Topical application of Escherichia coli-vectored vaccine as a simple method for eliciting protective immunity.
We report here that animals can be protected against lethal infection by Clostridium tetani cells and Bacillus anthracis spores following topical application of intact particles of live or gamma-irradiated Escherichia coli vectors overproducing tetanus and anthrax antigens, respectively. Cutaneous gammadeltaT cells were rapidly recruited to the administration site. Live E. coli cells were not found in nonskin tissues after topical application, although fragments of E. coli DNA were disseminated transiently. Evidence suggested that intact E. coli particles in the outer layer of skin may be disrupted by a gammadeltaT-cell-mediated innate defense mechanism, followed by the presentation of E. coli ligand-adjuvanted intravector antigens to the immune system and rapid degradation of E. coli components. The nonreplicating E. coli vector overproducing an exogenous immunogen may foster the development of a new generation of vaccines that can be manufactured rapidly and administered noninvasively in a wide variety of disease settings.
Zhang
Jianfeng
J
Vaxin Inc., 2800 Milan Court, Birmingham, AL 35211, USA.
Shi
Zhongkai
Z
Kong
Fan-Kun
FK
Jex
Edward
E
Huang
Zhigang
Z
Watt
James M
JM
Van Kampen
Kent R
KR
Tang
De-Chu C
DC
D000287:Administration, Topical; D000818:Animals; D000881:Anthrax / Q000517:prevention & control; D000907:Antibodies, Bacterial / Q000097:blood; D001426:Bacterial Proteins / Q000276:immunology; D001483:Base Sequence; D004926:Escherichia coli / Q000528:radiation effects; D022361:Escherichia coli Vaccines / Q000008:administration & dosage*; D005260:Female; D005720:Gamma Rays; D051379:Mice; D008813:Mice, Inbred ICR; D008969:Molecular Sequence Data; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000502:physiology; D012097:Repressor Proteins / Q000276:immunology; D012867:Skin / Q000276:immunology*; D013601:T-Lymphocytes / Q000502:physiology; D013742:Tetanus / Q000517:prevention & control; D014611:Vaccination
D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D022361:Escherichia coli Vaccines; D016692:Receptors, Antigen, T-Cell, gamma-delta; D012097:Repressor Proteins; C107173:TetC protein, Bacteria