immunization could optimally prime an rMVA boost in female but not male mice, as determined by the magnitude of antigen-specific IFN-γ responses in the reproductive tracts, colon, and lung. Defective mucosal priming in male mice could not be overcome by multiple mucosal immunizations. However, rMVA priming followed by an rMVA boost was the optimal prime-boost strategy for male mice as determined by the magnitude of antigen-specific IFN-γ responses in the reproductive tract and lung. Thus, prime-boost immunization strategies able to induce mucosal antigen-specific IFN-γ responses were identified for male and female mice. Understanding the cellular and molecular basis of gender-determined immune responses will be important for optimizing induction of anti-HIV-1 mucosal immune responses in both males and females.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=524967Documentos Relacionados
- Comprehensive Screening Reveals Strong and Broadly Directed Human Immunodeficiency Virus Type 1-Specific CD8 Responses in Perinatally Infected Children
- Ontogeny and Specificities of Mucosal and Blood Human Immunodeficiency Virus Type 1-Specific CD8+ Cytotoxic T Lymphocytes
- Residual Viral Replication during Antiretroviral Therapy Boosts Human Immunodeficiency Virus Type 1-Specific CD8+ T-Cell Responses in Subjects Treated Early after Infection
- Trafficking of Human Immunodeficiency Virus Type 1-Specific CD8+ T Cells to Gut-Associated Lymphoid Tissue during Chronic Infection
- Consistent Patterns in the Development and Immunodominance of Human Immunodeficiency Virus Type 1 (HIV-1)-Specific CD8+ T-Cell Responses following Acute HIV-1 Infection