Encapsulation of recombinant adenovirus into alginate microspheres circumvents vector-specific immune response.
Pre-existing immunity against adenoviruses may compromise the efficacy of adenoviral vectors for vaccination and gene therapy. The purpose of this study was to determine whether encapsulation of adenovirus recombinants into biodegradable alginate microparticles could circumvent the vector-specific immune response. Mice were immunized either intranasally (i.n.) or intraperitoneally (i.p.) with human adenovirus type 5 (HAd5), resulting in the development of virus-specific antibodies. Immunized and nai;ve mice were inoculated with AdCA36lacZ (an E1-deleted HAd5 recombinant containing the bacterial beta-galactosidase (LacZ) gene), encapsulated (E) into alginate microparticles, or nonencapsulated (NE) ie, as a virus suspension. LacZ expression in animals immunized once (1x) or twice (2x) with HAd5 and subsequently inoculated with NE-AdCA36lacZ (NE-Z) was significantly (P<0.001) reduced compared to those levels observed in NE-Z inoculated nai;ve mice, suggesting that the immune response against the vector adversely affected transgene expression. In contrast, there was only slight reduction (P>0.05) in LacZ expression in mice immunized 1x or 2x with HAd5 that were subsequently inoculated with E-AdCA36lacZ (E-Z) compared to those levels obtained in E-Z inoculated nai;ve animals. Similar results were obtained with i.n. or i.p. inoculated animals. These results indicate that microencapsulation of recombinant adenovirus effectively circumvented the vector-specific immune response.
Sailaja
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G
Department of Veterinary Pathobiology, School of Veterinary Medicine, Purdue University, West Lafayette, IN 47907, USA.
HogenEsch
H
H
North
A
A
Hays
J
J
Mittal
S K
SK
D000256:Adenoviridae / Q000235:genetics*; D000281:Administration, Intranasal; D000464:Alginates; D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis; D001672:Biocompatible Materials; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D015870:Gene Expression; D005818:Genetic Engineering; D005822:Genetic Vectors; D020723:Glucuronic Acid; D006603:Hexuronic Acids; D007070:Immunoglobulin A / Q000032:analysis; D007074:Immunoglobulin G / Q000032:analysis; D007274:Injections, Intraperitoneal; D007668:Kidney / Q000378:metabolism; D007763:Lac Operon; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008198:Lymph Nodes / Q000378:metabolism; D008643:Mesentery / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008863:Microspheres; D010537:Peritoneum / Q000378:metabolism; D013154:Spleen / Q000378:metabolism; D014132:Trachea / Q000378:metabolism
D000464:Alginates; D000914:Antibodies, Viral; D001672:Biocompatible Materials; D006603:Hexuronic Acids; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D020723:Glucuronic Acid