Intramuscular rather than oral administration of replication-defective adenoviral vaccine vector induces specific CD8+ T cell responses in the gut.
Gut-associated lymphoid tissue (GALT) is the primary replication site for HIV-1, resulting in a pronounced CD4(+) T cell loss in this tissue during primary infection. A mucosal vaccine that generates HIV-specific CD8(+) T cells in the gut could prevent the establishment of founder populations and broadcasting of virus. Here, we immunized mice orally and systemically with a chimpanzee derived adenoviral vector expressing HIV gag (AdC68gag) and measured frequencies of gag-specific interferon-gamma (IFN-gamma) producing CD8(+) T cells in the GALT. A single oral administration was inefficient at eliciting responses in the mesenteric lymph nodes and Peyer's Patches, while a single intramuscular administration elicited strong systemic and detectable mucosal responses. The gag-specific CD8(+) T cell responses were present in both acute and memory phases following intramuscular administration.
Lin
S W
SW
School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Cun
A S
AS
Harris-McCoy
K
K
Ertl
H C
HC
D000256:Adenoviridae / Q000235:genetics; D000284:Administration, Oral; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D003673:Defective Viruses / Q000235:genetics / Q000276:immunology; D005434:Flow Cytometry; D015683:Gene Products, gag / Q000235:genetics / Q000276:immunology; D005822:Genetic Vectors / Q000008:administration & dosage; D006678:HIV / Q000235:genetics; D018928:Immunity, Mucosal / Q000276:immunology; D007273:Injections, Intramuscular; D007371:Interferon-gamma / Q000378:metabolism; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D014765:Viral Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D014779:Virus Replication / Q000235:genetics
D015683:Gene Products, gag; D014765:Viral Vaccines; D007371:Interferon-gamma