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: To provide optimum protection against classical and El Tor biotypes of Vibrio cholerae O1 , a single-dose , oral cholera vaccine was developed by combining two live , attenuated vaccine strains , CVD 103-HgR ( classical , Inaba ) and CVD 111 ( El Tor , Ogawa ) . The vaccines were formulated in a double-chamber sachet ; one chamber contained lyophilized bacteria , and the other contained buffer . In the first study , 23 U.S. adult volunteers received CVD 103-HgR at 10(8 ) CFU plus CVD 111 at 10(8 ) , 10(7 ) , or 10(6 ) CFU , CVD 111 alone at 10(7 ) CFU , or placebo . In the second study , 275 Peruvian adults were r and omized to receive CVD 103-HgR at 10(9 ) CFU plus CVD 111 at 10(9 ) or 10(8 ) CFU , CVD 111 alone at 10(9 ) CFU , CVD 103-HgR alone at 10(9 ) CFU , or placebo . Three of 15 U.S. volunteers who received CVD 111 at 10(7 ) or 10(8 ) CFU developed mild diarrhea , compared to none of 4 who received CVD 111 at 10(6 ) CFU and 1 of 4 who received placebo . Twelve ( 63 % ) of 19 vaccine recipients shed the El Tor vaccine strain . All but one volunteer developed significant Ogawa and Inaba vibriocidal antibody titers . Volunteers who received CVD 111 at 10(7 ) CFU had geometric mean Ogawa titers four to five times higher than those of volunteers who received the lower dose . In the second study , all dosage regimens were well tolerated in Peruvians . About 20 % of volunteers who received CVD 111 at the high dose excreted the El Tor organism , compared to 7 % in the low-dose group . CVD 111 was detected in the stools of two placebo recipients , neither of whom had symptoms or seroconverted . In all vaccine groups , 69 to 76 % developed fourfold rises in Inaba vibriocidal antibodies . Among those who received the bivalent vaccine , 53 to 75 % also developed significant rises in Ogawa vibriocidal antibodies . We conclude that it is feasible to produce a single-dose , oral bivalent vaccine that is safe and immunogenic against both biotypes ( El Tor and classical ) and both serotypes ( Inaba and Ogawa ) of cholera for population s in both developed and developing parts of the world BACKGROUND The human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine was immunogenic , generally well tolerated , and effective against HPV-16 or HPV-18 infections , and associated precancerous lesions in an event-triggered interim analysis of the phase III r and omised , double-blind , controlled PApilloma TRIal against Cancer In young Adults ( PATRICIA ) . We now assess the vaccine efficacy in the final event-driven analysis . METHODS Women ( 15 - 25 years ) were vaccinated at months 0 , 1 , and 6 . Analyses were done in the according-to- protocol cohort for efficacy ( ATP-E ; vaccine , n=8093 ; control , n=8069 ) , total vaccinated cohort ( TVC , included all women receiving at least one vaccine dose , regardless of their baseline HPV status ; represents the general population , including those who are sexually active ; vaccine , n=9319 ; control , n=9325 ) , and TVC-naive ( no evidence of oncogenic HPV infection at baseline ; represents women before sexual debut ; vaccine , n=5822 ; control , n=5819 ) . The primary endpoint was to assess vaccine efficacy against cervical intraepithelial neoplasia 2 + ( CIN2 + ) that was associated with HPV-16 or HPV-18 in women who were seronegative at baseline , and DNA negative at baseline and month 6 for the corresponding type ( ATP-E ) . This trial is registered with Clinical Trials.gov , number NCT00122681 . FINDINGS Mean follow-up was 34.9 months ( SD 6.4 ) after the third dose . Vaccine efficacy against CIN2 + associated with HPV-16/18 was 92.9 % ( 96.1 % CI 79.9 - 98.3 ) in the primary analysis and 98.1 % ( 88.4 - 100 ) in an analysis in which probable causality to HPV type was assigned in lesions infected with multiple oncogenic types ( ATP-E cohort ) . Vaccine efficacy against CIN2 + irrespective of HPV DNA in lesions was 30.4 % ( 16.4 - 42.1 ) in the TVC and 70.2 % ( 54.7 - 80.9 ) in the TVC-naive . Corresponding values against CIN3 + were 33.4 % ( 9.1 - 51.5 ) in the TVC and 87.0 % ( 54.9 - 97.7 ) in the TVC-naive . Vaccine efficacy against CIN2 + associated with 12 non-vaccine oncogenic types was 54.0 % ( 34.0 - 68.4 ; ATP-E ) . Individual cross-protection against CIN2 + associated with HPV-31 , HPV-33 , and HPV-45 was seen in the TVC . INTERPRETATION The HPV-16/18 AS04-adjuvanted vaccine showed high efficacy against CIN2 + associated with HPV-16/18 and non-vaccine oncogenic HPV types and substantial overall effect in cohorts that are relevant to universal mass vaccination and catch-up programmes . FUNDING GlaxoSmithKline Biologicals An oral rhesus-human rotavirus tetravalent ( RRV-TV ) vaccine ( 10(4 ) pfu of rhesus rotavirus [ type G3 ] and of 3 human-rhesus reassortants [ G1 , G2 , and G4 ] ) was evaluated in a field trial in Lima , Peru . At 2 , 3 , and 4 months of age , infants received either a dose of RRV-TV , an initial dose of vaccine followed by a dose of placebo at 3 and 4 months , or a dose of placebo .  Rotavirus-specific IgA responses were detected by ELISA in 75 % of the three-dose vaccine group , 59 % of the one-dose vaccine group ( P = .05 ) , and 24 % of the placebo group ( P < .001 ) : 64 % , 48 % , and 12 % of each group , respectively , had a neutralizing antibody response to at least 1 serotype . Both one and three doses of vaccine failed to induce a significant level of protection against rotavirus diarrhea ; however , they did provide some protection ( range , 35%-66 % ) against more severe rotavirus diarrhea , especially for episodes caused by type G1 Phase-III vaccine efficacy  trials typically employ individually r and omized design s intended to ensure that measurements of vaccine protective efficacy reflect only direct vaccine effects . As a result , decisions about introducing newly licensed vaccines into public health programmes often fail to consider the substantially greater protection that may occur when a vaccine is deployed in public health programmes , due to the combination of direct plus indirect vaccine protective effects . Vaccine total protection can be better evaluated with cluster r and omized trials . Such a design was considered to generate policy relevant data to accelerate the rationale introduction of the licensed typhoid fever Vi polysaccharide ( PS ) vaccine in Asia by the Diseases of the Most Impoverished ( DOMI ) typhoid fever programme . The DOMI 's programme multi-country study is one of the largest cluster r and omized vaccine trials ever mounted in Asia , which includes approximately 200,000 individuals . Its main objective is to determine the effectiveness of a licensed Vi PS vaccine .  The rationale and design of this study are discussed . Preliminary results are presented that determined the final planning of the trial before immunization . Important method ological and practical issues regarding vaccine cluster r and omized design s are illustrated Objectives An effective vaccine against cholera has been used for public health purpose s in Vietnam since the 1990s . This vaccine was reformulated to meet WHO requirements . We assessed the safety and immunogenicity of the reformulated bivalent ( Vibrio cholerae 01 and 0139 ) killed whole cell oral vaccine in a cholera endemic area in Kolkata , India . Design Double-blind , r and omized , placebo controlled trial Setting The trial was conducted in the clinical trial ward of the Infectious Diseases Hospital in Kolkata , India Participants The participants were 101 healthy adults ( males and non-pregnant females ) aged 18–40 years and 100 healthy children ( males and non-pregnant females ) aged 1–17 years . Interventions Participants were r and omized to receive either the bivalent killed whole cell oral cholera vaccine or placebo ( killed oral Escherichia coli K12 ) Outcome Measures For safety : proportion of subjects with adverse events during the duration of study participation . For immunogenicity : Proportion of subjects who had a ≥4-fold rise in serum vibriocidal antibody titers 14 days after the second dose of vaccine or placebo . Results Adverse reactions were observed with similar frequency among vaccine and placebo recipients in both age groups . Among adults 4 % of vaccine and 8 % of placebo recipients and among children 4 % of vaccine and 2 % of placebo recipients had at least one adverse event within 28 days of the first dose of the vaccine . Following immunization , 53 % of adult and 80 % of children vaccinees showed a ≥4 fold rise in serum V. cholerae O1 vibriocidal antibody titers . A less pronounced response to V. cholerae O139 vibriocidal antibody titers post-immunization was noted among vaccinees . Conclusions We found the vaccine to be safe and immunogenic in a cholera-endemic area in India . Trial Registration Clinical Trials.gov Objectives : The objectives were to evaluate the safety , reactogenicity , and allele-specific immunogenicity of the blood-stage malaria vaccine FMP1/AS02A in adults exposed to seasonal malaria and the impact of natural infection on vaccine-induced antibody levels . Design : We conducted a r and omized , double-blind , controlled phase I clinical trial . Setting : B and iagara , Mali , West Africa , is a rural town with intense seasonal transmission of Plasmodium falciparum malaria . Participants : Forty healthy , malaria-experienced Malian adults aged 18–55 y were enrolled . Interventions : The FMP1/AS02A malaria vaccine is a 42-kDa recombinant protein based on the carboxy-terminal end of merozoite surface protein-1 ( MSP-142 ) from the 3D7 clone of P. falciparum , adjuvanted with AS02A . The control vaccine was a killed rabies virus vaccine ( Imovax ) . Participants were r and omized to receive either FMP1/AS02A or rabies vaccine at 0 , 1 , and 2 mo and were followed for 1 y. Outcome Measures : Solicited and unsolicited adverse events and allele-specific antibody responses to recombinant MSP-142 and its subunits derived from P. falciparum strains homologous and heterologous to the 3D7 vaccine strain were measured . Results : Transient local pain and swelling were more common in the malaria vaccine group than in the control group ( 11/20 versus 3/20 and 10/20 versus 6/20 , respectively ) . MSP-142 antibody levels rose during the malaria transmission season in the control group , but were significantly higher in malaria vaccine recipients after the second immunization and remained higher after the third immunization relative both to baseline and to the control group . Immunization with the malaria vaccine was followed by significant increases in antibodies recognizing three diverse MSP-142 alleles and their subunits . Conclusions : FMP1/AS02A was well tolerated and highly immunogenic in adults exposed to intense seasonal malaria transmission and elicited immune responses to genetically diverse parasite clones . Anti-MSP-142 antibody levels followed a seasonal pattern that was significantly augmented and prolonged by the malaria vaccine Background One of the goals of this study was to learn the coverage , safety and logistics of a mass vaccination campaign against typhoid fever in children and adults using locally produced typhoid Vi polysaccharide ( PS ) and group A meningococcal PS vaccines in southern China . Methods The vaccination campaign targeted 118,588 persons in Hechi , Guangxi Province , aged between 5 to 60 years , in 2003 . The study area was divided into 107 geographic clusters , which were r 
    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: To provide optimum protection against classical and El Tor biotypes of Vibrio cholerae O1 , a single-dose , oral cholera vaccine was developed by combining two live , attenuated vaccine strains , CVD 103-HgR ( classical , Inaba ) and CVD 111 ( El Tor , Ogawa ) . The vaccines were formulated in a double-chamber sachet ; one chamber contained lyophilized bacteria , and the other contained buffer . In the first study , 23 U.S. adult volunteers received CVD 103-HgR at 10(8 ) CFU plus CVD 111 at 10(8 ) , 10(7 ) , or 10(6 ) CFU , CVD 111 alone at 10(7 ) CFU , or placebo . In the second study , 275 Peruvian adults were r and omized to receive CVD 103-HgR at 10(9 ) CFU plus CVD 111 at 10(9 ) or 10(8 ) CFU , CVD 111 alone at 10(9 ) CFU , CVD 103-HgR alone at 10(9 ) CFU , or placebo . Three of 15 U.S. volunteers who received CVD 111 at 10(7 ) or 10(8 ) CFU developed mild diarrhea , compared to none of 4 who received CVD 111 at 10(6 ) CFU and 1 of 4 who received placebo . Twelve ( 63 % ) of 19 vaccine recipients shed the El Tor vaccine strain . All but one volunteer developed significant Ogawa and Inaba vibriocidal antibody titers . Volunteers who received CVD 111 at 10(7 ) CFU had geometric mean Ogawa titers four to five times higher than those of volunteers who received the lower dose . In the second study , all dosage regimens were well tolerated in Peruvians . About 20 % of volunteers who received CVD 111 at the high dose excreted the El Tor organism , compared to 7 % in the low-dose group . CVD 111 was detected in the stools of two placebo recipients , neither of whom had symptoms or seroconverted . In all vaccine groups , 69 to 76 % developed fourfold rises in Inaba vibriocidal antibodies . Among those who received the bivalent vaccine , 53 to 75 % also developed significant rises in Ogawa vibriocidal antibodies . We conclude that it is feasible to produce a single-dose , oral bivalent vaccine that is safe and immunogenic against both biotypes ( El Tor and classical ) and both serotypes ( Inaba and Ogawa ) of cholera for population s in both developed and developing parts of the world BACKGROUND The human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine was immunogenic , generally well tolerated , and effective against HPV-16 or HPV-18 infections , and associated precancerous lesions in an event-triggered interim analysis of the phase III r and omised , double-blind , controlled PApilloma TRIal against Cancer In young Adults ( PATRICIA ) . We now assess the vaccine efficacy in the final event-driven analysis . METHODS Women ( 15 - 25 years ) were vaccinated at months 0 , 1 , and 6 . Analyses were done in the according-to- protocol cohort for efficacy ( ATP-E ; vaccine , n=8093 ; control , n=8069 ) , total vaccinated cohort ( TVC , included all women receiving at least one vaccine dose , regardless of their baseline HPV status ; represents the general population , including those who are sexually active ; vaccine , n=9319 ; control , n=9325 ) , and TVC-naive ( no evidence of oncogenic HPV infection at baseline ; represents women before sexual debut ; vaccine , n=5822 ; control , n=5819 ) . The primary endpoint was to assess vaccine efficacy against cervical intraepithelial neoplasia 2 + ( CIN2 + ) that was associated with HPV-16 or HPV-18 in women who were seronegative at baseline , and DNA negative at baseline and month 6 for the corresponding type ( ATP-E ) . This trial is registered with Clinical Trials.gov , number NCT00122681 . FINDINGS Mean follow-up was 34.9 months ( SD 6.4 ) after the third dose . Vaccine efficacy against CIN2 + associated with HPV-16/18 was 92.9 % ( 96.1 % CI 79.9 - 98.3 ) in the primary analysis and 98.1 % ( 88.4 - 100 ) in an analysis in which probable causality to HPV type was assigned in lesions infected with multiple oncogenic types ( ATP-E cohort ) . Vaccine efficacy against CIN2 + irrespective of HPV DNA in lesions was 30.4 % ( 16.4 - 42.1 ) in the TVC and 70.2 % ( 54.7 - 80.9 ) in the TVC-naive . Corresponding values against CIN3 + were 33.4 % ( 9.1 - 51.5 ) in the TVC and 87.0 % ( 54.9 - 97.7 ) in the TVC-naive . Vaccine efficacy against CIN2 + associated with 12 non-vaccine oncogenic types was 54.0 % ( 34.0 - 68.4 ; ATP-E ) . Individual cross-protection against CIN2 + associated with HPV-31 , HPV-33 , and HPV-45 was seen in the TVC . INTERPRETATION The HPV-16/18 AS04-adjuvanted vaccine showed high efficacy against CIN2 + associated with HPV-16/18 and non-vaccine oncogenic HPV types and substantial overall effect in cohorts that are relevant to universal mass vaccination and catch-up programmes . FUNDING GlaxoSmithKline Biologicals An oral rhesus-human rotavirus tetravalent ( RRV-TV ) vaccine ( 10(4 ) pfu of rhesus rotavirus [ type G3 ] and of 3 human-rhesus reassortants [ G1 , G2 , and G4 ] ) was evaluated in a field trial in Lima , Peru . At 2 , 3 , and 4 months of age , infants received either a dose of RRV-TV , an initial dose of vaccine followed by a dose of placebo at 3 and 4 months , or a dose of placebo .  Rotavirus-specific IgA responses were detected by ELISA in 75 % of the three-dose vaccine group , 59 % of the one-dose vaccine group ( P = .05 ) , and 24 % of the placebo group ( P < .001 ) : 64 % , 48 % , and 12 % of each group , respectively , had a neutralizing antibody response to at least 1 serotype . Both one and three doses of vaccine failed to induce a significant level of protection against rotavirus diarrhea ; however , they did provide some protection ( range , 35%-66 % ) against more severe rotavirus diarrhea , especially for episodes caused by type G1 Phase-III vaccine efficacy  trials typically employ individually r and omized design s intended to ensure that measurements of vaccine protective efficacy reflect only direct vaccine effects . As a result , decisions about introducing newly licensed vaccines into public health programmes often fail to consider the substantially greater protection that may occur when a vaccine is deployed in public health programmes , due to the combination of direct plus indirect vaccine protective effects . Vaccine total protection can be better evaluated with cluster r and omized trials . Such a design was considered to generate policy relevant data to accelerate the rationale introduction of the licensed typhoid fever Vi polysaccharide ( PS ) vaccine in Asia by the Diseases of the Most Impoverished ( DOMI ) typhoid fever programme . The DOMI 's programme multi-country study is one of the largest cluster r and omized vaccine trials ever mounted in Asia , which includes approximately 200,000 individuals . Its main objective is to determine the effectiveness of a licensed Vi PS vaccine .  The rationale and design of this study are discussed . Preliminary results are presented that determined the final planning of the trial before immunization . Important method ological and practical issues regarding vaccine cluster r and omized design s are illustrated Objectives An effective vaccine against cholera has been used for public health purpose s in Vietnam since the 1990s . This vaccine was reformulated to meet WHO requirements . We assessed the safety and immunogenicity of the reformulated bivalent ( Vibrio cholerae 01 and 0139 ) killed whole cell oral vaccine in a cholera endemic area in Kolkata , India . Design Double-blind , r and omized , placebo controlled trial Setting The trial was conducted in the clinical trial ward of the Infectious Diseases Hospital in Kolkata , India Participants The participants were 101 healthy adults ( males and non-pregnant females ) aged 18–40 years and 100 healthy children ( males and non-pregnant females ) aged 1–17 years . Interventions Participants were r and omized to receive either the bivalent killed whole cell oral cholera vaccine or placebo ( killed oral Escherichia coli K12 ) Outcome Measures For safety : proportion of subjects with adverse events during the duration of study participation . For immunogenicity : Proportion of subjects who had a ≥4-fold rise in serum vibriocidal antibody titers 14 days after the second dose of vaccine or placebo . Results Adverse reactions were observed with similar frequency among vaccine and placebo recipients in both age groups . Among adults 4 % of vaccine and 8 % of placebo recipients and among children 4 % of vaccine and 2 % of placebo recipients had at least one adverse event within 28 days of the first dose of the vaccine . Following immunization , 53 % of adult and 80 % of children vaccinees showed a ≥4 fold rise in serum V. cholerae O1 vibriocidal antibody titers . A less pronounced response to V. cholerae O139 vibriocidal antibody titers post-immunization was noted among vaccinees . Conclusions We found the vaccine to be safe and immunogenic in a cholera-endemic area in India . Trial Registration Clinical Trials.gov Objectives : The objectives were to evaluate the safety , reactogenicity , and allele-specific immunogenicity of the blood-stage malaria vaccine FMP1/AS02A in adults exposed to seasonal malaria and the impact of natural infection on vaccine-induced antibody levels . Design : We conducted a r and omized , double-blind , controlled phase I clinical trial . Setting : B and iagara , Mali , West Africa , is a rural town with intense seasonal transmission of Plasmodium falciparum malaria . Participants : Forty healthy , malaria-experienced Malian adults aged 18–55 y were enrolled . Interventions : The FMP1/AS02A malaria vaccine is a 42-kDa recombinant protein based on the carboxy-terminal end of merozoite surface protein-1 ( MSP-142 ) from the 3D7 clone of P. falciparum , adjuvanted with AS02A . The control vaccine was a killed rabies virus vaccine ( Imovax ) . Participants were r and omized to receive either FMP1/AS02A or rabies vaccine at 0 , 1 , and 2 mo and were followed for 1 y. Outcome Measures : Solicited and unsolicited adverse events and allele-specific antibody responses to recombinant MSP-142 and its subunits derived from P. falciparum strains homologous and heterologous to the 3D7 vaccine strain were measured . Results : Transient local pain and swelling were more common in the malaria vaccine group than in the control group ( 11/20 versus 3/20 and 10/20 versus 6/20 , respectively ) . MSP-142 antibody levels rose during the malaria transmission season in the control group , but were significantly higher in malaria vaccine recipients after the second immunization and remained higher after the third immunization relative both to baseline and to the control group . Immunization with the malaria vaccine was followed by significant increases in antibodies recognizing three diverse MSP-142 alleles and their subunits . Conclusions : FMP1/AS02A was well tolerated and highly immunogenic in adults exposed to intense seasonal malaria transmission and elicited immune responses to genetically diverse parasite clones . Anti-MSP-142 antibody levels followed a seasonal pattern that was significantly augmented and prolonged by the malaria vaccine Background One of the goals of this study was to learn the coverage , safety and logistics of a mass vaccination campaign against typhoid fever in children and adults using locally produced typhoid Vi polysaccharide ( PS ) and group A meningococcal PS vaccines in southern China . Methods The vaccination campaign targeted 118,588 persons in Hechi , Guangxi Province , aged between 5 to 60 years , in 2003 . The study area was divided into 107 geographic clusters , which were r 
    Output:
    