Anti-tetanus toxoid antibody production and protection against lethal doses of tetanus toxin in hu-PBL-SCID mice.
BACKGROUND
In this study, severe combined immunodeficiency (SCID) mice, which permit the survival of lymphoid cells of human origin, were used to study the human anti-tetanus immune response.


METHODS
Human peripheral blood lymphocytes (hu-PBL) obtained from 88 healthy donors (aged from 18 to 62) were transplanted into SCID mice, and anti-tetanus toxoid (Ttd) antibody production and protection against lethal doses of tetanus toxin (Ttx) were investigated in the hu-PBL-SCID mice.


RESULTS
The transfer of human PBL evoked significant human anti-Ttd IgG antibody production for 37.5% of the donors. After in vivo immunization, the percentage of donors with PBL exhibiting positive anti-TtD IgG production in the mice increased to 54.5%. Mean anti-Ttd IgG levels in the sera were also significantly elevated in response to immunization. The mean IgG titer for the mice injected with PBL from donors under the age of 40 was significantly higher than that of the mice injected with PBL from donors aged 40 or older. Four weeks after the cell transfer, the mice were challenged with Ttx. The induction of protection against Ttx challenge was observed mostly in mice with PBL transferred from donors under the age of 40. In vivo immunization in SCID mice with Ttd increased the number of cases of resistance to Ttx.


CONCLUSIONS
These results suggest that hu-PBL-SCID mice might serve as a tool for predicting the protective ability against pathogens in PBL donors and also for evaluating vaccine efficacy.
Naito
S
S
Department of Safety Research on Biologics, National Institute of Infectious Diseases, Tokyo, Japan.
Okada
Y
Y
Takahashi
M
M
Kato
H
H
Taneichi
M
M
Ami
Y
Y
Suzaki
Y
Y
Oka
T
T
Okuma
K
K
Morokuma
K
K
Onodera
H
H
Inoue
M
M
Takahashi
Y
Y
Yamazaki
S
S
Kimura
H
H
Komuro
K
K
Uchida
T
T
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000818:Animals; D000907:Antibodies, Bacterial / Q000032:analysis / Q000276:immunology; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis; D007928:Lethal Dose 50; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D008875:Middle Aged; D023421:Models, Animal; D013744:Tetanus Toxin / Q000276:immunology*; D013745:Tetanus Toxoid / Q000008:administration & dosage / Q000276:immunology*; D014611:Vaccination
D000907:Antibodies, Bacterial; D007074:Immunoglobulin G; D013744:Tetanus Toxin; D013745:Tetanus Toxoid