• Biomolecules & Therapeutics
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• v.6 no.2
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• pp.191-198
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• 1998

Vsrio vulnificus is an estuarine gram-negative human pathogen that affects people with chronic hepatitis, alcoholic cirrhosis, diabetes mellitus or other underlying diseases. V. vulnificus infection is mediated primarily by consumption of raw fish or by exposure of pre-existing wounds to seawater, causing permanent tissue damages or fatal septic shock. We have been developing a vaccine against V. vulnificus composed of whole cell Iysate of a V. vulnificus O-antigen serotype 4 strain. Oral administration of the V. vulnificus;oral vaccine;immunogenicity;protective efficacy vaccine elicited a high serum antibody response in rabbits. The induced antibodies were reactive not only to the homologous strain but also to heterologous O-antigen serotype strains, indicating cross-reactivities among serotypes. Western blot analysis revealed that the antibodies are mainly specific for outer membrane proteins (OMPs) and reacted equally well with OMPs purified from 9 O-antigen serotypes. The rabbit antisera showed opsonophagocytic killing activity against heterologous strains as well as the homologous strain. Passively transferred rabbit antisera into mice were protective against a lethal V. vulnificus infection. These data demonstrate that oral administration of the V. vulnificus vaccine induced a systemic antibody response which had a protective efficacy against V. vulnificus infections, suggesting that this vaccine preparation could be used to develop an oral vaccine against V. vulnificus.

• Journal of Microbiology and Biotechnology
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• v.7 no.6
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• pp.423-428
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• 1997

Vibrio vulnificus is a halophilic gram-negative human pathogen, which affects people with underlying liver diseases or a suppressed immune system, often leading to primary septicemia with a mortality rate of higher than 60%. In an effort to develop an oral vaccine against V. vulnificus infection, we prepared a whole cell killed vaccine of V. vulnificus on a large scale and compared the immunogenicity and protective efficacy of the vaccine administered in three formulation forms in rabbits. Since V. vulnificus O-antigen serotypes 1, 2, 3, 4, 5, and 7 account for more than 95% of clinical isolates, we prepared cell lysates from these six serotype strains and mixed in equal amounts for a vaccine. The vaccine was administered to rabbits intramuscularly (i.m.), orally as granules or as enteric-coated granules. In rabbits, all three formulation forms elicited a high level of serum IgG antibody reactive not only to the six strains but also to other O-antigen serotypes 6, 8 and 9, indicating cross-reactivities among the strains. Immunotherapeutic efficacy of the antisera was also evaluated by a passive immunization assay, which revealed that the orally immunized antisera as well as the i.m. immunized antisera was protective against a subsequent lethal challenge of V. vulnificus. These data demonstrate that oral immunization with a V. vulnificus whole cell lysate vaccine induced a systemic immune response and suggest the feasibility of development of this vaccine preparation as an oral vaccine.

• Biomolecules & Therapeutics
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• v.7 no.1
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• pp.89-96
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• 1999

CJ-50002 is an oral vaccine against V.vulnificus infection composed of whole cell lysate of V. vulnificus. The general pharmacological properties of CJ-50002 were evaluated in various animals and in vitro system. CJ-50002 at oral doses of 0.2, 2 and 20 mg/kg had no effect on general behavior in mice, chromo- and electro-convulsions in mice, writhing syndrome induced by acetic acid in mice, body temperature in rats, charcoal meal propulsion in mice and urine and electrolytes excretion in rats. However, oral administration of CJ-50002 at dose of 20 mg/kg prolonged the hexobarbital-inuced sleeping inducing time in mice. In anesthetized dogs, CJ-50002 showed no effect on blood pressure, heart rate and ECG but decreased the respiratory rate and femoral blood flow at dose of 20 mg/kg. p.o. CJ-50002 had no effect on the contractile response of the isolated guinea pig ileum to various spasmogen at concentrations of 0.2, 2 and 20 $\mu\textrm{g}$/ml, respectively. Since these pharmacological effects of CJ-500o2 were observed at dose much greater than those in clinical use (approximately 0.16 mg/kg, p.o.), it is likely that this vaccine may be relatively free of undesirable effects in clinical practice.