TY - JOUR
T1 - Immune consequences of intraocular administration of modified adenoviral vectors
AU - Suber, M. L.
AU - Hurwitz, M. Y.
AU - Chévez-Barrios, Patricia
AU - Hurwitz, Richard
PY - 2001/8/9
Y1 - 2001/8/9
N2 - To investigate the immune consequences of intraocular administration of modified adenoviral vectors, C57BL/6 normal and retinal degeneration C57BL/6 (rd/rd) mice were immunized with subcutaneous, sub-retinal, vitreal, or anterior chamber injections of replication-deficient adenovirus (AdV) containing the Escherichia coli β-galactosidase gene (AdV-LacZ). Fourteen days after the initial inoculation, the animals were immune challenged with an injection of AdV-LacZ in the right ear pinna. Antigen-induced delayed type hypersensitivity (DTH) was measured by determining relative ear swelling. Normal C57BL/6 mice immunized with subretinal, vitreal, or anterior chamber injections did not demonstrate a DTH response. The rd/rd C57BL/6 mice injected in the anterior chamber with the viral construct also did not respond with DTH in a manner similar to normal mice responding to intraocular injection and subsequent challenge. However, the rd/rd C57BL/6 mice immunized by the subretinal or vitreal route did respond to immune challenge with a DTH response. Histologic examination of the eyes showed a lack of infiltration by inflammatory cells. Although these results suggest that the potential for immune consequences is reduced when modified adenoviral vectors are used in the normal ocular environment, these vectors used in the vitreal cavity of rd/rd animals may induce a systemic response to the vectors.
AB - To investigate the immune consequences of intraocular administration of modified adenoviral vectors, C57BL/6 normal and retinal degeneration C57BL/6 (rd/rd) mice were immunized with subcutaneous, sub-retinal, vitreal, or anterior chamber injections of replication-deficient adenovirus (AdV) containing the Escherichia coli β-galactosidase gene (AdV-LacZ). Fourteen days after the initial inoculation, the animals were immune challenged with an injection of AdV-LacZ in the right ear pinna. Antigen-induced delayed type hypersensitivity (DTH) was measured by determining relative ear swelling. Normal C57BL/6 mice immunized with subretinal, vitreal, or anterior chamber injections did not demonstrate a DTH response. The rd/rd C57BL/6 mice injected in the anterior chamber with the viral construct also did not respond with DTH in a manner similar to normal mice responding to intraocular injection and subsequent challenge. However, the rd/rd C57BL/6 mice immunized by the subretinal or vitreal route did respond to immune challenge with a DTH response. Histologic examination of the eyes showed a lack of infiltration by inflammatory cells. Although these results suggest that the potential for immune consequences is reduced when modified adenoviral vectors are used in the normal ocular environment, these vectors used in the vitreal cavity of rd/rd animals may induce a systemic response to the vectors.
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U2 - 10.1089/104303401750148801
DO - 10.1089/104303401750148801
M3 - Article
C2 - 11339899
AN - SCOPUS:0034922022
VL - 12
SP - 833
EP - 838
JO - Human Gene Therapy
JF - Human Gene Therapy
SN - 1043-0342
IS - 7
ER -