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An enterotoxigenic Escherichia coli (ETEC) vaccine could reduce diarrhea among children in developing countries and travelers to these countries. The heat-labile toxin (LT) of ETEC is immunogenic but too toxic for oral or nasal vaccines. In a double-blind, placebo-controlled trial, 59 adults were randomized to receive 50 μg of LT or placebo in a patch applied to alternating arms on days 0, 21, and 42. On day 56, 27 vaccinees and 20 controls were challenged orally with 6 × 10 8 cfu of LT +/ST + ETEC. 100 and 97% of vaccinees had 4-fold increases in anti-LT IgG and IgA, and 100 and 90% developed IgG- and IgA-antibody-secreting cell responses. The study did not meet the primary endpoint: 82% of vaccinees and 75% of controls had moderate to severe ETEC illness. However, vaccinees with ETEC illness had lower numbers (6.8 versus 9.7, p = 0.04) and weights of loose stools (840 g versus 1147 g, p < 0.05), a decreased need for intravenous fluids (14% versus 40%, p = 0.03) and a delayed onset of diarrhea (30 h versus 22 h, p = 0.01). Transcutaneous LT vaccination induced anti-toxin immune responses that did not prevent but mitigated illness following a high-dose challenge with a virulent LT +/ST + ETEC strain.

Among Shigella serotypes Shigella dysenteriae type 1 produces the most severe disease, including cases of hemolytic-uremic syndrome and pandemic outbreaks. WRSd1 is a live S. dysenteriae 1 strain attenuated by deletion of the virG( icsA) gene, which encodes a protein that mediates intercellular spread, and stxA and stxB, which encode the Shiga toxin. In this Phase I trial five groups of eight subjects ingested escalating doses of WRSd1 ranging from 10 3 to 10 7 CFU. No subject experienced fever or shigellosis, but 20% had diarrhea. Approximately two-thirds of subjects developed an IgA-ASC response to LPS. Days of fecal shedding of the vaccine strain, but not dose ingested, correlated with stronger immune responses. These results suggest that to be effective an attenuated Shigella vaccine must colonize well.

AmongShigellaserotypesShigella dysenteriaetype 1 produces the most severe disease, including cases of hemolytic-uremic syndrome and pandemic outbreaks. WRSd1 is a liveS. dysenteriae1 strain attenuated by deletion of thevirG(icsA) gene, which encodes a protein that mediates intercellular spread, andstxAandstxB, which encode the Shiga toxin. In this Phase I trial five groups of eight subjects ingested escalating doses of WRSd1 ranging from 103to 107CFU. No subject experienced fever or shigellosis, but 20% had diarrhea. Approximately two-thirds of subjects developed an IgA-ASC response to LPS. Days of fecal shedding of the vaccine strain, but not dose ingested, correlated with stronger immune responses. These results suggest that to be effective an attenuatedShigellavaccine must colonize well.

Background An enterotoxigenicEscherichia coli(ETEC) vaccine could reduce diarrhea among children in developing countries and travelers to these countries. The heat-labile toxin (LT) of ETEC is immunogenic but too toxic for oral or nasal vaccines. Methods In a double-blind, placebo-controlled trial, 59 adults were randomized to receive 50μg of LT or placebo in a patch applied to alternating arms on days 0, 21, and 42. On day 56, 27 vaccinees and 20 controls were challenged orally with 6x108cfu of LT+/ST+ETEC. Results 100 and 97% of vaccinees had 4-fold increases in anti-LT IgG and IgA, and 100 and 90% developed IgG- and IgA-antibody-secreting cell responses. The study did not meet the primary endpoint: 82% of vaccinees and 75% of controls had moderate to severe ETEC illness. However, vaccinees with ETEC illness had lower numbers (6.8 versus 9.7,p=0.04) and weights of loose stools (840g versus 1147g,p<0.05), a decreased need for intravenous fluids (14% versus 40%,p=0.03) and a delayed onset of diarrhea (30h versus 22h,p=0.01). Conclusions Transcutaneous LT vaccination induced anti-toxin immune responses that did not prevent but mitigated illness following a high-dose challenge with a virulent LT+/ST+ETEC strain.

I have been reading with extreme interest about the question of desegregation between Hartford and it suburbs. Frankly, a desegregation plan, if it is put into place, is doomed to failure. It would short-circuit other plans that are more workable and have greater potential to achieve the plaintiffs' goals and assuage suburban concerns.

I have been reading with extreme interest, about the question of desegregation between Hartford and it suburbs. Frankly, a desegregation plan, if it is put into place, is doomed to failure. It would short-circuit other plans that are more workable and have greater potential to achieve the plaintiffs' goals and assuage suburban concerns.

I have been reading with extreme interest about the question of desegregation between Hartford and it suburbs. Frankly, a desegregation plan, if it is put into place, is doomed to failure. It would short-circuit other plans that are more workable and have greater potential to achieve the plaintiffs' goals and assuage suburban concerns.

I have been reading with extreme interest about the question of desegregation between Hartford and it suburbs. Frankly, a desegregation plan, if it is put into place, is doomed to failure. It would short-circuit other plans that are more workable and have greater potential to achieve the plaintiffs' goals and assuage suburban concerns.

I have been reading with extreme interest about the question of desegregation between Hartford and it suburbs. Frankly, a desegregation plan, if it is put into place, is doomed to failure. It would short-circuit other plans that are more workable and have greater potential to achieve the plaintiffs' goals and assuage suburban concerns.

I have been reading with extreme interest about the question of desegregation between Hartford and it suburbs. Frankly, a desegregation plan, if it is put into place, is doomed to failure. It would short-circuit other plans that are more workable and have greater potential to achieve the plaintiffs' goals and assuage suburban concerns.