Multiple immunizations with adenovirus and MVA vectors improve CD8+ T cell functionality and mucosal homing.
Recombinant adenovirus vectors and MVA vectors were used in prime boost vaccine regimens to address the impact of repeated immunizations on transgene product-specific CD8(+) T cell frequencies, phenotypes, function, and localization. We show that a regimen with three immunizations incorporating MVA, human adenovirus serotype 5 and chimpanzee-derived adenoviruses serotype 68 or 7 yields high transgene product-specific CD8(+) T cell frequencies in spleen, blood, lymph nodes, and peritoneal lavage. Furthermore, upon triple immunization increased frequencies of transgene-specific T cells were measured at mucosal sites such as mesenteric lymph nodes, intestinal epithelium, and Peyer's patches. Multiple dose vaccine regimens that markedly increase functionally active transgene-specific T cells and target them to the appropriate ports of entry may be important in protection against pathogens such as HIV-1.
Tatsis
Nia
N
The Wistar Institute, Philadelphia, PA, USA. tatsis@wistar.org
Lin
Shih-Wen
SW
Harris-McCoy
Kimberly
K
Garber
David A
DA
Feinberg
Mark B
MB
Ertl
Hildegund C J
HC
D016915:AIDS Vaccines / Q000008:administration & dosage* / Q000235:genetics; D000256:Adenoviridae / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D015683:Gene Products, gag / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D005822:Genetic Vectors; D015497:HIV-1 / Q000235:genetics / Q000276:immunology; D006801:Humans; D007114:Immunization; D007115:Immunization Schedule; D007117:Immunization, Secondary; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology*; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D010581:Peyer's Patches / Q000166:cytology / Q000276:immunology; D014616:Vaccinia virus / Q000235:genetics* / Q000378:metabolism
D016915:AIDS Vaccines; D015683:Gene Products, gag