The purpose of the study is to determine if immunization with a recombinant E. coli protein, dscCfaE, is safe and immunogenic when administered through the skin using a patch.
The purpose of the study is to determine if immunization with dscCfaE with or without a modified E. coli heat labile enterotoxin, LTR192G, is safe and immunogenic when administered transcutaneously using a skin wet-patch. If the vaccine is found safe and adequately immunogenic in humans, a phase 2b vaccination/challenge study would be undertaken to further evaluate vaccine safety and allow a preliminary assessment of efficacy. With favorable evidence for safety, immunogenicity, efficacy, complemented by advances in standard methodology to combine multiple adhesins with an appropriate LT enterotoxoid form, a multivalent vaccine would be constructed and evaluated for further clinical development.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
NONE
Enrollment
40
10 ug on study days 0, 21 and 42
50 ug on study days 0, 21 and 42
250 ug on study days 0, 21 and 42
Walter Reed Army Institute of Research Clinical Trial Center
Silver Spring, Maryland, United States
Number of adverse events
Adverse event monitoring will survey and specifically inquire about fever (oral temperature \> 100.4 o F), malaise, headache, rash, pain, diarrhea, abdominal pain, extremity pain or swelling. Clinical definitions will be used to grade severity of symptoms in accordance to the severity scale below: Grade 0 = None Grade 1= Barely noticeable Grade 2= Noticeable, does not interfere with daily activities Grade 3=Interferes with daily activities Grade 4=Prevents daily activities
Time frame: Days 0 - 180
Number of Seroconversion to LT and dscCfaE; defined as a > 4-fold increase in endpoint titer between pre-and post-vaccination samples.
Time frame: Study Days 0 - 180
Number of Mucosal responses (fecal IgA); defined as a > 4-fold increase in endpoint titer after adjusting for total IgA.
Time frame: Study Days 0 - 180
Number of positive IgA-ASC responses; defined as a > 2-fold increase over th e baseline value of the ASC per 10 6 PBMC, when the number of ASC is > 0.5 per 10 6 in the baseline sample
A positive IgA-ASC response will be defined as a \> 2-fold increase over th e baseline value of the ASC per 10 6 PBMC, when the number of ASC is \> 0.5 per 10 6 in the baseline sample. When the number of baseline ASCs is less than 0.5 per 10 6 PBMC, a subject will be considered a responder if the post-vaccination value is greater than 1.0 per 10 6 PBMC
Time frame: Study Days 0 - 180
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50 ug on study days 0, 21 and 42