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 / Objectives : Vitamin D mediates immunomodulatory functions , and its deficiency has been associated with an increased prevalence of immunological diseases . The supplementation of vitamin D might be therapeutically beneficial , for example , in lupus erythematosus patients . However , its affect on established recall immune responses is undefined . Subjects/ Methods : In all , 32 individuals were r and omized in a placebo controlled , double-blind setting , and received vitamin D ( daily 2000 IU ) for 10 weeks followed by tetanus toxoid ( TT ) booster immunization . Results : During vitamin D supplementation the median 25-hydroxyvitamin D serum concentration increased to 80.3 nM , which as expected decreased in the placebo group to 29.1 nM during the ultraviolet-deprived winter months . The TT-specific immunoglobulin G ( IgG ) boost efficiency was marginal higher in the vitamin D group ( P=0.04 ) . The increase of the 25-hydroxyvitamin D levels correlated with the increase of TT – IgG serum concentrations . The induction of specific serum IgA and specific antibody secreting cells was comparable between both groups . Accordingly , the TT-specific and polyclonally triggered T-cell cytokine profiles were stable as well . Conclusions : Vitamin D supplementation was successful and booster immunization induced efficiently specific antibodies titers Abstract Objective To study the effect of vaccination on  mortality before 2 years of age in a developing country . Design Prospect i ve cohort study . Setting Rural communities in Burkina Faso . Participants 9085 children born in the study area between 1985 and 1993 . Main outcome measure Child death rate . Results Mortality before 2 years of age was lower in children who had been vaccinated : those vaccinated with BCG only had significantly lower mortality ( risk ratio for vaccinated v unvaccinated children 0.37 , 95 % confidence interval 0.29 to 0.48 ) as did those vaccinated with diphtheria , tetanus , and pertussis only ( 0.24 , 0.13 to 0.43 ) . The second dose of diphtheria , tetanus , and pertussis was not associated with lower mortality ( 0.80 , 0.58 to 1.12 ) . Conclusion Vaccination with diphtheria , tetanus , and pertussis as well as BCG is associated with better survival of children up to 2 years of age OBJECTIVES To evaluate the safety and immunogenicity of an additional birth dose of diphtheria , tetanus , and acellular pertussis vaccine ( DTaP ) . STUDY DESIGN Fifty infants between 2 to 14 days of age were r and omly assigned to receive either DTaP and hepatitis B vaccines ( experimental ) or hepatitis B alone ( control ) at birth . At 2 , 4 , 6 , and 17 months of age , DTaP and routine vaccines were administered to both groups . Safety data were collected after each dose , and sera were obtained at birth , 6 , 7 , 17 , and 18 months . Immune responses to pertussis toxin , filamentous hemagglutinin , pertactin , and fimbriae were measured by enzyme-linked immunosorbent assay ; responses to other vaccines were assessed . RESULTS No differences were seen between the 2 groups in either local or systemic reactions ; all vaccines were well tolerated . Compared with the control group , infants in the experimental group demonstrated significantly lower geometric mean antibody concentrations for pertussis toxin and pertactin 6 , 7 , and 18 months , for fimbrae at 6 , 7 , 17 , and 18 months , and for FHA at 18 months , and lower geometric mean antibody concentrations for diphtheria at 7 months . Immune responses to all other vaccine antigens were comparable . CONCLUSION Administration of an additional dose of DTaP at birth was safe but was associated with a significantly lower response to diphtheria and 3 of 4 pertussis antigens compared with controls Background / Objectives : Vitamin E is an essential fat-soluble vitamin that has been shown to induce favorable effects on animal and human immune systems . The objective of this study was to assess the effects of tocotrienol-rich fraction ( TRF ) supplementation on immune response following tetanus toxoid ( TT ) vaccine challenge in healthy female volunteers . Subjects/ Methods : In this double-blinded , placebo-controlled clinical trial , participants were r and omly assigned to receive either placebo ( control group ) or 400 mg of TRF ( study group ) supplementation daily . Over the 2-month period of the study , volunteers were asked to attend three clinical sessions ( that is , on days 0 , 28 and 56 ) and blood sample s were obtained from the volunteers during the follow-up . On day 28 , all volunteers were also vaccinated with the TT vaccine ( 20 Lf ) intramuscularly . Results : The results from the clinical trial showed that TRF supplementation significantly increased the total vitamin E level in the plasma of the TRF-supplemented volunteers compared with the placebo group , indicating overall compliance . Volunteers supplemented with TRF showed a significantly ( P<0.05 ) enhanced production of interferon-γ and interleukin (IL)-4 by the mitogen or TT-stimulated leukocytes compared with the control group . Volunteers from the TRF group produced significantly ( P<0.05 ) lower amounts of IL-6 compared with the placebo group . Anti-TT IgG production was also significantly ( P<0.05 ) augmented in the TRF-supplemented group compared with the placebo group . Conclusions : We conclude that TRF has immunostimulatory effects and potential clinical benefits to enhance immune response to vaccines BACKGROUND In most tuberculosis ( TB ) endemic countries , bacillus Calmette-Guérin ( BCG ) is usually given around birth to prevent severe TB in infants . The neonatal immune system is immature . Our hypothesis was that delaying BCG vaccination from birth to 10 weeks of age would enhance the vaccine-induced immune response . METHODS In a r and omized clinical trial , BCG was administered intradermally either at birth ( n=25 ) or at 10 weeks of age ( n=21 ) . Ten weeks after vaccination , and at 1 year of age , vaccine-specific CD4 and CD8 T cell responses were measured with a whole blood intracellular cytokine assay . RESULTS Infants who received delayed BCG vaccination demonstrated higher frequencies of BCG-specific CD4 T cells , particularly polyfunctional T cells co-expressing IFN-gamma , TNF-alpha and IL-2 , and most strikingly at 1 year of age . CONCLUSIONS Delaying BCG vaccination from birth to 10 weeks of age enhances the quantitative and qualitative BCG-specific T cell response , when measured at 1 year of age BACKGROUND Bacille Calmette-Guérin ( BCG ) is a strong T helper 1 incentive and , thus , may contribute to a decreased risk of T helper 2-dependent atopic disease . OBJECTIVE To investigate the natural course of specific immunoglobulin E ( IgE ) responses and atopic disease in  BCG-vaccinated and nonvaccinated children . PARTICIPANTS Seven hundred seventy-four children from a prospect ively followed birth cohort . OUTCOME MEASURES Physical examination and case history were performed at 3 , 6 , 12 , 18 , 24 , 36 , 48 , 60 , 72 , and 84 months of age . Total and specific serum IgE levels to 9 common inhalant and food allergens were determined ( CAP ; Pharmacia , Freiburg , Germany ) at 12 , 24 , 36 , 60 , 72 , and 84 months of age . Purified protein derivative ( PPD ) skin testing was performed at 84 months . RESULTS Period and lifetime prevalences of atopic dermatitis and recurrent wheezing tended to be lower in the BCG-vaccinated group early in life , whereas no such trend was found after the second birthday or for allergic rhinitis . The proportion of children remaining free of clinical manifestations tended to be higher in the BCG-vaccinated group but differences decreased over time . No statistically significant differences were found for total IgE levels ( median ) . Atopic sensitization tended to be lower among BCG-vaccinated children during the first 2 years of life . The diameter of the skin reaction to PPD did not correlate with total serum IgE. Clinical and serologic correlates of atopy were not significantly different between children with a skin test diameter of > /=5 mm and those with a smaller diameter . CONCLUSION These results do not support the hypothesis that BCG vaccination in early infancy is associated with a subsequently markedly decreased risk of atopic sensitization or allergy . In addition , PPD skin test reactivity was not impaired in atopic individuals Bacillus Camette-Guérin ( BCG ) vaccine is the only licensed vaccine against tuberculosis , yet its protective efficacy is highly variable between different geographical regions . We hypothesized that exposure to nontuberculous mycobacteria attenuates BCG immunogenicity by inducing mycobacterial-specific regulatory T cells ( Tregs ) . Gambian neonates were recruited at birth and r and omized to receive  BCG vaccination  either at birth or at 4 1/2 mo . Mycobacterial immune responses were assessed at birth , 4 1/2 , and 9 mo of age . At 4 1/2 mo of age the BCG naive individuals had detectable mycobacterial responses , including increased IL-10 production suggesting environmental priming . Vaccination at birth significantly enhanced Th1 , Th2 , IL-6 , IL-17 , and Treg responses in mycobacterial cultures at 4 1/2 mo compared with the BCG naive group . Analyzing results at 4 1/2 mo postvaccination revealed lower IFN-γ , IL-6 , and IL-17 responses in the delayed BCG vaccine group compared with those vaccinated at birth , but this did not relate to Treg levels prevaccination . When comparing responses pre- and post-BCG vaccination in the delayed vaccine group , there was no priming of mycobacterial IL-17 . Mycobacterial responses waned over 9 mo in those vaccinated at birth , leading to comparable mycobacterial immunity in both groups at 9 mo of age . Overall , these data suggest that vaccination at birth induces a broad Th1/Th2/IL-17/Treg mycobacterial response but the Th1/Th-17 response was reduced when delaying the vaccine . The evidence did not suggest that mycobacterial specific naturally occurring Tregs accounted for this attenuated immunogenicity ABSTRACT Immune responses to exogenous antigens in infant experimental animals display various degrees of Th2 polarization . Preliminary evidence from small human studies suggest a similar age-dependent response pattern to vaccines , but detailed investigations on vaccine immunity during infancy have not yet been undertaken . We report below the results of a comprehensive prospect i ve study on responses to the tetanus component of the diphtheria , tetanus , acellular pertussis ( DTaP ) vaccine in a cohort of 55 healthy children , employing peripheral blood mononuclear cells ( P BMC ) collected at the 2- , 4- , and 6-month vaccinations and at 12 months . Antigen-specific production of interleukin-4 ( IL-4 ) , IL-5 , IL-6 , IL-9 , IL-10 , IL-13 , and gamma interferon ( IFN-γ ) was determined at each sample point , in parallel with polyclonal ( phytohemagglutinin PHA-induced ) cytokine responses . Our results indicate early and persistent Th2 responses to the vaccine , in contrast to a more delayed and transient pattern of IFN-γ production . This initial disparity between the Th1 and Th2 components of the vaccine response was mirrored by patterns of polyclonally induced cytokine production , suggesting that the delayed maturation of the Th1 component of the vaccine response during infancy is secondary to developmental processes occurring within the overall Th cell system Recent epidemiologic data have indicated that adults are the most important reservoir that transmit pertussis to children . However , conventional whole cell pertussis vaccine is contraindicated in adults and children over 7 years of age because of the unacceptably high rate of adverse reactions . The aim of this study is to evaluate the specific cellular immune responses and adverse reactions to a less reactogenic acellular pertussis vaccine in adult volunteers . Eighty healthy medical personnel in Chang Gung Children 's Hospital were enrolled . Volunteers in each group received : ( 1 ) Td + full strength acellular pertussis vaccine ( PT , 1 microgram/0.5 ml ; FHA , 4 micrograms/0.5 ml ) ; ( 2 ) Td + half strength acellular pertussis vaccine ; ( 3 ) Td alone .  Lymphocyte phenotypic analysis , antigen-specific antibody titers , antigen-specific proliferative response and cytokine levels were evaluated before and 1 month after vaccination . Our data revealed : ( 1 ) the adverse reactions were minimal ; ( 2 ) phenotypic analysis showed no non-specific activation of helper T or memory T cell after vaccination ; ( 3 ) both PT and FHA-specific antibody titers increased significantly after vaccination , ( 4 ) PT antigens had a mitogenic effect on cord blood mon 
    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 / Objectives : Vitamin D mediates immunomodulatory functions , and its deficiency has been associated with an increased prevalence of immunological diseases . The supplementation of vitamin D might be therapeutically beneficial , for example , in lupus erythematosus patients . However , its affect on established recall immune responses is undefined . Subjects/ Methods : In all , 32 individuals were r and omized in a placebo controlled , double-blind setting , and received vitamin D ( daily 2000 IU ) for 10 weeks followed by tetanus toxoid ( TT ) booster immunization . Results : During vitamin D supplementation the median 25-hydroxyvitamin D serum concentration increased to 80.3 nM , which as expected decreased in the placebo group to 29.1 nM during the ultraviolet-deprived winter months . The TT-specific immunoglobulin G ( IgG ) boost efficiency was marginal higher in the vitamin D group ( P=0.04 ) . The increase of the 25-hydroxyvitamin D levels correlated with the increase of TT – IgG serum concentrations . The induction of specific serum IgA and specific antibody secreting cells was comparable between both groups . Accordingly , the TT-specific and polyclonally triggered T-cell cytokine profiles were stable as well . Conclusions : Vitamin D supplementation was successful and booster immunization induced efficiently specific antibodies titers Abstract Objective To study the effect of vaccination on  mortality before 2 years of age in a developing country . Design Prospect i ve cohort study . Setting Rural communities in Burkina Faso . Participants 9085 children born in the study area between 1985 and 1993 . Main outcome measure Child death rate . Results Mortality before 2 years of age was lower in children who had been vaccinated : those vaccinated with BCG only had significantly lower mortality ( risk ratio for vaccinated v unvaccinated children 0.37 , 95 % confidence interval 0.29 to 0.48 ) as did those vaccinated with diphtheria , tetanus , and pertussis only ( 0.24 , 0.13 to 0.43 ) . The second dose of diphtheria , tetanus , and pertussis was not associated with lower mortality ( 0.80 , 0.58 to 1.12 ) . Conclusion Vaccination with diphtheria , tetanus , and pertussis as well as BCG is associated with better survival of children up to 2 years of age OBJECTIVES To evaluate the safety and immunogenicity of an additional birth dose of diphtheria , tetanus , and acellular pertussis vaccine ( DTaP ) . STUDY DESIGN Fifty infants between 2 to 14 days of age were r and omly assigned to receive either DTaP and hepatitis B vaccines ( experimental ) or hepatitis B alone ( control ) at birth . At 2 , 4 , 6 , and 17 months of age , DTaP and routine vaccines were administered to both groups . Safety data were collected after each dose , and sera were obtained at birth , 6 , 7 , 17 , and 18 months . Immune responses to pertussis toxin , filamentous hemagglutinin , pertactin , and fimbriae were measured by enzyme-linked immunosorbent assay ; responses to other vaccines were assessed . RESULTS No differences were seen between the 2 groups in either local or systemic reactions ; all vaccines were well tolerated . Compared with the control group , infants in the experimental group demonstrated significantly lower geometric mean antibody concentrations for pertussis toxin and pertactin 6 , 7 , and 18 months , for fimbrae at 6 , 7 , 17 , and 18 months , and for FHA at 18 months , and lower geometric mean antibody concentrations for diphtheria at 7 months . Immune responses to all other vaccine antigens were comparable . CONCLUSION Administration of an additional dose of DTaP at birth was safe but was associated with a significantly lower response to diphtheria and 3 of 4 pertussis antigens compared with controls Background / Objectives : Vitamin E is an essential fat-soluble vitamin that has been shown to induce favorable effects on animal and human immune systems . The objective of this study was to assess the effects of tocotrienol-rich fraction ( TRF ) supplementation on immune response following tetanus toxoid ( TT ) vaccine challenge in healthy female volunteers . Subjects/ Methods : In this double-blinded , placebo-controlled clinical trial , participants were r and omly assigned to receive either placebo ( control group ) or 400 mg of TRF ( study group ) supplementation daily . Over the 2-month period of the study , volunteers were asked to attend three clinical sessions ( that is , on days 0 , 28 and 56 ) and blood sample s were obtained from the volunteers during the follow-up . On day 28 , all volunteers were also vaccinated with the TT vaccine ( 20 Lf ) intramuscularly . Results : The results from the clinical trial showed that TRF supplementation significantly increased the total vitamin E level in the plasma of the TRF-supplemented volunteers compared with the placebo group , indicating overall compliance . Volunteers supplemented with TRF showed a significantly ( P<0.05 ) enhanced production of interferon-γ and interleukin (IL)-4 by the mitogen or TT-stimulated leukocytes compared with the control group . Volunteers from the TRF group produced significantly ( P<0.05 ) lower amounts of IL-6 compared with the placebo group . Anti-TT IgG production was also significantly ( P<0.05 ) augmented in the TRF-supplemented group compared with the placebo group . Conclusions : We conclude that TRF has immunostimulatory effects and potential clinical benefits to enhance immune response to vaccines BACKGROUND In most tuberculosis ( TB ) endemic countries , bacillus Calmette-Guérin ( BCG ) is usually given around birth to prevent severe TB in infants . The neonatal immune system is immature . Our hypothesis was that delaying BCG vaccination from birth to 10 weeks of age would enhance the vaccine-induced immune response . METHODS In a r and omized clinical trial , BCG was administered intradermally either at birth ( n=25 ) or at 10 weeks of age ( n=21 ) . Ten weeks after vaccination , and at 1 year of age , vaccine-specific CD4 and CD8 T cell responses were measured with a whole blood intracellular cytokine assay . RESULTS Infants who received delayed BCG vaccination demonstrated higher frequencies of BCG-specific CD4 T cells , particularly polyfunctional T cells co-expressing IFN-gamma , TNF-alpha and IL-2 , and most strikingly at 1 year of age . CONCLUSIONS Delaying BCG vaccination from birth to 10 weeks of age enhances the quantitative and qualitative BCG-specific T cell response , when measured at 1 year of age BACKGROUND Bacille Calmette-Guérin ( BCG ) is a strong T helper 1 incentive and , thus , may contribute to a decreased risk of T helper 2-dependent atopic disease . OBJECTIVE To investigate the natural course of specific immunoglobulin E ( IgE ) responses and atopic disease in  BCG-vaccinated and nonvaccinated children . PARTICIPANTS Seven hundred seventy-four children from a prospect ively followed birth cohort . OUTCOME MEASURES Physical examination and case history were performed at 3 , 6 , 12 , 18 , 24 , 36 , 48 , 60 , 72 , and 84 months of age . Total and specific serum IgE levels to 9 common inhalant and food allergens were determined ( CAP ; Pharmacia , Freiburg , Germany ) at 12 , 24 , 36 , 60 , 72 , and 84 months of age . Purified protein derivative ( PPD ) skin testing was performed at 84 months . RESULTS Period and lifetime prevalences of atopic dermatitis and recurrent wheezing tended to be lower in the BCG-vaccinated group early in life , whereas no such trend was found after the second birthday or for allergic rhinitis . The proportion of children remaining free of clinical manifestations tended to be higher in the BCG-vaccinated group but differences decreased over time . No statistically significant differences were found for total IgE levels ( median ) . Atopic sensitization tended to be lower among BCG-vaccinated children during the first 2 years of life . The diameter of the skin reaction to PPD did not correlate with total serum IgE. Clinical and serologic correlates of atopy were not significantly different between children with a skin test diameter of > /=5 mm and those with a smaller diameter . CONCLUSION These results do not support the hypothesis that BCG vaccination in early infancy is associated with a subsequently markedly decreased risk of atopic sensitization or allergy . In addition , PPD skin test reactivity was not impaired in atopic individuals Bacillus Camette-Guérin ( BCG ) vaccine is the only licensed vaccine against tuberculosis , yet its protective efficacy is highly variable between different geographical regions . We hypothesized that exposure to nontuberculous mycobacteria attenuates BCG immunogenicity by inducing mycobacterial-specific regulatory T cells ( Tregs ) . Gambian neonates were recruited at birth and r and omized to receive  BCG vaccination  either at birth or at 4 1/2 mo . Mycobacterial immune responses were assessed at birth , 4 1/2 , and 9 mo of age . At 4 1/2 mo of age the BCG naive individuals had detectable mycobacterial responses , including increased IL-10 production suggesting environmental priming . Vaccination at birth significantly enhanced Th1 , Th2 , IL-6 , IL-17 , and Treg responses in mycobacterial cultures at 4 1/2 mo compared with the BCG naive group . Analyzing results at 4 1/2 mo postvaccination revealed lower IFN-γ , IL-6 , and IL-17 responses in the delayed BCG vaccine group compared with those vaccinated at birth , but this did not relate to Treg levels prevaccination . When comparing responses pre- and post-BCG vaccination in the delayed vaccine group , there was no priming of mycobacterial IL-17 . Mycobacterial responses waned over 9 mo in those vaccinated at birth , leading to comparable mycobacterial immunity in both groups at 9 mo of age . Overall , these data suggest that vaccination at birth induces a broad Th1/Th2/IL-17/Treg mycobacterial response but the Th1/Th-17 response was reduced when delaying the vaccine . The evidence did not suggest that mycobacterial specific naturally occurring Tregs accounted for this attenuated immunogenicity ABSTRACT Immune responses to exogenous antigens in infant experimental animals display various degrees of Th2 polarization . Preliminary evidence from small human studies suggest a similar age-dependent response pattern to vaccines , but detailed investigations on vaccine immunity during infancy have not yet been undertaken . We report below the results of a comprehensive prospect i ve study on responses to the tetanus component of the diphtheria , tetanus , acellular pertussis ( DTaP ) vaccine in a cohort of 55 healthy children , employing peripheral blood mononuclear cells ( P BMC ) collected at the 2- , 4- , and 6-month vaccinations and at 12 months . Antigen-specific production of interleukin-4 ( IL-4 ) , IL-5 , IL-6 , IL-9 , IL-10 , IL-13 , and gamma interferon ( IFN-γ ) was determined at each sample point , in parallel with polyclonal ( phytohemagglutinin PHA-induced ) cytokine responses . Our results indicate early and persistent Th2 responses to the vaccine , in contrast to a more delayed and transient pattern of IFN-γ production . This initial disparity between the Th1 and Th2 components of the vaccine response was mirrored by patterns of polyclonally induced cytokine production , suggesting that the delayed maturation of the Th1 component of the vaccine response during infancy is secondary to developmental processes occurring within the overall Th cell system Recent epidemiologic data have indicated that adults are the most important reservoir that transmit pertussis to children . However , conventional whole cell pertussis vaccine is contraindicated in adults and children over 7 years of age because of the unacceptably high rate of adverse reactions . The aim of this study is to evaluate the specific cellular immune responses and adverse reactions to a less reactogenic acellular pertussis vaccine in adult volunteers . Eighty healthy medical personnel in Chang Gung Children 's Hospital were enrolled . Volunteers in each group received : ( 1 ) Td + full strength acellular pertussis vaccine ( PT , 1 microgram/0.5 ml ; FHA , 4 micrograms/0.5 ml ) ; ( 2 ) Td + half strength acellular pertussis vaccine ; ( 3 ) Td alone .  Lymphocyte phenotypic analysis , antigen-specific antibody titers , antigen-specific proliferative response and cytokine levels were evaluated before and 1 month after vaccination . Our data revealed : ( 1 ) the adverse reactions were minimal ; ( 2 ) phenotypic analysis showed no non-specific activation of helper T or memory T cell after vaccination ; ( 3 ) both PT and FHA-specific antibody titers increased significantly after vaccination , ( 4 ) PT antigens had a mitogenic effect on cord blood mon 
    Output:
    