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: A meningococcal group B ( 15:P1.3 ) outer membrane protein vaccine was tested for efficacy in a r and omized , double-blind controlled study in Iquique , Chile . A total of 40 811 volunteers , ages 1 - 21 years , enrolled in the study . Volunteers received two doses of vaccine six weeks apart by jet injector . Both the experimental vaccine and the control vaccine ( Menomune , A , C , Y and W135 meningococcal polysaccharide vaccine ) were well tolerated with minor side-effects . Active surveillance for suspected cases of meningococcal disease was conducted for 20 months in Iquique . Eighteen cases of group B meningococcal disease were confirmed during the 20 months . Efficacy was estimated to be 51 % ( p = 0.11 ) for all ages combined . In children aged 1 - 4 no protection was evident , but in volunteers aged 5 - 21 vaccine efficacy was 70 % ( p = 0.045 ) . The IgG antibody response by ELISA was characterized by a large booster effect after the second dose , followed by a substantial drop in antibody levels by 6 months . The youngest children had the highest responses . The bactericidal antibody response , on the other h and , was characterized by the lack of a significant booster response , higher responses in the older children , and an increase in the geometric mean titer in the later months of the study in the older children Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more BACKGROUND Outer-membrane-vesicle vaccines for meningococcal B outbreaks are complex and time consuming to develop . We studied the use of already available vaccine to control an outbreak caused by a genetically close strain . METHODS From 2006 to 2009 , all individuals younger than 20 years living in the region of Norm and y , France , in which an outbreak caused by a B:14:P1.7,16 strain occurred , were eligible to receive MenBvac  , a  Norwegian vaccine  design ed 20 years earlier against a strain sharing the same serosubtype ( B:15:P1.7,16 ) . The immunogenicity ( in a r and omly selected cohort of 400 children aged 1 - 5 years ) , safety , and epidemiological effect of the vaccination were assessed . FINDINGS 26,014 individuals were eligible to receive the vaccine . Shortage of vaccine production prompted start of the campaign in the highest incidence groups ( 1 - 5 years ) . 16,709 ( 64 % ) received a complete vaccination schedule of whom 13,589 ( 81 % ) received a 2 + 1 dose schedule ( week 0 , week 6 , and month 8) . At 6 weeks after the third dose , of 235 vaccinees for whom sample s were available , 206 ( 88 % ) had a seroresponse , and 108 ( 56 % ) of 193 had a seroresponse at 15 months . These results were similar to those described for tailor-made vaccines and their homologous strain . Only previously described adverse effects occurred . The incidence of B:14:P1.7,16 cases decreased significantly in the vaccine targeted population after the primary vaccination period ( from 31·6 per 100,000 to 5·9 per 100,000 ; p=0·001 ) . INTERPRETATION The ready-to-wear approach is reliable if epidemic and vaccine strains are genetically close . Other meningococcal B clonal outbreaks might benefit from this strategy ; and previously described outer-membrane-vesicle vaccines can be effective against various strains . FUNDING French Ministry of Health The effectiveness of a new  group B strain-specific meningococcal vaccine referred to as " MeNZB , " developed by Chiron Vaccines ( Siena , Italy ) in collaboration with the Norwegian Institute of Public Health , was assessed in a prospect i ve observational study following a nationwide vaccination program in New Zeal and . The  vaccination program began in July 2004 , and the study uses data from January 2001 to June 2006 . A generalized estimating equation model was used to estimate vaccine effectiveness that included potential confounding variables , such as disease progression over time , age , ethnicity , socioeconomic status , seasonality , and geographic region . The model provides strong statistical evidence for a vaccine effect ( p < 0.0001 ) , with estimated disease rates 3.7 times higher in the unvaccinated group than in the vaccinated group ( 95 % confidence interval : 2.1 , 6.8 ) and a vaccine effectiveness of 73 % ( 95 % confidence interval : 52 , 85 ) . An estimated 54 epidemic strain meningococcal cases were prevented in the 2 years since the vaccination program began ( 95 % confidence interval assuming a fixed population size : 22 , 115 ) . In a sensitivity analysis , these estimates proved to be robust to modeling assumptions , including population estimates , estimates of the numbers vaccinated , effects of partial vaccination , and temporal autocorrelation Clinical studies have been conducted in New Zeal and evaluating the safety and immunogenicity of an outer membrane vesicle ( OMV ) vaccine , MeNZB , developed to control epidemic disease caused by group B meningococci , subtype P1.7b,4 . MeNZB , administered in a three-dose regimen , was well tolerated and induced a seroresponse , defined as a four-fold rise ( > or = titre 8) in serum bactericidal antibodies against the vaccine strain 4 - 6 weeks after the third vaccination , in 96 % ( 95 % confidence interval ( CI ) : 79 - 100 % ) of adults , 76 % ( 95 % CI : 72 - 80 % ) of children , 75 % ( 95 % CI : 69 - 80 % ) of toddlers and 74 % ( 95 % CI : 67 - 80 % ) of infants receiving MeNZB . In conclusion , these findings suggest that MeNZB is safe and is likely to confer protection against systemic group B meningococcal disease caused by the epidemic strain Since 1986 , serogroup B Neisseria meningitidis has caused approximately 80 % of the meningococcal disease in Brazil . In 1988 , an epidemic caused by N. meningitidis B:4:P1.15 was recognized in the greater São Paulo area of Brazil . The São Paulo state government decided to vaccinate children from 3 to 83 months of age with a vaccine consisting of serotype 4 outer membrane protein and group C meningococcal polysaccharide that was produced in Cuba . About 2.7 million children were vaccinated during two immunization campaigns conducted in 1989 and 1990 . Because of this , a case-control study was design ed to determine vaccine efficacy against group B meningococcal disease . The purpose of our study was to compare the antibody response with the protection from disease estimated from the case-control study . We measured the immune responses of vaccinees by enzyme-linked immunosorbent assay ( ELISA ) , immunoblot , and bactericidal assay . The development of bactericidal antibodies was age dependent and in good agreement with the results of the case-control study . Only 40 % of vaccinees showed fourfold or greater increases in bactericidal antibody titers after vaccination . A poor correlation between antibody levels detected by ELISA and those by bactericidal assay was found . Immunoblot analysis showed that about 50 % of the serum sample s with bactericidal titers higher than 1:4 were reactive with class 1 outer membrane protein . We conclude that the bactericidal assay is a good , laboratory-based , functional assay for the study of vaccine immunogenicity and that an effective solution to group B meningococcal disease remains to be demonstrated For evaluation of serum bactericidal activity ( SBA ) as surrogate for the efficacy of outer membrane vesicle ( OMV ) vaccines against Neisseria meningitidis serogroup B disease , we have reanalyzed data from a r and omized double blind placebo-controlled efficacy trial involving 172000 secondary school students ( aged 13 - 14 years ) in Norway ( 1988 - 1991 ) . A cohort of the efficacy trial consisting of 880 individuals was selected for immunogenicity studies . An efficacy of 87 % was calculated for a 10-month observation period . However , after an observation period of 29 months , the estimated efficacy against group B disease induced by vaccination was 57 % . The immunogenicity study showed that the SBA geometric mean titer ( GMT ) for the vaccinees was 2.4 before vaccination and 19.0 six weeks after the second vaccine dose . One year after vaccination the GMT was reduced to 2.8 . A separate three-dose study with 304 adolescents showed that with a third dose at 10 months after the second dose ( i.e. when cases of disease started to appear ) a strong booster response was induced . Ten months after the second dose the SBA was reduced to near pre-immunization level . Following the third dose the SBA geometric mean titer of 2.7 increased to 62.3 . One year after the third dose , the GMT was markedly higher than 6 weeks after the second dose ( 12.6 versus 8.8 ) . Thus , protection after vaccination corresponds with the level of SBA . In order to reach lasting protective levels of SBA in a population , three vaccine doses are probably required . Measurements of SBA are likely to be useful for evaluating various upcoming formulations and improvements of immunization regimens for OMV vaccines Background : New Zeal and has experienced an epidemic of Neisseria meningitidis dominated by strain B:4:P1.7b,4 since 1991 . Children younger than 5 years are at highest risk . Previous serogroup B outer membrane vesicle ( OMV ) strain specific vaccines have shown variable efficacy in this age group . Objective : To evaluate the immunogenicity , reactogenicity and safety in 16–24-month-old children of an OMV vaccine  developed against the New Zeal and epidemic strain . Methods : Children ( 332 ) aged 16–24 months were r and omized to receive the New Zeal and c and i date vaccine made using strain NZ98/254 ( B:4:P1.7b,4 ) or the Norwegian parent vaccine made using strain 44/76 ( B:15:P1.7,16 ) . Vaccines ( 25 μg/dose ) were administered at 0 , 6 and 12 weeks in this observer-blind trial . Immune response was measured by serum bactericidal assay and enzyme-linked immunosorbent assay . Sero-response was defined as a 4-fold or greater rise in serum bactericidal antibody titer compared with baseline , with titers < 1:4 required to increase to ≥1:8 to be considered a sero-response . Local and systemic reactions were monitored for 7 days after vaccination . Results : Sero-response against NZ98/254 was achieved after 3 doses in 75 % ( 95 % CI : 69–80 % ) receiving the New Zeal and c and i date vaccine by both intention to treat ( ITT ) and per protocol ( PP ) analyses . In Norwegian parent vaccinees this was seen in 3 % ( 0–12 % ) ( ITT ) and 4 % ( 0–13 % ) ( PP ) . Vaccines were well tolerated with no vaccine-related serious adverse events . Conclusion : The New Zeal and c and i date vaccine administered to these 16–24-month-old children in 3 doses was safe and elicited a promising immune response against the c and i date vaccine strain NZ98/254 ( N. meningitidis B:4:P1.7b,4 ) contributing to vaccine licensure for this age group BACKGROUND The serogroup B meningococcus is responsible for the majority of cases of meningococcal disease in temperate countries . Infants and young children < 2 years of age are at greatest risk of disease . This study assessed the immunogenicity in infants of a serogroup B meningococcal outer membrane protein vaccine  that has been used extensively in disease outbreaks in Cuba and several Latin American countries and shown to be efficacious in teenagers . METHOD One hundred five healthy infants entering the routine vaccination schedule in Havana , Cuba , were given either 2 or 3 doses of the serogroup B meningococcal vaccine VA-MENGOC-BC at 3.5 , 5.5 and 7.5 months of age . Immune response pre- and postvaccination was determined by the conventional serum bactericidal assay ( SBA ) , a more sensitive novel whole blood bactericidal assay ( WBA ) and immunoglobulin ELISA . RESULTS In 52 and 46 % of infants > 50 % killing of the vaccine serogroup B strain ( B:4:P1.19,15 ) and serogroup C strain 
    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: A meningococcal group B ( 15:P1.3 ) outer membrane protein vaccine was tested for efficacy in a r and omized , double-blind controlled study in Iquique , Chile . A total of 40 811 volunteers , ages 1 - 21 years , enrolled in the study . Volunteers received two doses of vaccine six weeks apart by jet injector . Both the experimental vaccine and the control vaccine ( Menomune , A , C , Y and W135 meningococcal polysaccharide vaccine ) were well tolerated with minor side-effects . Active surveillance for suspected cases of meningococcal disease was conducted for 20 months in Iquique . Eighteen cases of group B meningococcal disease were confirmed during the 20 months . Efficacy was estimated to be 51 % ( p = 0.11 ) for all ages combined . In children aged 1 - 4 no protection was evident , but in volunteers aged 5 - 21 vaccine efficacy was 70 % ( p = 0.045 ) . The IgG antibody response by ELISA was characterized by a large booster effect after the second dose , followed by a substantial drop in antibody levels by 6 months . The youngest children had the highest responses . The bactericidal antibody response , on the other h and , was characterized by the lack of a significant booster response , higher responses in the older children , and an increase in the geometric mean titer in the later months of the study in the older children Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more BACKGROUND Outer-membrane-vesicle vaccines for meningococcal B outbreaks are complex and time consuming to develop . We studied the use of already available vaccine to control an outbreak caused by a genetically close strain . METHODS From 2006 to 2009 , all individuals younger than 20 years living in the region of Norm and y , France , in which an outbreak caused by a B:14:P1.7,16 strain occurred , were eligible to receive MenBvac  , a  Norwegian vaccine  design ed 20 years earlier against a strain sharing the same serosubtype ( B:15:P1.7,16 ) . The immunogenicity ( in a r and omly selected cohort of 400 children aged 1 - 5 years ) , safety , and epidemiological effect of the vaccination were assessed . FINDINGS 26,014 individuals were eligible to receive the vaccine . Shortage of vaccine production prompted start of the campaign in the highest incidence groups ( 1 - 5 years ) . 16,709 ( 64 % ) received a complete vaccination schedule of whom 13,589 ( 81 % ) received a 2 + 1 dose schedule ( week 0 , week 6 , and month 8) . At 6 weeks after the third dose , of 235 vaccinees for whom sample s were available , 206 ( 88 % ) had a seroresponse , and 108 ( 56 % ) of 193 had a seroresponse at 15 months . These results were similar to those described for tailor-made vaccines and their homologous strain . Only previously described adverse effects occurred . The incidence of B:14:P1.7,16 cases decreased significantly in the vaccine targeted population after the primary vaccination period ( from 31·6 per 100,000 to 5·9 per 100,000 ; p=0·001 ) . INTERPRETATION The ready-to-wear approach is reliable if epidemic and vaccine strains are genetically close . Other meningococcal B clonal outbreaks might benefit from this strategy ; and previously described outer-membrane-vesicle vaccines can be effective against various strains . FUNDING French Ministry of Health The effectiveness of a new  group B strain-specific meningococcal vaccine referred to as " MeNZB , " developed by Chiron Vaccines ( Siena , Italy ) in collaboration with the Norwegian Institute of Public Health , was assessed in a prospect i ve observational study following a nationwide vaccination program in New Zeal and . The  vaccination program began in July 2004 , and the study uses data from January 2001 to June 2006 . A generalized estimating equation model was used to estimate vaccine effectiveness that included potential confounding variables , such as disease progression over time , age , ethnicity , socioeconomic status , seasonality , and geographic region . The model provides strong statistical evidence for a vaccine effect ( p < 0.0001 ) , with estimated disease rates 3.7 times higher in the unvaccinated group than in the vaccinated group ( 95 % confidence interval : 2.1 , 6.8 ) and a vaccine effectiveness of 73 % ( 95 % confidence interval : 52 , 85 ) . An estimated 54 epidemic strain meningococcal cases were prevented in the 2 years since the vaccination program began ( 95 % confidence interval assuming a fixed population size : 22 , 115 ) . In a sensitivity analysis , these estimates proved to be robust to modeling assumptions , including population estimates , estimates of the numbers vaccinated , effects of partial vaccination , and temporal autocorrelation Clinical studies have been conducted in New Zeal and evaluating the safety and immunogenicity of an outer membrane vesicle ( OMV ) vaccine , MeNZB , developed to control epidemic disease caused by group B meningococci , subtype P1.7b,4 . MeNZB , administered in a three-dose regimen , was well tolerated and induced a seroresponse , defined as a four-fold rise ( > or = titre 8) in serum bactericidal antibodies against the vaccine strain 4 - 6 weeks after the third vaccination , in 96 % ( 95 % confidence interval ( CI ) : 79 - 100 % ) of adults , 76 % ( 95 % CI : 72 - 80 % ) of children , 75 % ( 95 % CI : 69 - 80 % ) of toddlers and 74 % ( 95 % CI : 67 - 80 % ) of infants receiving MeNZB . In conclusion , these findings suggest that MeNZB is safe and is likely to confer protection against systemic group B meningococcal disease caused by the epidemic strain Since 1986 , serogroup B Neisseria meningitidis has caused approximately 80 % of the meningococcal disease in Brazil . In 1988 , an epidemic caused by N. meningitidis B:4:P1.15 was recognized in the greater São Paulo area of Brazil . The São Paulo state government decided to vaccinate children from 3 to 83 months of age with a vaccine consisting of serotype 4 outer membrane protein and group C meningococcal polysaccharide that was produced in Cuba . About 2.7 million children were vaccinated during two immunization campaigns conducted in 1989 and 1990 . Because of this , a case-control study was design ed to determine vaccine efficacy against group B meningococcal disease . The purpose of our study was to compare the antibody response with the protection from disease estimated from the case-control study . We measured the immune responses of vaccinees by enzyme-linked immunosorbent assay ( ELISA ) , immunoblot , and bactericidal assay . The development of bactericidal antibodies was age dependent and in good agreement with the results of the case-control study . Only 40 % of vaccinees showed fourfold or greater increases in bactericidal antibody titers after vaccination . A poor correlation between antibody levels detected by ELISA and those by bactericidal assay was found . Immunoblot analysis showed that about 50 % of the serum sample s with bactericidal titers higher than 1:4 were reactive with class 1 outer membrane protein . We conclude that the bactericidal assay is a good , laboratory-based , functional assay for the study of vaccine immunogenicity and that an effective solution to group B meningococcal disease remains to be demonstrated For evaluation of serum bactericidal activity ( SBA ) as surrogate for the efficacy of outer membrane vesicle ( OMV ) vaccines against Neisseria meningitidis serogroup B disease , we have reanalyzed data from a r and omized double blind placebo-controlled efficacy trial involving 172000 secondary school students ( aged 13 - 14 years ) in Norway ( 1988 - 1991 ) . A cohort of the efficacy trial consisting of 880 individuals was selected for immunogenicity studies . An efficacy of 87 % was calculated for a 10-month observation period . However , after an observation period of 29 months , the estimated efficacy against group B disease induced by vaccination was 57 % . The immunogenicity study showed that the SBA geometric mean titer ( GMT ) for the vaccinees was 2.4 before vaccination and 19.0 six weeks after the second vaccine dose . One year after vaccination the GMT was reduced to 2.8 . A separate three-dose study with 304 adolescents showed that with a third dose at 10 months after the second dose ( i.e. when cases of disease started to appear ) a strong booster response was induced . Ten months after the second dose the SBA was reduced to near pre-immunization level . Following the third dose the SBA geometric mean titer of 2.7 increased to 62.3 . One year after the third dose , the GMT was markedly higher than 6 weeks after the second dose ( 12.6 versus 8.8 ) . Thus , protection after vaccination corresponds with the level of SBA . In order to reach lasting protective levels of SBA in a population , three vaccine doses are probably required . Measurements of SBA are likely to be useful for evaluating various upcoming formulations and improvements of immunization regimens for OMV vaccines Background : New Zeal and has experienced an epidemic of Neisseria meningitidis dominated by strain B:4:P1.7b,4 since 1991 . Children younger than 5 years are at highest risk . Previous serogroup B outer membrane vesicle ( OMV ) strain specific vaccines have shown variable efficacy in this age group . Objective : To evaluate the immunogenicity , reactogenicity and safety in 16–24-month-old children of an OMV vaccine  developed against the New Zeal and epidemic strain . Methods : Children ( 332 ) aged 16–24 months were r and omized to receive the New Zeal and c and i date vaccine made using strain NZ98/254 ( B:4:P1.7b,4 ) or the Norwegian parent vaccine made using strain 44/76 ( B:15:P1.7,16 ) . Vaccines ( 25 μg/dose ) were administered at 0 , 6 and 12 weeks in this observer-blind trial . Immune response was measured by serum bactericidal assay and enzyme-linked immunosorbent assay . Sero-response was defined as a 4-fold or greater rise in serum bactericidal antibody titer compared with baseline , with titers < 1:4 required to increase to ≥1:8 to be considered a sero-response . Local and systemic reactions were monitored for 7 days after vaccination . Results : Sero-response against NZ98/254 was achieved after 3 doses in 75 % ( 95 % CI : 69–80 % ) receiving the New Zeal and c and i date vaccine by both intention to treat ( ITT ) and per protocol ( PP ) analyses . In Norwegian parent vaccinees this was seen in 3 % ( 0–12 % ) ( ITT ) and 4 % ( 0–13 % ) ( PP ) . Vaccines were well tolerated with no vaccine-related serious adverse events . Conclusion : The New Zeal and c and i date vaccine administered to these 16–24-month-old children in 3 doses was safe and elicited a promising immune response against the c and i date vaccine strain NZ98/254 ( N. meningitidis B:4:P1.7b,4 ) contributing to vaccine licensure for this age group BACKGROUND The serogroup B meningococcus is responsible for the majority of cases of meningococcal disease in temperate countries . Infants and young children < 2 years of age are at greatest risk of disease . This study assessed the immunogenicity in infants of a serogroup B meningococcal outer membrane protein vaccine  that has been used extensively in disease outbreaks in Cuba and several Latin American countries and shown to be efficacious in teenagers . METHOD One hundred five healthy infants entering the routine vaccination schedule in Havana , Cuba , were given either 2 or 3 doses of the serogroup B meningococcal vaccine VA-MENGOC-BC at 3.5 , 5.5 and 7.5 months of age . Immune response pre- and postvaccination was determined by the conventional serum bactericidal assay ( SBA ) , a more sensitive novel whole blood bactericidal assay ( WBA ) and immunoglobulin ELISA . RESULTS In 52 and 46 % of infants > 50 % killing of the vaccine serogroup B strain ( B:4:P1.19,15 ) and serogroup C strain 
    Output:
    