human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: ABSTRACT Enterotoxigenic Escherichia coli ( ETEC ) is one of the leading causes of diarrhea among Israeli soldiers serving in field units . Two double-blind placebo-controlled , r and omized trials were performed among 155 healthy volunteers to evaluate the safety and immunogenicity of different lots of the oral , killed ETEC vaccine consisting of two doses of whole cells plus recombinantly produced cholera toxin B subunit ( rCT B ) . The two doses of vaccine lot E005 and the first dose of vaccine lot E003 were well tolerated by the volunteers . However , 5 ( 17 % ) vaccinees reported an episode of vomiting a few hours after the second dose of lot E003 ; none of the placebo recipients reported similar symptoms . Both lots of vaccine stimulated a rate of significant antibody-secreting cell ( ASC ) response to CTB and to colonization factor antigen I ( CFA/I ) after one or two doses , ranging from 85 to 100 % and from 81 to 100 % , respectively . The rate of ASC response to CS2 , CS4 , and CS5 was slightly lower than the rate of ASC response induced to CTB , CFA/I , and CS1 . The second vaccine dose enhanced the response to CTB but did not increase the frequencies or magnitude of ASC responses to the other antigens . The two lots of the ETEC vaccine induced similar rates of serum antibody responses to CTB and CFA/I which were less frequent than the ASC responses to the same antigens . Based on these safety and immunogenicity data , an efficacy study of the ETEC vaccine is under way in the Israel Defense Force Two r and omized , double-blinded trials assessed the safety and immunogenicity of an oral , killed enterotoxigenic Escherichia coli ( ETEC ) plus cholera toxin B subunit vaccine in Egyptian children . Two doses of vaccine or E. coli K-12 were given 2 weeks apart to 105 6- to 12-year-olds and 97 2- to 5-year-olds .  Safety was monitored for 3 days after each dose . Blood was collected before immunization and 7 days after each dose to measure immune responses . Few children reported postdosing symptoms , with no differences in the frequency of symptoms between treatment groups . Most vaccinees had an IgA antibody-secreting cell response against colonization factor antigen I ( 100 % , 6 - 12 years ; 95 % , 2 - 5 years ) , coli surface antigen 2 ( 92 % , 6 - 12 years ; 83 % , 2 - 5 years ) , and coli surface antigen 4 ( 93 % , 6 - 12 years ) . Vaccination evoked a > /=4-fold rise in antitoxic IgA and IgG titers in 93 % and 81 % of children , respectively . In conclusion , the oral ETEC vaccine was safe and immunogenic in 2- to 12-year-old children , justifying further evaluation in infants Enterotoxigenic E. coli ( ETEC ) are an important cause of diarrhea in developing countries , especially among indigenous children and travelers . In this r and omized , double-blind , placebo-controlled trial , a live , attenuated CS1/CS3 ETEC strain , PTL-003 , was tested as a potential vaccine strain . Thirty-three subjects drank buffered solutions containing either PTL-003 or placebo on Days 0 and 10 and were challenged with virulent CS1/CS3 ETEC strain E24377A on Day 28 . The vaccine did not protect against moderate to severe ETEC illness ( the primary endpoint ) , but it did prime subjects for a rapid antibody response to CS1 and CS3 after challenge , suggesting that a dose of vaccine on Day 28 might improve the immune response to the vaccine . Higher serum anti-CS3 IgA titers at the time of challenge correlated with less severe diarrheal illness Orally administered bovine immunoglobulins with specific activity against colonization factors of enterotoxigenic Escherichia coli ( ETEC ) could provide passive protection against ETEC challenge in volunteers . Twenty healthy adult volunteers ingested either a placebo or a partially enteric-coated preparation of bovine immunoglobulins with activity against the colonization factor antigens CFA/I , CS3 , and CS6 and then were challenged with ETEC strain E24377A ( CS1 + , CS3 + ) administered with a st and ard meal . There was no difference in the incidence or severity of diarrhea among the 10 volunteers who received the bovine immunoglobulins and the 10 who received placebo . Either the specificity or titer of anti-colonization factor antibodies or the formulation of antibodies in this product was not adequate to provide passive protection against ETEC challenge Low dose E. coli heat-labile enterotoxin ( LT ) , delivered orally or enterically , has been used as an adjuvant for Helicobacter pylori ( H. pylori ) urease in healthy adults . In this study we aim to test the safety and adjuvant efficacy of LT delivered rectally together with recombinant H. pylori urease .  Eighteen healthy adults without present or past H. pylori infection were enrolled in a double blind , r and omized , ascending dose study to receive either urease ( 60 mg ) , or urease ( 60 mg ) + LT ( 5 or 25 microg ) . The immunization preparation was administered per rectum on days 0 , 14 and 28 . Serum , stool and saliva anti-urease and anti-LT IgG and IgA antibodies ( Abs ) were measured and urease-specific and LT-specific antigen secreting cells ( ASCs ) were counted in peripheral blood at baseline and 7 ( ASC counts ) or 14 days ( antibody levels ) after each dosing . Peripheral blood lymphoproliferation assays were also performed at baseline and at the end of the study . Rectally delivered urease and LT were well tolerated . Among the 12 subjects assigned to urease+LT , 2 ( 16.7 % ) developed anti-urease IgG Abs , 1 ( 8.3 % ) developed anti-urease IgA Abs , and 3 ( 25 % ) showed urease-specific IgA(+ ) ASCs . Immune responses to LT were more vigorous , especially in subjects exposed to 5 microg LT . In the urease+ 5 microg LT group , anti-LT IgG and IgA Abs developed in 60 and 80 % of the subjects , respectively , while LT-specific IgG(+ ) and IgA(+ ) ASCs were detected in all subjects . The magnitude of the anti-LT response was much higher than the response to urease . No IgA anti-urease or anti-LT Abs were detected in stool or saliva and lymphocyte proliferative responses to urease were unsatisfactory . In conclusion , rectal delivery of 5 microg LT is safe and induces vigorous systemic anti-LT immune responses . Further studies are needed to determine if LT can be an effective adjuvant for rectally delivered antigens A phase II safety and immunogenicity study of an oral-formalin inactivated enterotoxigenic Escherichia coli ( ETEC ) vaccine containing six colonization factors ( CFA/I , CS1 , CS2 , CS3 , CS4 , CS5 ) and 1 mg of recombinant cholera toxin B subunit ( the CF-BS-ETEC vaccine ) was carried out in an urban slum of Dhaka city in Bangladesh . The study was carried out in a double blinded , placebo controlled design in 158 children , 18 - 36 months of age . Children were given two doses of the CF-BS-ETEC vaccine or the placebo which consisted of E. coli K12 . The vaccine was well tolerated . The immune response was studied in 60 children ( 30 each in the placebo and vaccine group ) . Significant vaccine specific IgA antibody-secreting cell ( ASC ) responses were seen 7 days after ingestion of the first and second dose of the vaccine . The responses to CFA/I ( P < or=0.001 ) , CS2 ( P=0.021 ) , CS4 ( P=0.009 ) and rCT B ( P < or=0.001 ) were elevated in the vaccines in comparison to the pre-immune values and in comparison to those seen in the placebo recipients ( P=0.018 to < 0.001 ) . Vaccines but not placebo recipients also showed significantly increased IgM ASC responses to all three CF antigens that were tested ( P=0.012 to < 0.001 ) and IgG-ASCs to rCT B ( P<0.001 ) . Peak ASC levels were reached after one dose of the vaccine with no further increase or decrease after the second dose . The vaccine recipients also responded with IgA plasma antibodies to CFA/I , CS1 , CS2 , CS4 and rCT B after one or two doses of the vaccine ( P=0.01 to < 0.001 ) . Subjects in the placebo group failed to mount responses to any of the antigens . The vaccine also induced responses in mucosal IgA antibodies in feces to CFA/I , CS2 and rCT B ( 61 , 88 and 69 % responder frequency , respectively ) and the magnitude of the response was elevated in comparison to the pre-immune levels ( P=0.031 to < 0.001 ) and to the levels of the control group ( P=0.003 to < 0.001 ) . This study thus shows that the CF-BS-ETEC vaccine is well tolerated in children , 18 - 36 months of age and gives rise to significant systemic and mucosal IgA antibody responses Serum responses to oral cholera vaccines were assessed in three paediatric vaccine trials , two in León , Nicaragua and one in Stockholm , Sweden . A calibrated anti-cholera toxin B subunit ( CTB ) IgA ELISA was used together with an assay for vibriocidal antibodies . Swedish children had lower pre-vaccination levels of antibody , but serum responses were more pronounced in Swedish children than in Nicaraguan children .  Post-vaccination levels of anti-toxin antibody were generally above those found after natural infections with enterotoxigenic Escherichia coli , that cross-reacts serologically with Vibrio cholerae . Adverse events seen after vaccination were generally mild and of little clinical significance Vaccine regimens which mimic actual infection with bacterial enteropathogens should offer the best opportunity for successful long-term immunoprotection against diarrheal disease caused by enterotoxigenic Escherichia coli ( ETEC ) or Vibrio cholerae . Based on this principle , we design ed and tested an oral whole cell anti-ETEC vaccine consisting of intact cells of ETEC strain H-10407 ( ST+LT+ ; O78:H11:CFA/I ) which were rendered incapable of replication by treatment with a potent DNA endonuclease , colicin E2 . Young healthy volunteers were administered two oral doses of either placebo or approx . 3 X 10(10 ) vaccine cells . In a double-blind study , 9 of 10 vaccinees responded with an increase in CFA/I-specific intestinal IgA antibody , determined as percent of total IgA. Challenge with virulent strain H-10407 ( 5 X 10(9 ) living cells ) produced diarrhea in 8 of 9 ( 89 % ) of the placebo-treated volunteers and in 2 of 10 ( 20 % ) of the vaccinees . Thus , the colicin E2-killed whole cell vaccine afforded both a significant intestinal immune response and significant protection against challenge with the virulent organism . The data presented here suggest that for this vaccine preparation an intestinal anti-CFA/I IgA response is a good indicator of a protective immune response , which most likely involves antibody responses to a number of antigens in addition to CFA/I. We conclude that the colicin E2 method for preparing an oral anti-ETEC vaccine merits further study and that this method may also be applicable to other enteropathogens BACKGROUND 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 . METHODS In a double-blind , placebo-controlled trial , 59 adults were r and omized to receive 50 microg 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 6x10(8 ) cfu 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 , vaccine 
    Output:
    
agent
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: ABSTRACT Enterotoxigenic Escherichia coli ( ETEC ) is one of the leading causes of diarrhea among Israeli soldiers serving in field units . Two double-blind placebo-controlled , r and omized trials were performed among 155 healthy volunteers to evaluate the safety and immunogenicity of different lots of the oral , killed ETEC vaccine consisting of two doses of whole cells plus recombinantly produced cholera toxin B subunit ( rCT B ) . The two doses of vaccine lot E005 and the first dose of vaccine lot E003 were well tolerated by the volunteers . However , 5 ( 17 % ) vaccinees reported an episode of vomiting a few hours after the second dose of lot E003 ; none of the placebo recipients reported similar symptoms . Both lots of vaccine stimulated a rate of significant antibody-secreting cell ( ASC ) response to CTB and to colonization factor antigen I ( CFA/I ) after one or two doses , ranging from 85 to 100 % and from 81 to 100 % , respectively . The rate of ASC response to CS2 , CS4 , and CS5 was slightly lower than the rate of ASC response induced to CTB , CFA/I , and CS1 . The second vaccine dose enhanced the response to CTB but did not increase the frequencies or magnitude of ASC responses to the other antigens . The two lots of the ETEC vaccine induced similar rates of serum antibody responses to CTB and CFA/I which were less frequent than the ASC responses to the same antigens . Based on these safety and immunogenicity data , an efficacy study of the ETEC vaccine is under way in the Israel Defense Force Two r and omized , double-blinded trials assessed the safety and immunogenicity of an oral , killed enterotoxigenic Escherichia coli ( ETEC ) plus cholera toxin B subunit vaccine in Egyptian children . Two doses of vaccine or E. coli K-12 were given 2 weeks apart to 105 6- to 12-year-olds and 97 2- to 5-year-olds .  Safety was monitored for 3 days after each dose . Blood was collected before immunization and 7 days after each dose to measure immune responses . Few children reported postdosing symptoms , with no differences in the frequency of symptoms between treatment groups . Most vaccinees had an IgA antibody-secreting cell response against colonization factor antigen I ( 100 % , 6 - 12 years ; 95 % , 2 - 5 years ) , coli surface antigen 2 ( 92 % , 6 - 12 years ; 83 % , 2 - 5 years ) , and coli surface antigen 4 ( 93 % , 6 - 12 years ) . Vaccination evoked a > /=4-fold rise in antitoxic IgA and IgG titers in 93 % and 81 % of children , respectively . In conclusion , the oral ETEC vaccine was safe and immunogenic in 2- to 12-year-old children , justifying further evaluation in infants Enterotoxigenic E. coli ( ETEC ) are an important cause of diarrhea in developing countries , especially among indigenous children and travelers . In this r and omized , double-blind , placebo-controlled trial , a live , attenuated CS1/CS3 ETEC strain , PTL-003 , was tested as a potential vaccine strain . Thirty-three subjects drank buffered solutions containing either PTL-003 or placebo on Days 0 and 10 and were challenged with virulent CS1/CS3 ETEC strain E24377A on Day 28 . The vaccine did not protect against moderate to severe ETEC illness ( the primary endpoint ) , but it did prime subjects for a rapid antibody response to CS1 and CS3 after challenge , suggesting that a dose of vaccine on Day 28 might improve the immune response to the vaccine . Higher serum anti-CS3 IgA titers at the time of challenge correlated with less severe diarrheal illness Orally administered bovine immunoglobulins with specific activity against colonization factors of enterotoxigenic Escherichia coli ( ETEC ) could provide passive protection against ETEC challenge in volunteers . Twenty healthy adult volunteers ingested either a placebo or a partially enteric-coated preparation of bovine immunoglobulins with activity against the colonization factor antigens CFA/I , CS3 , and CS6 and then were challenged with ETEC strain E24377A ( CS1 + , CS3 + ) administered with a st and ard meal . There was no difference in the incidence or severity of diarrhea among the 10 volunteers who received the bovine immunoglobulins and the 10 who received placebo . Either the specificity or titer of anti-colonization factor antibodies or the formulation of antibodies in this product was not adequate to provide passive protection against ETEC challenge Low dose E. coli heat-labile enterotoxin ( LT ) , delivered orally or enterically , has been used as an adjuvant for Helicobacter pylori ( H. pylori ) urease in healthy adults . In this study we aim to test the safety and adjuvant efficacy of LT delivered rectally together with recombinant H. pylori urease .  Eighteen healthy adults without present or past H. pylori infection were enrolled in a double blind , r and omized , ascending dose study to receive either urease ( 60 mg ) , or urease ( 60 mg ) + LT ( 5 or 25 microg ) . The immunization preparation was administered per rectum on days 0 , 14 and 28 . Serum , stool and saliva anti-urease and anti-LT IgG and IgA antibodies ( Abs ) were measured and urease-specific and LT-specific antigen secreting cells ( ASCs ) were counted in peripheral blood at baseline and 7 ( ASC counts ) or 14 days ( antibody levels ) after each dosing . Peripheral blood lymphoproliferation assays were also performed at baseline and at the end of the study . Rectally delivered urease and LT were well tolerated . Among the 12 subjects assigned to urease+LT , 2 ( 16.7 % ) developed anti-urease IgG Abs , 1 ( 8.3 % ) developed anti-urease IgA Abs , and 3 ( 25 % ) showed urease-specific IgA(+ ) ASCs . Immune responses to LT were more vigorous , especially in subjects exposed to 5 microg LT . In the urease+ 5 microg LT group , anti-LT IgG and IgA Abs developed in 60 and 80 % of the subjects , respectively , while LT-specific IgG(+ ) and IgA(+ ) ASCs were detected in all subjects . The magnitude of the anti-LT response was much higher than the response to urease . No IgA anti-urease or anti-LT Abs were detected in stool or saliva and lymphocyte proliferative responses to urease were unsatisfactory . In conclusion , rectal delivery of 5 microg LT is safe and induces vigorous systemic anti-LT immune responses . Further studies are needed to determine if LT can be an effective adjuvant for rectally delivered antigens A phase II safety and immunogenicity study of an oral-formalin inactivated enterotoxigenic Escherichia coli ( ETEC ) vaccine containing six colonization factors ( CFA/I , CS1 , CS2 , CS3 , CS4 , CS5 ) and 1 mg of recombinant cholera toxin B subunit ( the CF-BS-ETEC vaccine ) was carried out in an urban slum of Dhaka city in Bangladesh . The study was carried out in a double blinded , placebo controlled design in 158 children , 18 - 36 months of age . Children were given two doses of the CF-BS-ETEC vaccine or the placebo which consisted of E. coli K12 . The vaccine was well tolerated . The immune response was studied in 60 children ( 30 each in the placebo and vaccine group ) . Significant vaccine specific IgA antibody-secreting cell ( ASC ) responses were seen 7 days after ingestion of the first and second dose of the vaccine . The responses to CFA/I ( P < or=0.001 ) , CS2 ( P=0.021 ) , CS4 ( P=0.009 ) and rCT B ( P < or=0.001 ) were elevated in the vaccines in comparison to the pre-immune values and in comparison to those seen in the placebo recipients ( P=0.018 to < 0.001 ) . Vaccines but not placebo recipients also showed significantly increased IgM ASC responses to all three CF antigens that were tested ( P=0.012 to < 0.001 ) and IgG-ASCs to rCT B ( P<0.001 ) . Peak ASC levels were reached after one dose of the vaccine with no further increase or decrease after the second dose . The vaccine recipients also responded with IgA plasma antibodies to CFA/I , CS1 , CS2 , CS4 and rCT B after one or two doses of the vaccine ( P=0.01 to < 0.001 ) . Subjects in the placebo group failed to mount responses to any of the antigens . The vaccine also induced responses in mucosal IgA antibodies in feces to CFA/I , CS2 and rCT B ( 61 , 88 and 69 % responder frequency , respectively ) and the magnitude of the response was elevated in comparison to the pre-immune levels ( P=0.031 to < 0.001 ) and to the levels of the control group ( P=0.003 to < 0.001 ) . This study thus shows that the CF-BS-ETEC vaccine is well tolerated in children , 18 - 36 months of age and gives rise to significant systemic and mucosal IgA antibody responses Serum responses to oral cholera vaccines were assessed in three paediatric vaccine trials , two in León , Nicaragua and one in Stockholm , Sweden . A calibrated anti-cholera toxin B subunit ( CTB ) IgA ELISA was used together with an assay for vibriocidal antibodies . Swedish children had lower pre-vaccination levels of antibody , but serum responses were more pronounced in Swedish children than in Nicaraguan children .  Post-vaccination levels of anti-toxin antibody were generally above those found after natural infections with enterotoxigenic Escherichia coli , that cross-reacts serologically with Vibrio cholerae . Adverse events seen after vaccination were generally mild and of little clinical significance Vaccine regimens which mimic actual infection with bacterial enteropathogens should offer the best opportunity for successful long-term immunoprotection against diarrheal disease caused by enterotoxigenic Escherichia coli ( ETEC ) or Vibrio cholerae . Based on this principle , we design ed and tested an oral whole cell anti-ETEC vaccine consisting of intact cells of ETEC strain H-10407 ( ST+LT+ ; O78:H11:CFA/I ) which were rendered incapable of replication by treatment with a potent DNA endonuclease , colicin E2 . Young healthy volunteers were administered two oral doses of either placebo or approx . 3 X 10(10 ) vaccine cells . In a double-blind study , 9 of 10 vaccinees responded with an increase in CFA/I-specific intestinal IgA antibody , determined as percent of total IgA. Challenge with virulent strain H-10407 ( 5 X 10(9 ) living cells ) produced diarrhea in 8 of 9 ( 89 % ) of the placebo-treated volunteers and in 2 of 10 ( 20 % ) of the vaccinees . Thus , the colicin E2-killed whole cell vaccine afforded both a significant intestinal immune response and significant protection against challenge with the virulent organism . The data presented here suggest that for this vaccine preparation an intestinal anti-CFA/I IgA response is a good indicator of a protective immune response , which most likely involves antibody responses to a number of antigens in addition to CFA/I. We conclude that the colicin E2 method for preparing an oral anti-ETEC vaccine merits further study and that this method may also be applicable to other enteropathogens BACKGROUND 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 . METHODS In a double-blind , placebo-controlled trial , 59 adults were r and omized to receive 50 microg 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 6x10(8 ) cfu 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 , vaccine 
    Output:
    