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: In a 3-year , r and omized , controlled , open-label phase III trial enrolling 3707 adults aged > or = 60 years we evaluated whether the immunogenicity of an intradermal trivalent inactivated seasonal influenza vaccine , containing 15 microg of haemagglutinin per strain per 0.1 ml dose , is superior to that of a conventional intramuscular vaccine . Intradermal vaccine was given using an intradermal microinjection system . After the first vaccination , both vaccines satisfied the immunogenicity criteria for influenza vaccines for older adults set out in European regulatory guidelines , and geometric mean haemagglutination inhibition antibody titers and seroprotection rates were higher ( statistically superior ) with intradermal vaccination . Higher immune responses with intradermal vaccine were also observed after the 2nd and 3rd annual vaccinations . Both vaccines were well tolerated with similar systemic reactogenicity profiles . This intradermal influenza vaccine for older adults is a beneficial option for influenza protection , consistently enhancing antibody responses without compromising safety BACKGROUD Influenza viruses cause substantial morbidity , especially in older age groups . Thus , they are amongst high priority groups for routine vaccination . However , vaccine-induced immune responses and effectiveness were reported as relatively low . This study aims to systemically compare the immune responses elicited by intramuscular ( IM ) and intradermal ( ID ) injections with inactivated seasonal influenza vaccine among the older age group . METHODS A prospect i ve , open-label , r and omized study with a total of 221 adults ( > 60 years ) were enrolled and r and omized into 2 groups . Group I ( n = 111 ) received an IM inactivated seasonal influenza vaccine while Group II ( n = 110 ) received the same vaccine ID . Demographics and co-morbidity were collected at baseline . Safety data was collected 3 days post-vaccination using diary card . HAI , NAb and NAI titers were assessed prior to vaccination and at 30 , 45 , and 60 days post-vaccination . Data was analyzed using SPSS 11.5 . RESULTS Both groups had similar BMI and co-morbidity . For ID and IM groups , significant differences were observed for seroconversion rate measured using HAI against H1N1 and H3N2 ( 58/111 vs 44/110 and 68/111 vs 54/110 , respectively ) being higher for those aged 60 - 65 years . However , no differences in HI antibody against B/Phuket were seen . For ID route , history of hyperlipidemia and hypertension were factors associated with high seroconversion rate towards influenza A ( p = .001 ) . The seroconversion rate risk ratio were 1.31 and 1.25 ( p < .05 ) against A/California/07/09(H1N1 ) and A/Songkha/308/13 ( H3N2 ) , respectively . Interestingly , the GMT ( 95 % CI ) of baseline NAI antibodies among both groups were high ( 56.57 and 54.01 in the ID and IM groups , respectively ) . A 4-fold increase measured by NAI against A/California/07/09 ( H1N1 ) were detected in 16.67 % and 20 % of participants who received ID or IM vaccination , respectively . CONCLUSIONS The seroconversion rates of HAI , NAb and NAI were modest , especially in those > 65 years of age . However , it was higher in the ID group as compared to the IM group . CLINICAL TRIAL REGISTRATION NCT02101749 We conducted a r and omized , controlled , multicenter , phase II study to evaluate the immunogenicity and safety of an investigational intradermal ( ID ) trivalent influenza vaccine ( TIV ) and a high-dose ( HD ) intramuscular ( IM ) TIV in older adults ( ≥65 years of age ) . Older adult subjects were immunized with ID vaccine containing either 15μg hemagglutinin (HA)/strain ( n=636 ) or 21μg HA/strain ( n=634 ) , with HD IM vaccine containing 60μg HA/strain ( n=320 ) , or with st and ard-dose ( SD ) IM vaccine ( Fluzone ( ® ) ; 15μg HA/strain ; n=319 ) . For comparison , younger adults ( 18 - 49 years of age ) were immunized with SD IM vaccine . In older adults  , post-vaccination geometric mean titers induced by the ID vaccines were superior to those induced by the SD IM vaccine for the A/H1N1 and A/H3N2 strains and non-inferior for the B strain . Seroconversion rates induced by the ID vaccines were superior to those induced by the SD IM vaccine in older adults for the A/H1N1 and B strains and non-inferior for the A/H3N2 strain . Results did not differ significantly for the two ID vaccine dosages . Post-vaccination geometric mean titers , seroconversion rates , and most seroprotection rates were significantly higher in HD vaccine recipients than in older adult recipients of the SD IM or ID vaccines and , for most measures , were comparable to those of younger adult SD IM vaccine recipients . Injection-site reactions , but not systemic reactions or unsolicited adverse events , were more common with the ID vaccines than with the IM vaccines . No treatment-related serious adverse events were reported . This study demonstrated that : ( 1 ) the ID and HD vaccines were well-tolerated and more immunogenic than the SD IM vaccine in older adults ; ( 2 ) the HD vaccine was more immunogenic than the ID vaccines in older adults ; and ( 3 ) the HD vaccine in older adults and the SD IM vaccine in younger adults elicited comparable antibody responses ( Clinical Trials.gov identifier no. : NCT00551031 ) Safety and immunogenicity of the influenza vaccine adjuvanted with MF59 ( FLUAD ) were compared to those of a non adjuvanted subunit vaccine in elderly subjects during three consecutive influenza seasons .  Geometric mean titres and proportions of subjects with either a > or = four-fold increase in antibody titres or with an HI titre > or = 128 after immunisation were higher in FLUAD recipients . The adjuvant effect on the magnitude of the responses was most pronounced in subjects with pre-vaccination titres < or = 40 . Although associated with more frequent mild local reactions , the adjuvanted vaccine was well tolerated . Thus , the addition of MF59 increased the immunogenicity of the subunit influenza vaccine in elderly persons with low pre-vaccination titres , who are at greatest risk of developing severe influenza disease and vaccine failure , without a clinical ly important increase in reactogenicity BACKGROUND Influenza-associated morbidity and mortality has not decreased in the last decade , despite increased receipt of vaccine . To improve the immunogenicity of influenza vaccine , a high-dose ( HD ) trivalent , inactivated influenza vaccine was developed . METHODS A multicenter , r and omized , double-blind controlled study was conducted to compare HD vaccine ( which contains 60 microg of hemagglutinin per strain ) with the licensed st and ard-dose ( SD ) vaccine ( which contains 15 microg of hemagglutinin per strain ) in adults > or = 65 years of age . RESULTS  HD vaccine was administered to 2575 subjects , and SD vaccine was administered to 1262 subjects . There was a statistically significant increase in the rates of seroconversion and mean hemagglutination inhibition titers at day 28 after vaccination among those who received HD vaccine , compared with those who received SD vaccine .  Mean postvaccination titers for individuals who received HD vaccine were 116 for H1N1 , 609 for H3N2 , and 69 for B strain ; for those who received SD vaccine , mean postvaccination titers were as 67 for H1N1 , 333 for H3N2 , and 52 for B strain . The HD vaccine met superiority criteria for both A strains , and the responses for B strain met non-inferiority criteria . Seroprotection rates were also higher for those who received HD vaccine than for those who received SD vaccine vaccine , for all strains . Local reactions were more frequent in individuals who received HD vaccine , but the reactions were mild to moderate . CONCLUSIONS There was a statistically significant increase in the level of antibody response induced by HD influenza vaccine , compared with that induced by SD vaccine , without an attendant increase in the rate or severity of clinical ly relevant adverse reactions . These results suggest that the high-dose vaccine may provide improved protective benefits for older adults . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT00391053 ABSTRACT The influenza vaccination is known as the most effective method for preventing influenza infection and its complications in the elderly .  Conventional subunit ( Agrippal S1 ; Novartis ) , MF59-adjuvanted ( Fluad ; Novartis ) , and intradermal ( IDflu15 ; Sanofi Pasteur ) influenza vaccines are widely used throughout South Korea . However , few comparative studies evaluating the safety and immunogenicity of these vaccines are available . Prior to the beginning of the 2011 - 2012 influenza season , 335 healthy elderly volunteers r and omly received one of three seasonal trivalent influenza vaccines , the conventional subunit , MF59-adjuvanted , or intradermal influenza vaccine .  Serum hemagglutination-inhibiting antibody levels were measured at the time of vaccination and at 1 and 6 months after vaccination . Adverse events were recorded prospect ively . A total of 113 conventional subunit , 111 MF59-adjuvanted , and 111 intradermal influenza vaccine volunteers were followed up during a 6-month postvaccination period . One month after vaccination , all three vaccines satisfied Committee for Medical Products for Human Use ( CHMP ) immunogenicity criteria for the A/H1N1 and A/H3N2 strains but not for the B strain . Compared with the subunit vaccine , the intradermal vaccine exhibited noninferiority , while the MF59-adjuvanted vaccine exhibited superiority . Furthermore , the MF59-adjuvanted vaccine was more immunogenic against the A/H3N2 strain than was the subunit vaccine up to 6 months postvaccination . The most common local and systemic reactions to the conventional subunit , MF59-adjuvanted , and intradermal influenza vaccines were pain at the injection site ( 7.1 % , 10.8 % , and 6.3 % , respectively ) and generalized myalgia ( 0.9 % , 8.1 % , and 5.4 % , respectively ) . Local and systemic reactions were similar among the three vaccine groups . MF59-adjuvanted vaccine exhibited superior immunogenicity compared with a conventional subunit vaccine and had a comparable safety profile . For older adults , the MF59-adjuvanted vaccine is preferable for providing superior immunogenicity It is commonly held that increased risk of influenza in the elderly is due to a decline in the Ab response to influenza vaccination . This study prospect ively evaluated the relationship between the development of influenza illness , and serum Ab titers and ex vivo cellular immune responses to influenza vaccination in community dwelling older adults including those with congestive heart failure ( CHF ) . Adults age 60 years and older ( 90 subjects ) , and 10 healthy young adult controls received the 2003 - 04 trivalent inactivated influenza vaccine .  Laboratory diagnosed influenza ( LDI ) was documented in 9 of 90 older adults .  Pre- and postvaccination Ab titers did not distinguish between subjects who would subsequently develop influenza illness ( LDI subjects ) and those who would not ( non-LDI subjects ) . In contrast , P BMC restimulated ex vivo with live influenza virus preparations showed statistically significant differences between LDI and non-LDI subjects . The mean IFN-γ : IL-10 ratio in influenza A/H3N2-stimulated P BMC was 10-fold lower in LDI vs non-LDI subjects . Pre- and postvaccination granzyme B levels were significantly lower in CHF subjects with LDI compared with subjects without LDI . In non-CHF subjects with LDI , granzyme B levels increased to high levels at the time of influenza infection . In conclusion , measures of the ex vivo cellular immune response to influenza are correlated with protection against influenza while serum Ab responses may be limited as a sole measure of vaccine efficacy in older people . Ex vivo measures of the cell-mediated immune response should be incorporated into evaluation of new vaccines for older adults Background Although seasonal influenza vaccine is effective in the elderly , immune responses to vaccination are lower in the elderly than in younger adults . Strategies to optimise responses to vaccination in the elderly include using an adjuvanted vaccine or using an intradermal vaccination route . The immunogenicity of an intradermal seasonal influenza vaccine was compared with that of an adjuvanted 
    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: In a 3-year , r and omized , controlled , open-label phase III trial enrolling 3707 adults aged > or = 60 years we evaluated whether the immunogenicity of an intradermal trivalent inactivated seasonal influenza vaccine , containing 15 microg of haemagglutinin per strain per 0.1 ml dose , is superior to that of a conventional intramuscular vaccine . Intradermal vaccine was given using an intradermal microinjection system . After the first vaccination , both vaccines satisfied the immunogenicity criteria for influenza vaccines for older adults set out in European regulatory guidelines , and geometric mean haemagglutination inhibition antibody titers and seroprotection rates were higher ( statistically superior ) with intradermal vaccination . Higher immune responses with intradermal vaccine were also observed after the 2nd and 3rd annual vaccinations . Both vaccines were well tolerated with similar systemic reactogenicity profiles . This intradermal influenza vaccine for older adults is a beneficial option for influenza protection , consistently enhancing antibody responses without compromising safety BACKGROUD Influenza viruses cause substantial morbidity , especially in older age groups . Thus , they are amongst high priority groups for routine vaccination . However , vaccine-induced immune responses and effectiveness were reported as relatively low . This study aims to systemically compare the immune responses elicited by intramuscular ( IM ) and intradermal ( ID ) injections with inactivated seasonal influenza vaccine among the older age group . METHODS A prospect i ve , open-label , r and omized study with a total of 221 adults ( > 60 years ) were enrolled and r and omized into 2 groups . Group I ( n = 111 ) received an IM inactivated seasonal influenza vaccine while Group II ( n = 110 ) received the same vaccine ID . Demographics and co-morbidity were collected at baseline . Safety data was collected 3 days post-vaccination using diary card . HAI , NAb and NAI titers were assessed prior to vaccination and at 30 , 45 , and 60 days post-vaccination . Data was analyzed using SPSS 11.5 . RESULTS Both groups had similar BMI and co-morbidity . For ID and IM groups , significant differences were observed for seroconversion rate measured using HAI against H1N1 and H3N2 ( 58/111 vs 44/110 and 68/111 vs 54/110 , respectively ) being higher for those aged 60 - 65 years . However , no differences in HI antibody against B/Phuket were seen . For ID route , history of hyperlipidemia and hypertension were factors associated with high seroconversion rate towards influenza A ( p = .001 ) . The seroconversion rate risk ratio were 1.31 and 1.25 ( p < .05 ) against A/California/07/09(H1N1 ) and A/Songkha/308/13 ( H3N2 ) , respectively . Interestingly , the GMT ( 95 % CI ) of baseline NAI antibodies among both groups were high ( 56.57 and 54.01 in the ID and IM groups , respectively ) . A 4-fold increase measured by NAI against A/California/07/09 ( H1N1 ) were detected in 16.67 % and 20 % of participants who received ID or IM vaccination , respectively . CONCLUSIONS The seroconversion rates of HAI , NAb and NAI were modest , especially in those > 65 years of age . However , it was higher in the ID group as compared to the IM group . CLINICAL TRIAL REGISTRATION NCT02101749 We conducted a r and omized , controlled , multicenter , phase II study to evaluate the immunogenicity and safety of an investigational intradermal ( ID ) trivalent influenza vaccine ( TIV ) and a high-dose ( HD ) intramuscular ( IM ) TIV in older adults ( ≥65 years of age ) . Older adult subjects were immunized with ID vaccine containing either 15μg hemagglutinin (HA)/strain ( n=636 ) or 21μg HA/strain ( n=634 ) , with HD IM vaccine containing 60μg HA/strain ( n=320 ) , or with st and ard-dose ( SD ) IM vaccine ( Fluzone ( ® ) ; 15μg HA/strain ; n=319 ) . For comparison , younger adults ( 18 - 49 years of age ) were immunized with SD IM vaccine . In older adults  , post-vaccination geometric mean titers induced by the ID vaccines were superior to those induced by the SD IM vaccine for the A/H1N1 and A/H3N2 strains and non-inferior for the B strain . Seroconversion rates induced by the ID vaccines were superior to those induced by the SD IM vaccine in older adults for the A/H1N1 and B strains and non-inferior for the A/H3N2 strain . Results did not differ significantly for the two ID vaccine dosages . Post-vaccination geometric mean titers , seroconversion rates , and most seroprotection rates were significantly higher in HD vaccine recipients than in older adult recipients of the SD IM or ID vaccines and , for most measures , were comparable to those of younger adult SD IM vaccine recipients . Injection-site reactions , but not systemic reactions or unsolicited adverse events , were more common with the ID vaccines than with the IM vaccines . No treatment-related serious adverse events were reported . This study demonstrated that : ( 1 ) the ID and HD vaccines were well-tolerated and more immunogenic than the SD IM vaccine in older adults ; ( 2 ) the HD vaccine was more immunogenic than the ID vaccines in older adults ; and ( 3 ) the HD vaccine in older adults and the SD IM vaccine in younger adults elicited comparable antibody responses ( Clinical Trials.gov identifier no. : NCT00551031 ) Safety and immunogenicity of the influenza vaccine adjuvanted with MF59 ( FLUAD ) were compared to those of a non adjuvanted subunit vaccine in elderly subjects during three consecutive influenza seasons .  Geometric mean titres and proportions of subjects with either a > or = four-fold increase in antibody titres or with an HI titre > or = 128 after immunisation were higher in FLUAD recipients . The adjuvant effect on the magnitude of the responses was most pronounced in subjects with pre-vaccination titres < or = 40 . Although associated with more frequent mild local reactions , the adjuvanted vaccine was well tolerated . Thus , the addition of MF59 increased the immunogenicity of the subunit influenza vaccine in elderly persons with low pre-vaccination titres , who are at greatest risk of developing severe influenza disease and vaccine failure , without a clinical ly important increase in reactogenicity BACKGROUND Influenza-associated morbidity and mortality has not decreased in the last decade , despite increased receipt of vaccine . To improve the immunogenicity of influenza vaccine , a high-dose ( HD ) trivalent , inactivated influenza vaccine was developed . METHODS A multicenter , r and omized , double-blind controlled study was conducted to compare HD vaccine ( which contains 60 microg of hemagglutinin per strain ) with the licensed st and ard-dose ( SD ) vaccine ( which contains 15 microg of hemagglutinin per strain ) in adults > or = 65 years of age . RESULTS  HD vaccine was administered to 2575 subjects , and SD vaccine was administered to 1262 subjects . There was a statistically significant increase in the rates of seroconversion and mean hemagglutination inhibition titers at day 28 after vaccination among those who received HD vaccine , compared with those who received SD vaccine .  Mean postvaccination titers for individuals who received HD vaccine were 116 for H1N1 , 609 for H3N2 , and 69 for B strain ; for those who received SD vaccine , mean postvaccination titers were as 67 for H1N1 , 333 for H3N2 , and 52 for B strain . The HD vaccine met superiority criteria for both A strains , and the responses for B strain met non-inferiority criteria . Seroprotection rates were also higher for those who received HD vaccine than for those who received SD vaccine vaccine , for all strains . Local reactions were more frequent in individuals who received HD vaccine , but the reactions were mild to moderate . CONCLUSIONS There was a statistically significant increase in the level of antibody response induced by HD influenza vaccine , compared with that induced by SD vaccine , without an attendant increase in the rate or severity of clinical ly relevant adverse reactions . These results suggest that the high-dose vaccine may provide improved protective benefits for older adults . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT00391053 ABSTRACT The influenza vaccination is known as the most effective method for preventing influenza infection and its complications in the elderly .  Conventional subunit ( Agrippal S1 ; Novartis ) , MF59-adjuvanted ( Fluad ; Novartis ) , and intradermal ( IDflu15 ; Sanofi Pasteur ) influenza vaccines are widely used throughout South Korea . However , few comparative studies evaluating the safety and immunogenicity of these vaccines are available . Prior to the beginning of the 2011 - 2012 influenza season , 335 healthy elderly volunteers r and omly received one of three seasonal trivalent influenza vaccines , the conventional subunit , MF59-adjuvanted , or intradermal influenza vaccine .  Serum hemagglutination-inhibiting antibody levels were measured at the time of vaccination and at 1 and 6 months after vaccination . Adverse events were recorded prospect ively . A total of 113 conventional subunit , 111 MF59-adjuvanted , and 111 intradermal influenza vaccine volunteers were followed up during a 6-month postvaccination period . One month after vaccination , all three vaccines satisfied Committee for Medical Products for Human Use ( CHMP ) immunogenicity criteria for the A/H1N1 and A/H3N2 strains but not for the B strain . Compared with the subunit vaccine , the intradermal vaccine exhibited noninferiority , while the MF59-adjuvanted vaccine exhibited superiority . Furthermore , the MF59-adjuvanted vaccine was more immunogenic against the A/H3N2 strain than was the subunit vaccine up to 6 months postvaccination . The most common local and systemic reactions to the conventional subunit , MF59-adjuvanted , and intradermal influenza vaccines were pain at the injection site ( 7.1 % , 10.8 % , and 6.3 % , respectively ) and generalized myalgia ( 0.9 % , 8.1 % , and 5.4 % , respectively ) . Local and systemic reactions were similar among the three vaccine groups . MF59-adjuvanted vaccine exhibited superior immunogenicity compared with a conventional subunit vaccine and had a comparable safety profile . For older adults , the MF59-adjuvanted vaccine is preferable for providing superior immunogenicity It is commonly held that increased risk of influenza in the elderly is due to a decline in the Ab response to influenza vaccination . This study prospect ively evaluated the relationship between the development of influenza illness , and serum Ab titers and ex vivo cellular immune responses to influenza vaccination in community dwelling older adults including those with congestive heart failure ( CHF ) . Adults age 60 years and older ( 90 subjects ) , and 10 healthy young adult controls received the 2003 - 04 trivalent inactivated influenza vaccine .  Laboratory diagnosed influenza ( LDI ) was documented in 9 of 90 older adults .  Pre- and postvaccination Ab titers did not distinguish between subjects who would subsequently develop influenza illness ( LDI subjects ) and those who would not ( non-LDI subjects ) . In contrast , P BMC restimulated ex vivo with live influenza virus preparations showed statistically significant differences between LDI and non-LDI subjects . The mean IFN-γ : IL-10 ratio in influenza A/H3N2-stimulated P BMC was 10-fold lower in LDI vs non-LDI subjects . Pre- and postvaccination granzyme B levels were significantly lower in CHF subjects with LDI compared with subjects without LDI . In non-CHF subjects with LDI , granzyme B levels increased to high levels at the time of influenza infection . In conclusion , measures of the ex vivo cellular immune response to influenza are correlated with protection against influenza while serum Ab responses may be limited as a sole measure of vaccine efficacy in older people . Ex vivo measures of the cell-mediated immune response should be incorporated into evaluation of new vaccines for older adults Background Although seasonal influenza vaccine is effective in the elderly , immune responses to vaccination are lower in the elderly than in younger adults . Strategies to optimise responses to vaccination in the elderly include using an adjuvanted vaccine or using an intradermal vaccination route . The immunogenicity of an intradermal seasonal influenza vaccine was compared with that of an adjuvanted 
    Output:
    