Robust genital gag-specific CD8+ T-cell responses in mice upon intramuscular immunization with simian adenoviral vectors expressing HIV-1-gag.
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.
Wistar Institute, Philadelphia, PA 19104, USA.
Larissa H
LH
Haut
Shih W
SW
Lin
Nia
N
Tatsis
Lauren J
LJ
DiMenna
Wynetta
W
Giles-Davis
Aguinaldo R
AR
Pinto
Hildegund C J
HC
Ertl
D000261:Adenoviruses, Simian / Q000235:genetics*; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D004333:Drug Administration Routes; D005260:Female; D005822:Genetic Vectors / Q000008:administration & dosage; D005835:Genitalia / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D015497:HIV-1 / Q000276:immunology*; D007114:Immunization; D007156:Immunologic Memory / Q000187:drug effects; D007371:Interferon-gamma / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D002679:Pan troglodytes; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
D054301:gag Gene Products, Human Immunodeficiency Virus; D007371:Interferon-gamma