Cationic liposome conjugation to recombinant adenoviral vector reduces viral antigenicity.
Adenoviral (Ad) vectors are commonly used in gene therapy trials because of their efficiency in gene transfer. However, their use is limited by immune responses that reduce transgene expression and decrease the efficacy of repeated vector administration. In this study, we demonstrated that conjugation of Ad vector with our novel cationic liposomes could reduce viral antigenicity in vivo. Mice subcutaneously injected with liposome-conjugated Ad vector showed a 6.5-fold reduction of anti-Ad antibodies with neutralizing activity, compared to those with unconjugated Ad vector. Interestingly, we also found that the conjugated vector is less susceptible to inactivation by neutralizing antibodies in vitro and in vivo. Our results suggest that liposome conjugation reduces viral antigenicity, shields vectors from neutralizing antibody, and may allow repeated Ad vector administration.
Natsume
A
A
Department of Neurosurgery, Nagoya University School of Medicine, 65 Tsuruimai-cho, Showa-ku, Nagoya 466-8550, Japan.
Mizuno
M
M
Ryuke
Y
Y
Yoshida
J
J
D000256:Adenoviridae / Q000235:genetics / Q000276:immunology*; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D015316:Genetic Therapy; D005822:Genetic Vectors; D006367:HeLa Cells; D006801:Humans; D008081:Liposomes / Q000008:administration & dosage*; D051379:Mice; D008810:Mice, Inbred C57BL; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D000914:Antibodies, Viral; D008081:Liposomes