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 Two influenza B lineages have been co-circulating since the 1980s , and because inactivated trivalent influenza vaccine ( TIV ) contains only one B strain , it provides little/no protection against the alternate B-lineage . We assessed a c and i date inactivated quadrivalent influenza vaccine ( QIV ) containing both B lineages versus TIV in healthy adults . METHODS Subjects received one dose of QIV ( lot 1 , 2 , or 3 ) or one of two TIVs ( B strain from Victoria or Yamagata lineage ) ; r and omization was 2:2:2:1:1 . Hemagglutination-inhibition assays were performed 21-days post-vaccination ; superiority of QIV versus TIV for the alternate B-lineage was demonstrated if the 95 % confidence interval ( CI ) lower limit for the GMT ratio was ≥1.5 , and non-inferiority against the shared strains was demonstrated if the 95 % CI upper limit for the GMT ratio was ≤1.5 . Reactogenicity and safety were assessed during the post-vaccination period . NCT01196975 . RESULTS Immunogenicity of QIV lots was consistent , QIV was superior to TIV for the alternate B-lineage strain , and QIV was non-inferior versus TIVs for shared strains ( A/H1N1 , A/H3N2 , B-strain ) . Reactogenicity and safety profile of the QIV was consistent with seasonal influenza vaccines . CONCLUSION QIV provided superior immunogenicity for the added B strain without affecting the antibody response to the TIV strains , and without compromising safety Background The effectiveness of trivalent influenza vaccines may be reduced in older versus younger adults because of age-related immunosenescence . The use of an adjuvant in such a vaccine is one strategy that may combat immunosenescence , potentially by bolstering T-cell mediated responses . Methods This observer-blind study , conducted in the United States ( US ) and Spain during the 2008–2009 influenza season , evaluated the effect of Adjuvant System AS03 on specific T-cell responses to a seasonal trivalent influenza vaccine ( TIV ) in ≥65 year-old adults . Medically-stable adults aged ≥65 years were r and omly allocated to receive a single dose of AS03-adjuvanted TIV ( TIV/AS03 ) or TIV .  Healthy adults aged 18–40 years received only TIV . Blood sample s were collected on Day 0 , Day 21 , Day 42 and Day 180 . Influenza-specific CD4 + T cells , defined by the induction of the immune markers CD40L , IL-2 , IFN-γ , or TNF-α , were measured in ex vivo cultures of antigen-stimulated peripheral blood mononuclear cells . Results A total of 192 adults were vaccinated : sixty nine and seventy three ≥65 year olds received TIV/AS03 and TIV , respectively ; and fifty 18 - 40 year olds received TIV . In the ≥65 year-old group on Day 21 , the frequency of CD4 + T cells specific to the three vaccine strains was superior in the TIV/AS03 recipients to the frequency in TIV ( p < 0.001 ) . On Days 42 and 180 , the adjusted-geometric mean specific CD4 + T-cell frequencies were also higher in the TIV/AS03 recipients than in the TIV recipients ( p < 0.001 ) . Furthermore , the adjusted-geometric mean specific CD4 + T-cell frequencies were higher in the ≥65 year-old recipients of TIV/AS03 than in the18 - 40 year old recipients of TIV on Days 21 ( p = 0.006 ) and 42 ( p = 0.011 ) . Conclusion This positive effect of AS03 Adjuvant System on the CD4 + T-cell response to influenza vaccine strains in older adults could confer benefit in protection against clinical influenza disease in this population .Trial registration ( Clinical trials.gov . ) . NCT00765076 Background : Correlations between  hemagglutination-inhibition titers  ( hereafter “ titers ” ) and protection against infection have been identified in historical studies . However , limited information is available about the dynamics of how titer influences protection . Methods : Titers were measured in r and omized , placebo-controlled vaccine trials in Hong Kong among pediatrics during September 2009–December 2010 and the United States among adults during Oct 2007–April 2008 . Intermediate unobserved titers were imputed using three interpolation methods . As participants were recruited at different times leading to varying exposure to infection relative to entry , a modified proportional hazards model was developed to account for staggered entry into the studies and to quantify the correlation of titers with protection against influenza infections , adjusting for waning in titers . The model was fitted using Markov chain Monte Carlo and importance sampling . Results : A titer of 1:40 was associated with a reduced infection risk of 40%–70 % relative to a titer of 1:10 , depending on the circulating strain ; the corresponding protection associated with a titer of 1:80 was 54%–84 % . Results were robust across interpolation methods . The trivalent-inactivated vaccine reduced cumulative incidence of influenza B and influenza A(H3N2 ) infections by six percentage points ( pp ; 95 % credible interval = 2 pp , 10 pp ) and 1 pp ( 95 % credible interval = 0.3 pp , 2 pp ) respectively , but not for influenza A(H1N1)pdm09 . The live-attenuated vaccine showed little efficacy against influenza A(H3N2 ) infections . Conclusions : Titers are correlated with protection against influenza infections . The trivalent inactivated vaccine can reduce the risk of influenza A(H3N2 ) and influenza B infections in the community Background Improved influenza vaccines are needed to reduce influenza-associated complications in older adults . The aim of this study was to identify the optimal formulation of adjuvanted seasonal influenza vaccine for use in elderly people . Methods This observer-blind , r and omized study assessed the optimal formulation of adjuvanted seasonal influenza vaccine based on immunogenicity and safety in participants aged ≥65 years . Participants were r and omized ( ~200 per group ) to receive one dose of  non-adjuvanted vaccine or one of eight formulations of vaccine formulated with a squalene and tocopherol oil-in-water emulsion-based Adjuvant System ( AS03C , AS03B or AS03A , with 2.97 , 5.93 and 11.86 mg tocopherol , respectively ) together with the immunostimulant monophosphoryl lipid A ( MPL , doses of 0 , 25 or 50 mg ) . Hemagglutination-inhibition ( HI ) antibody responses and T-cell responses were assessed on Day 0 and 21 days post-vaccination . The ratio of HI-based geometric mean titers in adjuvanted versus non-adjuvanted vaccine groups were calculated and the lower limit of the 90 % confidence interval was transformed into a desirability index ( a value between 0 and 1 ) in an experimental domain for each vaccine strain , and plotted in relation to the AS03 and MPL dose combination in the formulation . This model was used to assess the optimal formulation based on HI antibody titers . Reactogenicity and safety were also assessed . The immunogenicity and safety analyses were used to evaluate the optimal formulation of adjuvanted vaccine . Results In the HI antibody-based model , an AS03 dose – response was evident ; responses against the A/H1N1 and A/H3N2 strains were higher for all adjuvanted formulations versus non-adjuvanted vaccine , and for the AS03A-MPL25 , AS03B-MPL25 and AS03B-MPL50 formulations against the B strain . Modelling using more stringent criteria ( post hoc ) showed a clear dose-range effect for the AS03 component against all strains , whereas MPL showed a limited effect . Higher T-cell responses for adjuvanted versus non-adjuvanted vaccine were observed for all except two formulations ( AS03C and AS03B-MPL25 ) . Reactogenicity increased with increasing AS03 dosage , and with MPL . No safety concerns were raised . Conclusions Five formulations containing AS03A or AS03B were identified as potential c and i date s to improve immune responses to influenza vaccination ; AS03B without MPL showed the best balance between improved immunogenicity and acceptable reactogenicity . Trial registration This trial is registered at Clinical Trials.gov , 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 We have performed a broad-ranging analysis of the adjuvant effect of a Kampo medicine , juzentaihoto ( JTT ) , on influenza vaccination in a multicenter r and omized controlled trial . In this study , the enhancing effect of JTT on antibody titer after influenza vaccination was studied for 28 weeks in elderly people who were in the high-risk group for influenza infection . In total , 91 subjects over 65 years old were recruited from four long-term-care facilities located in Chiba , Gunma , and Toyama prefectures in Japan . Participants were r and omly assigned to the JTT and the control groups .  Blood sample s were taken at 4 weeks before vaccination , at the time of vaccination , and then at 4 , 8 , 12 , and 24 weeks after vacc 
    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 Two influenza B lineages have been co-circulating since the 1980s , and because inactivated trivalent influenza vaccine ( TIV ) contains only one B strain , it provides little/no protection against the alternate B-lineage . We assessed a c and i date inactivated quadrivalent influenza vaccine ( QIV ) containing both B lineages versus TIV in healthy adults . METHODS Subjects received one dose of QIV ( lot 1 , 2 , or 3 ) or one of two TIVs ( B strain from Victoria or Yamagata lineage ) ; r and omization was 2:2:2:1:1 . Hemagglutination-inhibition assays were performed 21-days post-vaccination ; superiority of QIV versus TIV for the alternate B-lineage was demonstrated if the 95 % confidence interval ( CI ) lower limit for the GMT ratio was ≥1.5 , and non-inferiority against the shared strains was demonstrated if the 95 % CI upper limit for the GMT ratio was ≤1.5 . Reactogenicity and safety were assessed during the post-vaccination period . NCT01196975 . RESULTS Immunogenicity of QIV lots was consistent , QIV was superior to TIV for the alternate B-lineage strain , and QIV was non-inferior versus TIVs for shared strains ( A/H1N1 , A/H3N2 , B-strain ) . Reactogenicity and safety profile of the QIV was consistent with seasonal influenza vaccines . CONCLUSION QIV provided superior immunogenicity for the added B strain without affecting the antibody response to the TIV strains , and without compromising safety Background The effectiveness of trivalent influenza vaccines may be reduced in older versus younger adults because of age-related immunosenescence . The use of an adjuvant in such a vaccine is one strategy that may combat immunosenescence , potentially by bolstering T-cell mediated responses . Methods This observer-blind study , conducted in the United States ( US ) and Spain during the 2008–2009 influenza season , evaluated the effect of Adjuvant System AS03 on specific T-cell responses to a seasonal trivalent influenza vaccine ( TIV ) in ≥65 year-old adults . Medically-stable adults aged ≥65 years were r and omly allocated to receive a single dose of AS03-adjuvanted TIV ( TIV/AS03 ) or TIV .  Healthy adults aged 18–40 years received only TIV . Blood sample s were collected on Day 0 , Day 21 , Day 42 and Day 180 . Influenza-specific CD4 + T cells , defined by the induction of the immune markers CD40L , IL-2 , IFN-γ , or TNF-α , were measured in ex vivo cultures of antigen-stimulated peripheral blood mononuclear cells . Results A total of 192 adults were vaccinated : sixty nine and seventy three ≥65 year olds received TIV/AS03 and TIV , respectively ; and fifty 18 - 40 year olds received TIV . In the ≥65 year-old group on Day 21 , the frequency of CD4 + T cells specific to the three vaccine strains was superior in the TIV/AS03 recipients to the frequency in TIV ( p < 0.001 ) . On Days 42 and 180 , the adjusted-geometric mean specific CD4 + T-cell frequencies were also higher in the TIV/AS03 recipients than in the TIV recipients ( p < 0.001 ) . Furthermore , the adjusted-geometric mean specific CD4 + T-cell frequencies were higher in the ≥65 year-old recipients of TIV/AS03 than in the18 - 40 year old recipients of TIV on Days 21 ( p = 0.006 ) and 42 ( p = 0.011 ) . Conclusion This positive effect of AS03 Adjuvant System on the CD4 + T-cell response to influenza vaccine strains in older adults could confer benefit in protection against clinical influenza disease in this population .Trial registration ( Clinical trials.gov . ) . NCT00765076 Background : Correlations between  hemagglutination-inhibition titers  ( hereafter “ titers ” ) and protection against infection have been identified in historical studies . However , limited information is available about the dynamics of how titer influences protection . Methods : Titers were measured in r and omized , placebo-controlled vaccine trials in Hong Kong among pediatrics during September 2009–December 2010 and the United States among adults during Oct 2007–April 2008 . Intermediate unobserved titers were imputed using three interpolation methods . As participants were recruited at different times leading to varying exposure to infection relative to entry , a modified proportional hazards model was developed to account for staggered entry into the studies and to quantify the correlation of titers with protection against influenza infections , adjusting for waning in titers . The model was fitted using Markov chain Monte Carlo and importance sampling . Results : A titer of 1:40 was associated with a reduced infection risk of 40%–70 % relative to a titer of 1:10 , depending on the circulating strain ; the corresponding protection associated with a titer of 1:80 was 54%–84 % . Results were robust across interpolation methods . The trivalent-inactivated vaccine reduced cumulative incidence of influenza B and influenza A(H3N2 ) infections by six percentage points ( pp ; 95 % credible interval = 2 pp , 10 pp ) and 1 pp ( 95 % credible interval = 0.3 pp , 2 pp ) respectively , but not for influenza A(H1N1)pdm09 . The live-attenuated vaccine showed little efficacy against influenza A(H3N2 ) infections . Conclusions : Titers are correlated with protection against influenza infections . The trivalent inactivated vaccine can reduce the risk of influenza A(H3N2 ) and influenza B infections in the community Background Improved influenza vaccines are needed to reduce influenza-associated complications in older adults . The aim of this study was to identify the optimal formulation of adjuvanted seasonal influenza vaccine for use in elderly people . Methods This observer-blind , r and omized study assessed the optimal formulation of adjuvanted seasonal influenza vaccine based on immunogenicity and safety in participants aged ≥65 years . Participants were r and omized ( ~200 per group ) to receive one dose of  non-adjuvanted vaccine or one of eight formulations of vaccine formulated with a squalene and tocopherol oil-in-water emulsion-based Adjuvant System ( AS03C , AS03B or AS03A , with 2.97 , 5.93 and 11.86 mg tocopherol , respectively ) together with the immunostimulant monophosphoryl lipid A ( MPL , doses of 0 , 25 or 50 mg ) . Hemagglutination-inhibition ( HI ) antibody responses and T-cell responses were assessed on Day 0 and 21 days post-vaccination . The ratio of HI-based geometric mean titers in adjuvanted versus non-adjuvanted vaccine groups were calculated and the lower limit of the 90 % confidence interval was transformed into a desirability index ( a value between 0 and 1 ) in an experimental domain for each vaccine strain , and plotted in relation to the AS03 and MPL dose combination in the formulation . This model was used to assess the optimal formulation based on HI antibody titers . Reactogenicity and safety were also assessed . The immunogenicity and safety analyses were used to evaluate the optimal formulation of adjuvanted vaccine . Results In the HI antibody-based model , an AS03 dose – response was evident ; responses against the A/H1N1 and A/H3N2 strains were higher for all adjuvanted formulations versus non-adjuvanted vaccine , and for the AS03A-MPL25 , AS03B-MPL25 and AS03B-MPL50 formulations against the B strain . Modelling using more stringent criteria ( post hoc ) showed a clear dose-range effect for the AS03 component against all strains , whereas MPL showed a limited effect . Higher T-cell responses for adjuvanted versus non-adjuvanted vaccine were observed for all except two formulations ( AS03C and AS03B-MPL25 ) . Reactogenicity increased with increasing AS03 dosage , and with MPL . No safety concerns were raised . Conclusions Five formulations containing AS03A or AS03B were identified as potential c and i date s to improve immune responses to influenza vaccination ; AS03B without MPL showed the best balance between improved immunogenicity and acceptable reactogenicity . Trial registration This trial is registered at Clinical Trials.gov , 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 We have performed a broad-ranging analysis of the adjuvant effect of a Kampo medicine , juzentaihoto ( JTT ) , on influenza vaccination in a multicenter r and omized controlled trial . In this study , the enhancing effect of JTT on antibody titer after influenza vaccination was studied for 28 weeks in elderly people who were in the high-risk group for influenza infection . In total , 91 subjects over 65 years old were recruited from four long-term-care facilities located in Chiba , Gunma , and Toyama prefectures in Japan . Participants were r and omly assigned to the JTT and the control groups .  Blood sample s were taken at 4 weeks before vaccination , at the time of vaccination , and then at 4 , 8 , 12 , and 24 weeks after vacc 
    Output:
    