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document
Safety and immunogenicity of an oral , inactivated , whole-cell vaccine for Shigella sonnei : preclinical studies and a Phase I trial . Orally delivered , inactivated whole-cell vaccines are safe methods of inducing local and systemic immunity . To increase surface proteins associated with adherence and invasion , Shigella sonnei were grown in BHI broth containing deoxycholate . A whole-cell vaccine ( SsWC ) was then produced by formalin inactivation . In pre-clinical studies , the SsWC vaccine was immunogenic and protected against S. sonnei-induced keratoconjunctivitis in the guinea pig model . In a randomized , double-blind , placebo-controlled , Phase I study , 10 evaluable subjects received either three doses of SsWC on Days 0 , 14 , and 28 ( N = 3 ) ; five doses of SsWC on Days 0 , 2 , 4 , 6 , and 28 ( N = 4 ) ; or placebo ( N = 3 ) . Each dose contained 2.0 x 10 ( 10 ) inactivated cells . Serum and fecal antibodies against SsWC , LPS , and IpaC were measured by ELISA . A > or = 4-fold increase in titer was considered significant . Both SsWC dosing regimens were well tolerated . No fever or severe gastrointestinal symptoms were noted by any of the vaccinated subjects . Antibody responses were similar in the two dosing groups . Serum IgG or IgA responses to SsWC were seen in six of seven vaccinees ( 86 % ) , to LPS in four of seven ( 57 % ) , and to IpaC in five of seven ( 61 % ) . Fecal IgA responses to these three antigens developed in five of five , three of five , and three of five subjects , respectively . Among the seven vaccinees , geometric mean rises in serum IgA levels to all three immunogens were significant ; IgG increases trended toward significance ( paired one-tailed t-test ) . We conclude that SsWC was immunogenic and protective in animal studies and well tolerated and immunogenic in a Phase I trial .
23091
Intervention_Pharmacological
oral , inactivated , whole-cell vaccine for Shigella sonnei
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Intervention_Pharmacological
vaccines
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Intervention_Pharmacological
whole-cell vaccine ( SsWC )
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Intervention_Pharmacological
SsWC vaccine
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Intervention_Control
placebo-controlled
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Intervention_Pharmacological
SsWC
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Intervention_Pharmacological
SsWC
23098
Intervention_Control
placebo
23099
Intervention_Pharmacological
SsWC
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Intervention_Pharmacological
SsWC
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Intervention_Pharmacological
SsWC
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Outcome_Physical
surface proteins
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Outcome_Physical
Serum and fecal antibodies against SsWC , LPS , and IpaC
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Outcome_Other
tolerated
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Outcome_Adverse-effects
fever or severe gastrointestinal symptoms
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Outcome_Physical
Antibody responses
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Outcome_Physical
Serum IgG or IgA responses
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Outcome_Physical
Fecal IgA responses
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Outcome_Physical
serum IgA levels
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Outcome_Physical
IgG increases
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Outcome_Other
protective
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Outcome_Other
tolerated