Induction of protection against tetanus toxin in mice by tetanus toxoid-liposome conjugate.
Tetanus toxoid (Ttd) was coupled to liposomes via glutaraldehyde. Intraperitoneal injection in BALB/c mice with Ttd-liposomes induced a substantial amount of anti-Ttd IgG antibody production and an extremely low level of anti-Ttd IgE antibody production. Mice immunized with Ttd-liposomes were successfully protected against a subsequent challenge with a lethal dose of tetanus toxin (Ttx). On the other hand, aluminum hydroxide-adsorbed Ttd (Ttd-alum) and plain Ttd solution induced the production of both IgG and IgE antibodies against Ttd. Moreover, secondary immunization with Ttd-liposomes in mice, in which anti-Ttd IgE antibody production was induced by Ttd-alum led to enhanced anti-Ttd IgG and a limited anti-Ttd IgE antibody production. When Ttd-liposome preparation was lyophilized, the efficacy of Ttd-liposomes was maintained for 6 months at 37 C, suggesting that this vaccine preparation would be stable without refrigeration. These results demonstrate the potential ability of Ttd-liposome conjugates to produce a tetanus vaccine which provides protection against (Ttx) while inducing the least amount of anti-Ttd IgE antibodies.
Department of Safety Research on Biologics, National Institute of Infectious Diseases, Tokyo, Japan.
S
S
Naito
A
A
Horino
T
T
Komiya
T
T
Fukuda
M
M
Takahashi
Y
Y
Ami
Y
Y
Suzaki
T
T
Oka
K
K
Okuma
M
M
Morokuma
Y
Y
Nakano
M
M
Mori
S
S
Nishinohara
K
K
Komuro
T
T
Uchida
D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D005260:Female; D008081:Liposomes; D051379:Mice; D008807:Mice, Inbred BALB C; D013742:Tetanus / Q000276:immunology / Q000517:prevention & control*; D013744:Tetanus Toxin / Q000276:immunology*; D013745:Tetanus Toxoid / Q000008:administration & dosage* / Q000276:immunology
D000907:Antibodies, Bacterial; D008081:Liposomes; D013744:Tetanus Toxin; D013745:Tetanus Toxoid