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: Background : Children have high morbidity and hospitalization rates from seasonal influenza . Meta-analyses suggest that conventional inactivated influenza vaccines are of low efficacy in young children , making vaccines that induce greater and broader immune protection in this vulnerable population a medical priority . Adjuvanted influenza vaccines may offer a solution . Subjects and Methods : Unprimed healthy children ( 6 to < 36 months ) were enrolled in an observer-blinded study and r and omly assigned to receive 2 doses of MF59-adjuvanted vaccine ( Sub/MF59 , n = 130 ) or nonadjuvanted split vaccine ( split , n = 139 ) ; subgroups of these ( n = 43 and 46 , respectively ) received a booster dose 1 year later . Safety and clinical tolerability were assessed after each dose . Hemagglutination inhibition antibody titers were measured against influenza A and B strains included in the formulation of the vaccines and against mismatched strains . Results : Clinical tolerability and safety were generally comparable between vaccine groups , though some transient , mild solicited reactions were more frequent in the Sub/MF59 group . Postvaccination hemagglutination inhibition antibody titers to all 3 vaccine strains were significantly higher with Sub/MF59 than with split vaccine ( all comparisons P < 0.001 ) after each of the 3 vaccine doses . In addition , Sub/MF59 induced significantly higher cross-reactivity against A/H3N2 and A/H1N1 mismatched strains . Conclusion : MF59-adjuvanted influenza vaccine was well tolerated in healthy young children after each of 3 doses and induced greater , longer-lasting , and broader immune responses than a nonadjuvanted split vaccine . The enhanced immunogenicity of the adjuvanted vaccine was most evident in very young children and for the B vaccine strain Introduction The substantial p and emic ( A/H1N1v ) influenza disease burden in children highlights the need for effective vaccination . We report the results of modern cell culture technology , lower doses of antigen , and different doses of MF59 ® adjuvant ( Novartis Vaccines , Marburg , Germany ) , on the immunogenicity and safety profile in a healthy Japanese pediatric population . Methods A total of 123 children from 6 months to 19 years of age were r and omly assigned in a 1:1 ratio to receive , at 21-day intervals , two doses of either 3.75 μg antigen with 50 % of the st and ard MF59 dose ( group A ) or 7.5 μg antigen and 100 % st and ard MF59 dose ( group  B ) . Antibody levels were measured by hemagglutinin inhibition ( HI ) and microneutralization assays on day 1 and on days 22 and 43 ( 3 weeks after the first and second vaccinations , respectively ) . Solicited adverse events were reported for 7 days after each injection and spontaneous events were reported throughout the study period . Results At 3 weeks after the first vaccination , seroprotective HI antibodies ( titers ≥40 ) were observed in 56 % and 78 % of subjects from groups A and B , respectively ; 100 % in both groups exhibited HI titers ≥40 after the second dose . The reactogenicity profile was acceptable , with local and systemic reactions described as mainly mild to moderate in severity . Five serious adverse events were reported , but none related to the study vaccine . Conclusion One dose of cell culture-derived A/H1N1v vaccine containing 7.5 μ g antigen with the full MF59 adjuvant dose was immunogenic and well tolerated in healthy Japanese children , meeting all three European Union Committee for Medicinal Products for Human Use ( EU CHMP ) licensure criteria . Two doses of 3.75 μg antigen with 50 % of the st and ard MF59 dose fulfilled these licensure criteria BACKGROUND There is an urgent need for a vaccine that is effective against the 2009 p and emic influenza A ( H1N1 ) virus . METHODS A split-virus , inactivated c and i date vaccine against the 2009 H1N1 virus was manufactured , and we evaluated its safety and immunogenicity in a r and omized clinical trial . Subjects were between 3 and 77 years of age , stratified into four age groups . The immunization schedule consisted of two vaccinations , 21 days apart . Subjects were injected with placebo or with vaccine , with or without alum adjuvant , at doses of 7.5 microg , 15 microg , or 30 microg . Serologic analysis was performed at baseline and on days 21 and 35 . RESULTS A total of 2200 subjects received one dose , and 2103 ( 95.6 % ) received the second dose , of vaccine or placebo .  No severe adverse side effects associated with the vaccine were noted . In the nonadjuvanted-vaccine groups , injection-site or systemic reactions , most mild in nature , were noted in 5.5 to 15.9 % of subjects . Among the subjects receiving 15 microg of nonadjuvanted vaccine , a hemagglutination-inhibition titer of 1:40 or more was achieved by day 21 in 74.5 % of subjects between 3 and 11 years of age , 97.1 % of subjects between 12 and 17 years , 97.1 % of subjects between 18 and 60 years , and 79.1 % of subjects 61 years of age or older ; by day 35 , the titer had been achieved in 98.1 % , 100 % , 97.1 % , and 93.3 % of subjects , respectively . The proportion with a titer of 1:40 or more was generally highest among the subjects receiving 30 microg of vaccine , with or without adjuvant . Vaccine without adjuvant was associated with fewer local reactions and greater immune responses than was vaccine with adjuvant . CONCLUSIONS These data suggest that a single dose of 15 microg of hemagglutinin antigen without alum adjuvant induces a typically protective immune response in the majority of subjects between 12 and 60 years of age . Lesser immune responses were seen after a single dose of vaccine in younger and older subjects . ( Clinical Trials.gov number , NCT00975572 ) INTRODUCTION Effective vaccination strategies are required to combat future influenza p and emics . Here we report the results of three independent clinical trials performed in Japan to assess the immunogenicity , tolerability and safety of varying doses of a cell culture-derived MF59( ® )-adjuvanted A/H1N1 p and emic vaccine in healthy Japanese paediatric , adult and elderly subjects . METHODS One hundred and twenty-three children ( 6 months-18 years ) , and 200 adults ( 19 - 60 years ) were r and omly assigned in a 1:1 ratio to receive two doses of vaccine containing either 7.5 μg antigen with a full ( 9.75 mg ) adjuvant dose , or 3.75 μg antigen with a half ( 4.875 mg ) adjuvant dose . One hundred elderly ( ≥ 61 years ) subjects received only the low antigen/adjuvant vaccine formulation . Immunogenicity was assessed by haemagglutination inhibition assay at baseline and three weeks after the first and second vaccine doses on Days 22 and 43 , respectively . Solicited and unsolicited adverse reactions were recorded for seven and 21 days post-immunization , respectively . RESULTS In adult and elderly subjects , a single low antigen/adjuvant dose vaccination was sufficient to meet all of the three European licensure criteria established for influenza vaccines . One high , or two low antigen/adjuvant dose vaccinations were required to meet the licensure criteria in paediatric subjects . Both vaccine formulations were well tolerated , with the majority of adverse reactions mild to moderate in severity . None of the five serious adverse events reported throughout the three trials were considered to be vaccine-related by the investigators . CONCLUSION The use of MF59 adjuvant allows for much reduced vaccine antigen content , and a single dose administration schedule in adults and the elderly . The production of p and emic vaccine using modern cell culture techniques is highly advantageous in terms of the quantity , quality , and rapidity of antigen production ; these benefits , in combination with the use of MF59 , maximize manufacturing capacity and global vaccine supply . These data support the suitability of the investigational vaccine for use in the Japanese paediatric , adult , and elderly population INTRODUCTION An observational , non-comparative , prospect i ve , surveillance study of individuals vaccinated with the MF59-adjuvanted A/H1N1 influenza vaccine , Focetria , ( Novartis Vaccines & Diagnostics , Siena , Italy ) , was performed in Italy during the 2009 A/H1N1 influenza p and emic . METHOD This study assessed the short-term ( six-week ) safety profile of the investigational vaccine in real time . After vaccination ( N=7943 ) , adverse events ( AE ) were assessed using both active ( telephone ) and passive ( healthcare data base ) follow-up in enrolled vaccinated subjects , including infants ( 6 - 23 months ) , pregnant women , and the immunosuppressed . The treating physicians of all subjects experiencing AEs post-vaccination were consulted for clinical information on the conditions reported . All AEs were coded according to ICD-10 . RESULTS A total of 1583 AEs occurred during the study , 67 ( 4.2 % ) of which were serious adverse events ( SAEs ) . One SAE was considered to be possibly related to vaccination ( transitory and ill-defined neurologic disorder experienced by a 16-year-old asthmatic male ) . Three adverse events of special interest ( AESI ) were identified ( convulsions experienced by two epileptic subjects ) , none of which were considered to be vaccine-related . Six individuals died during the study period , in each case the cause of death was not related to vaccination ( four cases of severe underlying co-morbidity , one case of psychoactive drug misuse , and one case of acute myocardial infa rct ion ) . CONCLUSIONS No cases of clinical ly relevant AEs , SAEs , or AESI were observed within a six-week period of vaccine administration . In accordance with existing clinical and post-marketing safety data , the results of this active surveillance study demonstrate a good safety profile for the MF59-adjuvanted A/H1N1 vaccine , Focetria , within the general population Background : The successful vaccination of children 6 to 36 months of age against 2009 A/H1N1 influenza was essential to help reduce the burden of p and emic disease in both the pediatric and adult population s. Objectives : We compared the immunogenicity and safety of 4 alternative monovalent vaccine formulations to identify which provided optimal levels of seroprotection according to the US and European Union ( EU ) licensure criteria . Subjects and Methods : A total of 654 healthy subjects ( 6 to < 36 months old ) were given 2 vaccine doses 3 weeks apart . Participants were assigned to 1 of the 4 immunization groups , receiving MF59-adjuvanted ( Novartis Vaccines , Marburg , Germany ) vaccine either containing 3.75 & mgr;g or 7.5 & mgr;g of A/H1N1 California/7/2009 antigen , or nonadjuvanted vaccine containing 7.5 & mgr;g or 15 & mgr;g of antigen .  Antibody titers were assessed by hemagglutination inhibition assay 3 weeks , 3 months and 1 year after immunization . Vaccine safety was monitored throughout the study . Results : After 1 dose , both adjuvanted formulations met the US and EU criteria for seroconversion ; the 15 & mgr;g nonadjuvanted vaccine met the EU criterion for seroconversion alone . The US and EU criteria for seroprotection were only met by adjuvanted groups . MF59-adjuvanted formulations alone result ed in clinical ly significant persisting antibody titers after 12 months . All vaccines were well tolerated . Conclusions : A single dose of MF59-adjuvanted vaccine containing 3.75 & mgr;g A/H1N1 antigen was highly immunogenic , met both the US and EU licensure criteria and was well tolerated . These data support the suitability of this monovalent vaccine formulation for p and emic use in children 6 to < 36 months of age BACKGROUND The current influenza p and emic calls for a safe and effective vaccine . We assessed the safety and immunogenicity of eight formulations of 2009 p and emic influenza A H1N1 vaccine produced by ten Chinese manufacturers . METHODS In this multicentre , double-blind , r and omised trial , 12 691 people aged 3 years or older were recruited in ten centres in China . In each centre , participants were stratified by age and r and omly assigned by a r and om number table to receive one of several vaccine formulations or placebo . The study assessed eight formulations : split-virion formulation containing 7.5 microg , 15 microg , or 30 microg haemagglutinin per dose , with or without al 
    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: Background : Children have high morbidity and hospitalization rates from seasonal influenza . Meta-analyses suggest that conventional inactivated influenza vaccines are of low efficacy in young children , making vaccines that induce greater and broader immune protection in this vulnerable population a medical priority . Adjuvanted influenza vaccines may offer a solution . Subjects and Methods : Unprimed healthy children ( 6 to < 36 months ) were enrolled in an observer-blinded study and r and omly assigned to receive 2 doses of MF59-adjuvanted vaccine ( Sub/MF59 , n = 130 ) or nonadjuvanted split vaccine ( split , n = 139 ) ; subgroups of these ( n = 43 and 46 , respectively ) received a booster dose 1 year later . Safety and clinical tolerability were assessed after each dose . Hemagglutination inhibition antibody titers were measured against influenza A and B strains included in the formulation of the vaccines and against mismatched strains . Results : Clinical tolerability and safety were generally comparable between vaccine groups , though some transient , mild solicited reactions were more frequent in the Sub/MF59 group . Postvaccination hemagglutination inhibition antibody titers to all 3 vaccine strains were significantly higher with Sub/MF59 than with split vaccine ( all comparisons P < 0.001 ) after each of the 3 vaccine doses . In addition , Sub/MF59 induced significantly higher cross-reactivity against A/H3N2 and A/H1N1 mismatched strains . Conclusion : MF59-adjuvanted influenza vaccine was well tolerated in healthy young children after each of 3 doses and induced greater , longer-lasting , and broader immune responses than a nonadjuvanted split vaccine . The enhanced immunogenicity of the adjuvanted vaccine was most evident in very young children and for the B vaccine strain Introduction The substantial p and emic ( A/H1N1v ) influenza disease burden in children highlights the need for effective vaccination . We report the results of modern cell culture technology , lower doses of antigen , and different doses of MF59 ® adjuvant ( Novartis Vaccines , Marburg , Germany ) , on the immunogenicity and safety profile in a healthy Japanese pediatric population . Methods A total of 123 children from 6 months to 19 years of age were r and omly assigned in a 1:1 ratio to receive , at 21-day intervals , two doses of either 3.75 μg antigen with 50 % of the st and ard MF59 dose ( group A ) or 7.5 μg antigen and 100 % st and ard MF59 dose ( group  B ) . Antibody levels were measured by hemagglutinin inhibition ( HI ) and microneutralization assays on day 1 and on days 22 and 43 ( 3 weeks after the first and second vaccinations , respectively ) . Solicited adverse events were reported for 7 days after each injection and spontaneous events were reported throughout the study period . Results At 3 weeks after the first vaccination , seroprotective HI antibodies ( titers ≥40 ) were observed in 56 % and 78 % of subjects from groups A and B , respectively ; 100 % in both groups exhibited HI titers ≥40 after the second dose . The reactogenicity profile was acceptable , with local and systemic reactions described as mainly mild to moderate in severity . Five serious adverse events were reported , but none related to the study vaccine . Conclusion One dose of cell culture-derived A/H1N1v vaccine containing 7.5 μ g antigen with the full MF59 adjuvant dose was immunogenic and well tolerated in healthy Japanese children , meeting all three European Union Committee for Medicinal Products for Human Use ( EU CHMP ) licensure criteria . Two doses of 3.75 μg antigen with 50 % of the st and ard MF59 dose fulfilled these licensure criteria BACKGROUND There is an urgent need for a vaccine that is effective against the 2009 p and emic influenza A ( H1N1 ) virus . METHODS A split-virus , inactivated c and i date vaccine against the 2009 H1N1 virus was manufactured , and we evaluated its safety and immunogenicity in a r and omized clinical trial . Subjects were between 3 and 77 years of age , stratified into four age groups . The immunization schedule consisted of two vaccinations , 21 days apart . Subjects were injected with placebo or with vaccine , with or without alum adjuvant , at doses of 7.5 microg , 15 microg , or 30 microg . Serologic analysis was performed at baseline and on days 21 and 35 . RESULTS A total of 2200 subjects received one dose , and 2103 ( 95.6 % ) received the second dose , of vaccine or placebo .  No severe adverse side effects associated with the vaccine were noted . In the nonadjuvanted-vaccine groups , injection-site or systemic reactions , most mild in nature , were noted in 5.5 to 15.9 % of subjects . Among the subjects receiving 15 microg of nonadjuvanted vaccine , a hemagglutination-inhibition titer of 1:40 or more was achieved by day 21 in 74.5 % of subjects between 3 and 11 years of age , 97.1 % of subjects between 12 and 17 years , 97.1 % of subjects between 18 and 60 years , and 79.1 % of subjects 61 years of age or older ; by day 35 , the titer had been achieved in 98.1 % , 100 % , 97.1 % , and 93.3 % of subjects , respectively . The proportion with a titer of 1:40 or more was generally highest among the subjects receiving 30 microg of vaccine , with or without adjuvant . Vaccine without adjuvant was associated with fewer local reactions and greater immune responses than was vaccine with adjuvant . CONCLUSIONS These data suggest that a single dose of 15 microg of hemagglutinin antigen without alum adjuvant induces a typically protective immune response in the majority of subjects between 12 and 60 years of age . Lesser immune responses were seen after a single dose of vaccine in younger and older subjects . ( Clinical Trials.gov number , NCT00975572 ) INTRODUCTION Effective vaccination strategies are required to combat future influenza p and emics . Here we report the results of three independent clinical trials performed in Japan to assess the immunogenicity , tolerability and safety of varying doses of a cell culture-derived MF59( ® )-adjuvanted A/H1N1 p and emic vaccine in healthy Japanese paediatric , adult and elderly subjects . METHODS One hundred and twenty-three children ( 6 months-18 years ) , and 200 adults ( 19 - 60 years ) were r and omly assigned in a 1:1 ratio to receive two doses of vaccine containing either 7.5 μg antigen with a full ( 9.75 mg ) adjuvant dose , or 3.75 μg antigen with a half ( 4.875 mg ) adjuvant dose . One hundred elderly ( ≥ 61 years ) subjects received only the low antigen/adjuvant vaccine formulation . Immunogenicity was assessed by haemagglutination inhibition assay at baseline and three weeks after the first and second vaccine doses on Days 22 and 43 , respectively . Solicited and unsolicited adverse reactions were recorded for seven and 21 days post-immunization , respectively . RESULTS In adult and elderly subjects , a single low antigen/adjuvant dose vaccination was sufficient to meet all of the three European licensure criteria established for influenza vaccines . One high , or two low antigen/adjuvant dose vaccinations were required to meet the licensure criteria in paediatric subjects . Both vaccine formulations were well tolerated , with the majority of adverse reactions mild to moderate in severity . None of the five serious adverse events reported throughout the three trials were considered to be vaccine-related by the investigators . CONCLUSION The use of MF59 adjuvant allows for much reduced vaccine antigen content , and a single dose administration schedule in adults and the elderly . The production of p and emic vaccine using modern cell culture techniques is highly advantageous in terms of the quantity , quality , and rapidity of antigen production ; these benefits , in combination with the use of MF59 , maximize manufacturing capacity and global vaccine supply . These data support the suitability of the investigational vaccine for use in the Japanese paediatric , adult , and elderly population INTRODUCTION An observational , non-comparative , prospect i ve , surveillance study of individuals vaccinated with the MF59-adjuvanted A/H1N1 influenza vaccine , Focetria , ( Novartis Vaccines & Diagnostics , Siena , Italy ) , was performed in Italy during the 2009 A/H1N1 influenza p and emic . METHOD This study assessed the short-term ( six-week ) safety profile of the investigational vaccine in real time . After vaccination ( N=7943 ) , adverse events ( AE ) were assessed using both active ( telephone ) and passive ( healthcare data base ) follow-up in enrolled vaccinated subjects , including infants ( 6 - 23 months ) , pregnant women , and the immunosuppressed . The treating physicians of all subjects experiencing AEs post-vaccination were consulted for clinical information on the conditions reported . All AEs were coded according to ICD-10 . RESULTS A total of 1583 AEs occurred during the study , 67 ( 4.2 % ) of which were serious adverse events ( SAEs ) . One SAE was considered to be possibly related to vaccination ( transitory and ill-defined neurologic disorder experienced by a 16-year-old asthmatic male ) . Three adverse events of special interest ( AESI ) were identified ( convulsions experienced by two epileptic subjects ) , none of which were considered to be vaccine-related . Six individuals died during the study period , in each case the cause of death was not related to vaccination ( four cases of severe underlying co-morbidity , one case of psychoactive drug misuse , and one case of acute myocardial infa rct ion ) . CONCLUSIONS No cases of clinical ly relevant AEs , SAEs , or AESI were observed within a six-week period of vaccine administration . In accordance with existing clinical and post-marketing safety data , the results of this active surveillance study demonstrate a good safety profile for the MF59-adjuvanted A/H1N1 vaccine , Focetria , within the general population Background : The successful vaccination of children 6 to 36 months of age against 2009 A/H1N1 influenza was essential to help reduce the burden of p and emic disease in both the pediatric and adult population s. Objectives : We compared the immunogenicity and safety of 4 alternative monovalent vaccine formulations to identify which provided optimal levels of seroprotection according to the US and European Union ( EU ) licensure criteria . Subjects and Methods : A total of 654 healthy subjects ( 6 to < 36 months old ) were given 2 vaccine doses 3 weeks apart . Participants were assigned to 1 of the 4 immunization groups , receiving MF59-adjuvanted ( Novartis Vaccines , Marburg , Germany ) vaccine either containing 3.75 & mgr;g or 7.5 & mgr;g of A/H1N1 California/7/2009 antigen , or nonadjuvanted vaccine containing 7.5 & mgr;g or 15 & mgr;g of antigen .  Antibody titers were assessed by hemagglutination inhibition assay 3 weeks , 3 months and 1 year after immunization . Vaccine safety was monitored throughout the study . Results : After 1 dose , both adjuvanted formulations met the US and EU criteria for seroconversion ; the 15 & mgr;g nonadjuvanted vaccine met the EU criterion for seroconversion alone . The US and EU criteria for seroprotection were only met by adjuvanted groups . MF59-adjuvanted formulations alone result ed in clinical ly significant persisting antibody titers after 12 months . All vaccines were well tolerated . Conclusions : A single dose of MF59-adjuvanted vaccine containing 3.75 & mgr;g A/H1N1 antigen was highly immunogenic , met both the US and EU licensure criteria and was well tolerated . These data support the suitability of this monovalent vaccine formulation for p and emic use in children 6 to < 36 months of age BACKGROUND The current influenza p and emic calls for a safe and effective vaccine . We assessed the safety and immunogenicity of eight formulations of 2009 p and emic influenza A H1N1 vaccine produced by ten Chinese manufacturers . METHODS In this multicentre , double-blind , r and omised trial , 12 691 people aged 3 years or older were recruited in ten centres in China . In each centre , participants were stratified by age and r and omly assigned by a r and om number table to receive one of several vaccine formulations or placebo . The study assessed eight formulations : split-virion formulation containing 7.5 microg , 15 microg , or 30 microg haemagglutinin per dose , with or without al 
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