Robust genital gag‐specific CD8⁺ T‐cell responses in mice upon intramuscular immunization with simian adenoviral vectors expressing HIV‐1‐gag

• Published in: European journal of immunology 2010-12, Vol.40 (12), p.3426-3438
• Main Authors: Haut, Larissa H, Lin, Shih W, Tatsis, Nia, DiMenna, Lauren J, Giles‐Davis, Wynetta, Pinto, Aguinaldo R, Ertl, Hildegund C.J
• Format: Article
• Language: English
• Subjects: Adenovirus; Adenoviruses; Adenoviruses, Simian - genetics; Animals; CD8-Positive T-Lymphocytes - drug effects; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; CD8-Positive T-Lymphocytes - pathology; Cells, Cultured; Drug Administration Routes; Female; gag Gene Products, Human Immunodeficiency Virus - administration & dosage; gag Gene Products, Human Immunodeficiency Virus - genetics; gag Gene Products, Human Immunodeficiency Virus - immunology; gag Gene Products, Human Immunodeficiency Virus - metabolism; Genetic Vectors - administration & dosage; Genitalia - drug effects; Genitalia - immunology; Genitalia - metabolism; Genitalia - pathology; HIV; HIV-1 - immunology; Immunization; Immunologic Memory - drug effects; Interferon-gamma - secretion; Lymphocyte Activation - drug effects; Mice; Mice, Inbred BALB C; Mucosal; Pan troglodytes; T cell receptors; T cells; Vaccines
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.201040440

Most studies on E1‐deleted adenovirus (Ad) vectors as vaccine carriers for antigens of HIV‐1 have focused on induction of central immune responses, although stimulation of mucosal immunity at the genital tract (GT), the primary port of entry of HIV‐1, would also be highly desirable. In this study, different immunization protocols using chimpanzee‐derived adenoviral (AdC) vectors expressing Gag of HIV‐1 clade B given in heterologous prime‐boost regimens were tested for induction of systemic and genital immune responses. Although i.n. immunization stimulated CD8⁺ T‐cell responses that could be detected in the GT, this route induced only marginal cellular responses in systemic tissues and furthermore numbers of Gag‐specific CD8⁺ T cells contracted sharply within a few weeks. On the contrary, i.m. immunization induced higher and more sustained frequencies of vaccine‐induced cells which could be detected in the GT as well as systemic compartments. Antigen‐specific CD8⁺ T cells could be detected 1 year after immunization in all compartments analyzed. Genital memory cells secreted IFN‐γ, expressed high levels of CD103 and their phenotypes were consistent with a state of activation. Taken together, the results presented here show that i.m. vaccination with chimpanzee‐derived (simian) adenovirus vectors is a suitable strategy to induce a long‐lived genital CD8⁺ T‐cell response.