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: The live , auxotrophic Shigella flexneri vaccine strain SFL124 was given in a single dose of 10(7 ) , 10(8 ) or 10(9 ) colony forming units ( cfu ) , respectively , to each of three groups of 10 Vietnamese children aged 9 - 14 years . The vaccine was well tolerated by all the children without any severe side effects such as diarrhoea or fever being observed . Mild symptoms were reported by five children . Only five children were found by culture to excrete SFL124 but , by PCR , 28 of 30 children were found to excrete the vaccine strain for up to 5 days ( mean 2.8 days ) with insignificant differences among the groups . Local mucosal immune responses and antibody secreting cell ( ASC ) responses to S. flexneri lipopolysaccharide ( LPS ) and invasion plasmid-coded antigens ( Ipa ) were elicited in the children in a dose-dependent manner . Doses of 10(9 ) cfu induced most prominent responses , followed by those of 10(8 ) and 10(7 ) cfu . The sIgA responses were the highest whereas the ASC were modest . High titres of serum antibodies to Shigella LPS and Ipa were found in all the children before ingestion of the vaccine which elicited increases in serum antibody titres in only a few of them . The immune response patterns seen indicate a booster rather than a primary response and may be a consequence of the endemic nature of shigellosis in Vietnam In double-blind trials in Bangladesh , 88 adults , and 79 children ( 8 - 10 years ) were r and omized to receive either a single oral dose of 1 × 10(4 ) , 1 × 10(5 ) or 1 × 10(6)CFU of SC602 ( a live , attenuated Shigella flexneri 2a strain vaccine ) or placebo . In the adult outpatient 1 × 10(6 ) CFU group , severe joint pain and body aches were reported by one and two vaccinees respectively . In the adult inpatient trial , SC602 was isolated from 3 volunteers , pre-vaccination antibody titers were high , and fourfold increases in serum IgG anti-LPS responses were observed in 2 of 5 subjects of the 1 × 10(6)CFU group . None of the volunteers developed diarrhea . Overall , SC602 was found to be associated with minimal vaccine shedding , minimal reactogenicity , no transmission risk , and low immune stimulation 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 In the summer of 2005 , we interviewed 996 r and omly selected respondents in Beira , Mozambique concerning their willingness and ability to pay for cholera vaccine for themselves and for other household members . Respondents were told that two doses of the vaccine would be required 2 weeks apart , and that the cholera vaccine would offer excellent protection against infection for the first year following vaccination , and some protection during the second and third year after a person is vaccinated . This research was carried out in order to learn more about private dem and for vaccines in a cholera-endemic area . We asked two types of valuation questions : ( 1 ) a discrete-price offer for a vaccine that could be purchased for household members and ( 2 ) a payment card design ed to assess uncertainty in the respondent 's dem and for a vaccine for self-protection . We estimate average household willingness to pay ( WTP ) for cholera vaccines in Beira to be 2005 US$ 8.45 . This estimate of household WTP represents the perceived private economic benefits to a household -- six persons on average -- of giving all members free cholera vaccines Recombinant A-B+ Vibrio cholerae O1 strain CVD 103-HgR is a safe , highly immunogenic , single-dose live oral vaccine in adults in industrialized countries .  Safety , excretion , immunogenicity , vaccine transmissibility , and environmental introduction of CVD 103-HgR were investigated among 24- to 59-month-old children in Jakarta . In 81 households , 1 child was r and omly allocated a single dose of vaccine ( 5 x 10(9 ) cfu ) and another , placebo . Additionally , 139 unpaired children were r and omly allocated vaccine or placebo .  During 9 days of follow-up , diarrhea or vomiting did not occur more often among vaccines than controls . Vaccine was minimally excreted and was isolated from no controls and from 1 ( 0.6 % ) of 177 unvaccinated family contacts . A 4-fold or higher rise in serum vibriocidal antibody was observed in 75 % of vaccines ( 10-fold rise in geometric mean titer over baseline ) . Of 135 paired placebo recipients or household contacts , 5 had vibriocidal seroconversions . Moore swabs placed in sewers and latrines near 97 households failed to detect vaccine . These observations pave the way for a large-scale field trial of efficacy 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 Background Killed oral cholera vaccines ( OCVs ) have been licensed for use in developing countries , but protection conferred by licensed OCVs beyond two years of follow-up has not been demonstrated in r and omized , clinical trials . Methods /Principal Findings We conducted a cluster-r and omized , placebo-controlled trial of a two-dose regimen of a low-cost killed whole cell OCV in residents 1 year of age and older living in 3,933 clusters in Kolkata , India . The primary endpoint was culture-proven Vibrio cholerae O1 diarrhea episodes severe enough to require treatment in a health care facility . Of the 66,900 fully dosed individuals ( 31,932 vaccinees and 34,968 placebo recipients ) , 38 vaccinees and 128 placebo-recipients developed cholera during three years of follow-up ( protective efficacy 66 % ; one-sided 95%CI lower bound = 53 % , p<0.001 ) . Vaccine protection during the third year of follow-up was 65 % ( one-sided 95%CI lower bound = 44 % , p<0.001 ) . Significant protection was evident in the second year of follow-up in children vaccinated at ages 1–4 years and in the third year in older age groups . Conclusions / Significance The killed whole-cell OCV conferred significant protection that was evident in the second year of follow-up in young children and was sustained for at least three years in older age groups . Continued follow-up will be important to establish the vaccine 's duration of protection . Trial Registration Clinical Trials.gov NCT00289224 In January and February 1992 , an assessment was conducted of the safety and immunogenicity of two doses of a new oral cholera vaccine prepared from the recombinant B subunit of the toxin and from killed whole cells ( rBS/WC ) in 1,165 individuals between the ages of 12 months and 64 years in Barranquilla , Colombia . This was a r and omized , double-blind placebo-controlled study . Participants received two doses of either the vaccine or a placebo ( killed Escherichia coli K12 ) over a two-week interval . Few symptoms were detected during the three days following administration of the initial dose and even fewer following the second . Sera obtained upon administration of the first dose and two weeks after administration of the second were tested for Vibrio cholerae 01 Inaba vibriocidal antibodies and antitoxins . Geometric mean titers ( GMT ) of vibriocidal antibodies were found to increase two-fold in subjects receiving the vaccine . In the paired sample s taken from vaccinated subjects , two-fold or greater increases were observed in 44 % and four-fold or greater increases were observed in 34 % , as compared to similar increases in 9.2 % and 2.2 % of the sera taken from those receiving the placebo ( P < 0.05 ) . The GMTs of IgG and IgA antitoxins , as determined by ELISA , increased by factors of 4 and 3.2 , respectively , in those receiving the vaccine , as compared to factors of 1.1 and 1.1 in those given the placebo ( P < 0.001 for IgG , P < 0.01 for IgA ) . Approximately 80 % of the paired sample s from the vaccinated group showed an increase of both IgG and IgA antitoxins > or = 1.5 , as compared to only about 20 % of those in the placebo group ( P < 0.000001 ) . Belonging to the O blood group did not significantly affect the immune response . Children under age four tended to show a weaker vibriocidal antibody response and a stronger antitoxin response than older subjects . The two doses of oral vaccine were found to be safe and without attributable side-effects . The vibriocidal antibody and antitoxin responses were similar to those obtained previously with the conventional oral killed whole cell B subunit cholera vaccine To evaluate the probiotic , Bifidobacterium breve strain Yakult ( BBG-01 ) , for safety and enhancement of immunogenicity in an oral inactivated cholera vaccine , a r and omized double-blind placebo-controlled study was performed . Bangladeshi children under 5-year-old received BBG-01 or placebo for 4 weeks with two doses of oral cholera vaccine .  Serum 
    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: The live , auxotrophic Shigella flexneri vaccine strain SFL124 was given in a single dose of 10(7 ) , 10(8 ) or 10(9 ) colony forming units ( cfu ) , respectively , to each of three groups of 10 Vietnamese children aged 9 - 14 years . The vaccine was well tolerated by all the children without any severe side effects such as diarrhoea or fever being observed . Mild symptoms were reported by five children . Only five children were found by culture to excrete SFL124 but , by PCR , 28 of 30 children were found to excrete the vaccine strain for up to 5 days ( mean 2.8 days ) with insignificant differences among the groups . Local mucosal immune responses and antibody secreting cell ( ASC ) responses to S. flexneri lipopolysaccharide ( LPS ) and invasion plasmid-coded antigens ( Ipa ) were elicited in the children in a dose-dependent manner . Doses of 10(9 ) cfu induced most prominent responses , followed by those of 10(8 ) and 10(7 ) cfu . The sIgA responses were the highest whereas the ASC were modest . High titres of serum antibodies to Shigella LPS and Ipa were found in all the children before ingestion of the vaccine which elicited increases in serum antibody titres in only a few of them . The immune response patterns seen indicate a booster rather than a primary response and may be a consequence of the endemic nature of shigellosis in Vietnam In double-blind trials in Bangladesh , 88 adults , and 79 children ( 8 - 10 years ) were r and omized to receive either a single oral dose of 1 × 10(4 ) , 1 × 10(5 ) or 1 × 10(6)CFU of SC602 ( a live , attenuated Shigella flexneri 2a strain vaccine ) or placebo . In the adult outpatient 1 × 10(6 ) CFU group , severe joint pain and body aches were reported by one and two vaccinees respectively . In the adult inpatient trial , SC602 was isolated from 3 volunteers , pre-vaccination antibody titers were high , and fourfold increases in serum IgG anti-LPS responses were observed in 2 of 5 subjects of the 1 × 10(6)CFU group . None of the volunteers developed diarrhea . Overall , SC602 was found to be associated with minimal vaccine shedding , minimal reactogenicity , no transmission risk , and low immune stimulation 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 In the summer of 2005 , we interviewed 996 r and omly selected respondents in Beira , Mozambique concerning their willingness and ability to pay for cholera vaccine for themselves and for other household members . Respondents were told that two doses of the vaccine would be required 2 weeks apart , and that the cholera vaccine would offer excellent protection against infection for the first year following vaccination , and some protection during the second and third year after a person is vaccinated . This research was carried out in order to learn more about private dem and for vaccines in a cholera-endemic area . We asked two types of valuation questions : ( 1 ) a discrete-price offer for a vaccine that could be purchased for household members and ( 2 ) a payment card design ed to assess uncertainty in the respondent 's dem and for a vaccine for self-protection . We estimate average household willingness to pay ( WTP ) for cholera vaccines in Beira to be 2005 US$ 8.45 . This estimate of household WTP represents the perceived private economic benefits to a household -- six persons on average -- of giving all members free cholera vaccines Recombinant A-B+ Vibrio cholerae O1 strain CVD 103-HgR is a safe , highly immunogenic , single-dose live oral vaccine in adults in industrialized countries .  Safety , excretion , immunogenicity , vaccine transmissibility , and environmental introduction of CVD 103-HgR were investigated among 24- to 59-month-old children in Jakarta . In 81 households , 1 child was r and omly allocated a single dose of vaccine ( 5 x 10(9 ) cfu ) and another , placebo . Additionally , 139 unpaired children were r and omly allocated vaccine or placebo .  During 9 days of follow-up , diarrhea or vomiting did not occur more often among vaccines than controls . Vaccine was minimally excreted and was isolated from no controls and from 1 ( 0.6 % ) of 177 unvaccinated family contacts . A 4-fold or higher rise in serum vibriocidal antibody was observed in 75 % of vaccines ( 10-fold rise in geometric mean titer over baseline ) . Of 135 paired placebo recipients or household contacts , 5 had vibriocidal seroconversions . Moore swabs placed in sewers and latrines near 97 households failed to detect vaccine . These observations pave the way for a large-scale field trial of efficacy 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 Background Killed oral cholera vaccines ( OCVs ) have been licensed for use in developing countries , but protection conferred by licensed OCVs beyond two years of follow-up has not been demonstrated in r and omized , clinical trials . Methods /Principal Findings We conducted a cluster-r and omized , placebo-controlled trial of a two-dose regimen of a low-cost killed whole cell OCV in residents 1 year of age and older living in 3,933 clusters in Kolkata , India . The primary endpoint was culture-proven Vibrio cholerae O1 diarrhea episodes severe enough to require treatment in a health care facility . Of the 66,900 fully dosed individuals ( 31,932 vaccinees and 34,968 placebo recipients ) , 38 vaccinees and 128 placebo-recipients developed cholera during three years of follow-up ( protective efficacy 66 % ; one-sided 95%CI lower bound = 53 % , p<0.001 ) . Vaccine protection during the third year of follow-up was 65 % ( one-sided 95%CI lower bound = 44 % , p<0.001 ) . Significant protection was evident in the second year of follow-up in children vaccinated at ages 1–4 years and in the third year in older age groups . Conclusions / Significance The killed whole-cell OCV conferred significant protection that was evident in the second year of follow-up in young children and was sustained for at least three years in older age groups . Continued follow-up will be important to establish the vaccine 's duration of protection . Trial Registration Clinical Trials.gov NCT00289224 In January and February 1992 , an assessment was conducted of the safety and immunogenicity of two doses of a new oral cholera vaccine prepared from the recombinant B subunit of the toxin and from killed whole cells ( rBS/WC ) in 1,165 individuals between the ages of 12 months and 64 years in Barranquilla , Colombia . This was a r and omized , double-blind placebo-controlled study . Participants received two doses of either the vaccine or a placebo ( killed Escherichia coli K12 ) over a two-week interval . Few symptoms were detected during the three days following administration of the initial dose and even fewer following the second . Sera obtained upon administration of the first dose and two weeks after administration of the second were tested for Vibrio cholerae 01 Inaba vibriocidal antibodies and antitoxins . Geometric mean titers ( GMT ) of vibriocidal antibodies were found to increase two-fold in subjects receiving the vaccine . In the paired sample s taken from vaccinated subjects , two-fold or greater increases were observed in 44 % and four-fold or greater increases were observed in 34 % , as compared to similar increases in 9.2 % and 2.2 % of the sera taken from those receiving the placebo ( P < 0.05 ) . The GMTs of IgG and IgA antitoxins , as determined by ELISA , increased by factors of 4 and 3.2 , respectively , in those receiving the vaccine , as compared to factors of 1.1 and 1.1 in those given the placebo ( P < 0.001 for IgG , P < 0.01 for IgA ) . Approximately 80 % of the paired sample s from the vaccinated group showed an increase of both IgG and IgA antitoxins > or = 1.5 , as compared to only about 20 % of those in the placebo group ( P < 0.000001 ) . Belonging to the O blood group did not significantly affect the immune response . Children under age four tended to show a weaker vibriocidal antibody response and a stronger antitoxin response than older subjects . The two doses of oral vaccine were found to be safe and without attributable side-effects . The vibriocidal antibody and antitoxin responses were similar to those obtained previously with the conventional oral killed whole cell B subunit cholera vaccine To evaluate the probiotic , Bifidobacterium breve strain Yakult ( BBG-01 ) , for safety and enhancement of immunogenicity in an oral inactivated cholera vaccine , a r and omized double-blind placebo-controlled study was performed . Bangladeshi children under 5-year-old received BBG-01 or placebo for 4 weeks with two doses of oral cholera vaccine .  Serum 
    Output:
    