Protection of monkeys against Shiga toxin induced by Shiga toxin-liposome conjugates.
BACKGROUND
We previously reported that the purified Shiga toxins (Stx) Stx1 and Stx2, when coupled with liposomes, induced substantial production of anti-Stx1 and anti-Stx2 IgG antibody, respectively, in mice. The levels of anti-Stx antibody in the sera of mice immune to Stx-liposome correlated well with the protection against subsequent challenge with Stx. Furthermore, mice immunized with a mixture of Stx1-liposome and Stx2-liposome were successfully protected against oral infection with cytotoxin-producing Escherichia coli O157:H7.


METHODS
In this study, the induction of protection against Stx2 by Stx2-liposomes was evaluated in monkeys.


RESULTS
Stx2-liposomes induced a substantial amount of anti-Stx2 IgG antibodies as well as Stx2 neutralizing antibodies in monkeys. Test monkeys were successfully protected against challenge with lethal doses of Stx2. Moreover, these monkeys showed no apparent symptoms, while nonimmunized control monkeys died within 4 days with hemorrhagic gastroenteritis and renal disorder. In addition, as shown by other cases involving antigen-liposome conjugates, Stx2-liposome did not induce anti-Stx2 IgE antibody production, though it stimulated the production of a substantial amount of anti-Stx2 IgG antibodies.


CONCLUSIONS
These results suggest that Stx-liposome conjugates may serve as candidate vaccines to induce protection against death caused by cytotoxin-producing E. coli infection.
Suzaki
Yuriko
Y
Division of Experimental Animals Research, Department of Safety Research on Biologics, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashimurayama, Tokyo 208-0011, Japan.
Ami
Yasushi
Y
Nagata
Noriyo
N
Naito
Seishiro
S
Kato
Hiroshi
H
Taneichi
Maiko
M
Takahashi
Motohide
M
Komiya
Takako
T
Satoh
Sachihiro
S
Gondaira
Fumio
F
Sugiyama
Junichi
J
Nakano
Yoshio
Y
Mori
Masahito
M
Komuro
Katsutoshi
K
Uchida
Tetsuya
T
D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis / Q000097:blood; D003092:Colitis / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology / Q000517:prevention & control; D004927:Escherichia coli Infections / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology / Q000517:prevention & control; D006651:Histocytochemistry; D007114:Immunization; D007422:Intestines / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D008081:Liposomes; D008252:Macaca fascicularis; D022641:Shiga Toxin 2 / Q000008:administration & dosage / Q000096:biosynthesis / Q000276:immunology*
D000907:Antibodies, Bacterial; D008081:Liposomes; D022641:Shiga Toxin 2