Efficacy, heat stability and safety of intranasally administered Bacillus subtilis spore or vegetative cell vaccines expressing tetanus toxin fragment C

被引:37
作者
Lee, Sangun [1 ]
Belitsky, Boris R. [2 ]
Brown, David W. [1 ]
Brinker, James P. [1 ]
Kerstein, Kathryn O. [2 ]
Herrmann, John E. [1 ]
Keusch, Gerald T. [3 ]
Sonenshein, Abraham L. [2 ]
Tzipori, Saul [1 ]
机构
[1] Tufts Univ, Cummings Sch Vet Med, Div Infect Dis, North Grafton, MA 01536 USA
[2] Tufts Univ, Sch Med, Dept Mol Biol & Microbiol, Boston, MA 02111 USA
[3] Boston Univ, Sch Publ Hlth, Dept Int Hlth, Boston, MA 02118 USA
关键词
Tetanus; Vaccine; B; subtilis; CRYPTOSPORIDIUM-PARVUM; VACCINATION; INTEGRATION; DIPHTHERIA; PERTUSSIS; DELIVERY; VECTORS; GENES;
D O I
10.1016/j.vaccine.2010.08.016
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
071005 [微生物学]; 100108 [医学免疫学];
摘要
Bacillus subtilis strains expressing tetanus toxin fragment C (TTFC) were tested as vaccine candidates against tetanus in adult mice. Mice received three intranasal (IN) exposures to 10(9) spores or 10(8) vegetative cells of B. subtilis expressing recombinant MC. Immunized mice generated protective systemic and mucosal antibodies and survived challenge with 2x LD100 of tetanus toxin. Isotype analysis of serum antibody indicated a balanced Th1/Th2 response. Lyophilized vaccines stored at 45 degrees C for >= 12 months, remained effective. Immunized conventional and SCID mice remained well, and no histological changes in brain or respiratory tract were detected. Lyophilized/reconstituted B. subtilis tetanus vaccines administered IN to mice appear safe, heat-stable, and protective against lethal tetanus challenge. (C) 2010 Elsevier Ltd. All rights reserved.
引用
收藏
页码:6658 / 6665
页数:8
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