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: OBJECTIVES In 1998 the World Health Organization ( WHO ) recommended the inclusion of Haemophilus influenza type B ( Hib ) conjugate vaccines in infant immunization programs , whenever in accordance with national priorities . GlaxoSmithKline Biologicals has developed a new pentavalent combined diphtheria-tetanus-whole cell pertussis-hepatitis B/Hib ( DTPw-HB/Hib ) vaccine containing 5 microg of polyribosylribitol phosphate ( PRP ) , and we assessed the immunogenicity and reactogenicity of primary and booster vaccination of healthy children with this new vaccine compared with a reference regimen consisting of the licensed DTPw-HB ( Tritanrix ) and Hib ( Hiberix ) vaccines given as simultaneous concomitant injections . METHODS We performed a r and omized , double-blind study from September 1998 to August 1999 to establish the immunogenicity and reactogenicity of primary and booster vaccination of healthy children with the new pentavalent combined DTPw-HB/Hib vaccine  given as a single injection , compared with the reference regimen . RESULTS Both vaccination regimens elicited excellent immune responses , with all subjects in both groups achieving seroprotective anti-PRP antibody concentrations of > or = 0.15 microg/mL one month after primary vaccination . The combined DTPw-HB/Hib vaccine was non-inferior to the licensed vaccines in terms of seroprotection/seropositivity/vaccine response rates for all antigen components . Persistence of antibodies against all study vaccine antigens up to the time of booster vaccination was comparable between groups , and a marked increase of all antibody concentrations was observed after the booster dose . Both vaccine regimens were similar in terms of their overall reactogenicity profiles . CONCLUSIONS Our results indicate that the new DTPw-HB/Hib pentavalent combination vaccine provides an efficient and reliable way of implementing WHO recommendations for controlling hepatitis B and Hib infections on a worldwide basis We evaluated the immunogenicity and reactogenicity of a new liquid pentavalent combination vaccine , which incorporates a diphtheria , tetanus and whole-cell pertussis vaccine ( DTP ) with Hib ( PRP-OMPC ) and hepatitis B vaccine ( HB ) , in a series of three studies involving 2156 infants . The vaccination schedule was 2 , 4 , 6 and 18 months for all studies . In addition , subjects in the third study also received a dose of monovalent hepatitis B vaccine  at birth . The principal study was a r and omised double blind trial of two separate , but concurrently administered vaccines in each of three groups : pentavalent vaccine [ DTP-Hib-HB ] plus placebo ( Group A , n=619 ) ; quadrivalent vaccine [ DTP-HB ] plus Hib vaccine ( Group B , n=620 ) ; and bivalent vaccine [ Hib-HB ] plus DTP ( Group C , n=226 ) . The second study ( Group D , n=231 ) was an open trial of three separate , but concurrently administered licensed control vaccines ( DTP , Hib and HB ) . The third study ( Group E , n=460 ) administered a dose of monovalent hepatitis B vaccine at birth followed by pentavalent vaccine as for Group A. Subjects were bled prior to the 2- and 18-month vaccinations , and a month after the 6- and 18-month vaccinations . A diary card was used to record subject temperatures and other systemic and local clinical signs for 7 days after each vaccination . The pentavalent vaccine , whether or not preceded by a birth dose of hepatitis B vaccine , was generally well tolerated at all administration times , and had a reactogenicity profile similar to that observed for licensed vaccine controls . Diphtheria and tetanus antibody levels were substantially above protective levels in all study groups . The anti-HBs responses ( % > or = 10 mIU/ml ) following the 6-month dose of vaccines were , respectively , for Groups A-E : 83.2 , 91.7 , 96.5 , 98.8 and 93.9 % , and following the 18-month doses : 87.9 , 97.5 , 98.8 , 98.8 and 92.8 % . Anti-PRP responses ( % > or = 1.0 microg/ml ) following the 6-month dose for Groups A-D were 86.0 , 90.5 , 91.2 , and 74.4 % , and after the 18-month dose for Groups A-E were 97.3 , 98.3 , 98.1 , 97.0 , and 99.5 % . Consistently higher geometric mean titres ( GMTs ) for pertussis antibodies to agglutinogens ( Agg2 , Agg3 ) and pertactin were recorded for the pentavalent vaccine compared to the licensed control vaccine , though they were somewhat lower for pertussigen ( PT ) . Except for the hepatitis B response , antibody responses induced by the pentavalent vaccine to all antigens with a schedule commencing at 2 months of age and completed at 18 months were equivalent to responses to the same antigens induced by the separate , but concurrently administered licensed control vaccines . A regimen of a birth dose of hepatitis B vaccine followed by pentavalent vaccine at 2 , 4 , 6 and 18 months was not countered by any clinical ly significant decrease in seroresponses This paper presents the results of four separate phase III trials , which assessed the immunogenicity and reactogenicity of DTPw-HBV/Hib 2.5 in comparison with licensed Tritanrix-Hep B ( GlaxoSmithKline Biologicals ) and Hiberix ( 10 microg PRP ) , given as separate or mixed injections ( 3 trials ) or with or without hepatitis B vaccine at birth ( 1 trial ) . The immunogenicity of DTPw-HBV/Hib 2.5 was non-inferior to the reference vaccine regimen in terms of seropositivity rates . The overall reactogenicity profile of DTPw-HBV/Hib 2.5 was also similar to that of the reference vaccine regimen . These results confirm the previously established immunogenicity and safety of reduced dose PRP conjugated vaccine regimens OBJECTIVE The aim of this open , multicenter , r and omized trial was to evaluate the immunogenicity and reactogenicity of a c and i date combined diphtheria-tetanus-acellular pertussis-hepatitis B virus-inactivated polio virus ( DTaP-HBV-IPV ) vaccine when given as either a mixed or as separate concomitant injections with Haemophilus influenzae type b ( Hib ) vaccine . STUDY DESIGN A total of 359 subjects were r and omized to receive either DTaP-HBV-IPV/Hib ( mixed administration - 180 subjects ) or DTaP-HBV-IPV + Hib ( separate administration in opposite limbs - 179 subjects ) at 2 , 3 , and 4 months of age . RESULTS After vaccination , seroprotective antibody concentrations against diphtheria , tetanus , hepatitis B , and polio viruses and a high ( > or = 97 % ) pertussis vaccine response were seen in almost all study participants . All subjects except one in the mixed administration group had postvaccination Hib anti-PRP antibody concentrations > or = 0.15 microg/mL. Of subjects in the mixed and separate group , 77.2 % ( geometric mean antibody concentration , 2 . 62 microg/mL ) and 88.6 % ( geometric mean antibody concentration , 4.45 microg/mL ) had Hib anti-PRP concentrations > or = 1 microg/mL , respectively . The addition of the Hib component to the 5-component vaccine did not increase the incidence of local or general reactions . CONCLUSION Both administrations of the c and i date vaccine were found to be safe , immunogenic , and well tolerated . Although anti-PRP geometric mean antibody concentrations and the percent of subjects achieving the 1 microg/mL seroprotective level were lower after the mixed administration , they were in the range seen with monovalent Hib vaccines or with other DTaP-based/Hib combinations licensed in some European countries . Therefore both administrations have the potential to simplify childhood immunization OBJECTIVE The DTPw-HB/Hib pentavalent combination vaccine has been developed following recommendations of the World Health Organization for the introduction of hepatitis B ( HB ) and Haemophilus influenzae type b ( Hib ) vaccines into routine childhood vaccination programs . The objectives of this study were to : 1 ) analyze the immunogenicity and the reactogenicity of the DTPw-HB/Hib pentavalent combination vaccine in comparison to separate injections of DTPw-HB and Hib vaccines as primary vaccination in a group of children who had received a dose of HB vaccine at birth and 2 ) in the second year of life to assess the antibody persistence as well as the response to a DTPw-HB/Hib or DTPw/Hib booster . METHODS In the first part of the study ( primary -vaccination stage ) , conducted in 1998 - 1999 , we analyzed the immunogenicity and reactogenicity of the DTPw-HB/Hib combination vaccine in comparison to separate injections of DTPw-HB and Hib vaccines as primary vaccination at 2 , 4 , and 6 months of age in 207 Costa Rican children who had received a dose of HB vaccine at birth . Later , in the booster-vaccination stage of the study , in 1999 - 2000 , in a subset of the children ( 69 toddlers , now 15 - 18 months old ) , antibody persistence was measured , and response to a DTPw-HB/Hib or DTPw/Hib booster was also assessed . RESULTS In both primary -vaccination groups , at least 97.5 % of the infants reached protective levels of antibodies ( seropositivity ) against the antigens employed in the vaccines . The DTPw-HB/Hib pentavalent combination vaccine did not result in more local reactions than did the DTPw-HB vaccine alone , and , in terms of general reactions , there was no clinical ly significant difference between the combination or separate injections , and with the pentavalent vaccine having the benefit of needing one less injection . Nine months after the third dose of the primary -vaccination course , antibody persistence was similar in both groups , with over 93 % of children still having protective/seropositive titers for Hib , HB , and tetanus and about 50 % for diphtheria and Bordetella pertussis . At 15 months of age , virtually all the toddlers responded with a strong boost response to all the vaccine antigens , whether they received the DTPw-HB/Hib pentavalent vaccine or the DTPw/Hib vaccine as a booster . Both booster regimens were equally well tolerated , indicating that up to five doses of the HB vaccine can be given without impact on safety . CONCLUSIONS Our study confirms that the DTPw-HB/Hib pentavalent vaccine is highly immunogenic as a primary vaccination in children who received an HB vaccine at birth , with the pentavalent combination inducing both persisting immunity and boostable memory . The pentavalent vaccine was safe both for primary and booster vaccinations . Thus , this study in Costa Rican infants supports the routine use of the pentavalent DTPw-HB/Hib vaccine as part of childhood vaccination programs in Latin America and the Caribbean This double-blind , r and omised study was performed to assess the immunogenicity and reactogenicity of three lots of a quadrivalent diphtheria-tetanus-acellular pertussis-hepatitis B vaccine ( DTPa-HBV ) co-administered with three lots of Haemophilus influenzae type b conjugate ( Hib ) vaccine in one injection , as a primary vaccination course in healthy infants at 2 , 4 and 6 months of age . 269 infants ( 8 - 11 weeks of age ) were r and omly allocated to three groups to receive DTPa-HBV/Hib vaccines , concomitantly with oral polio vaccine .  Blood sample s for antibody determinations were taken before vaccination and 1 month after the third dose in 262 subjects . Local and general symptoms were recorded by parents on diary cards . All vaccinees had post-vaccination protective anti-D and anti-T ( > or = 0.1 IU ml-1 ) antibodies , and 98 % had protective anti-HBs antibody titres ( > or = 10 mIU ml-1 ) . There were no statistically significant differences between groups in post-vaccination anti-D , anti-T , anti-HBs antibody geometric mean titres ( GMT ) , these being 3.49 IU ml-1 , 5.92 IU ml-1 and 1109 mIU ml-1 , respectively . All subjects responded to three pertussis components , i.e. pertussis toxin ( PT ) , filamentous haemagglutinin ( FHA ) and pertactin ( PRN 
    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: OBJECTIVES In 1998 the World Health Organization ( WHO ) recommended the inclusion of Haemophilus influenza type B ( Hib ) conjugate vaccines in infant immunization programs , whenever in accordance with national priorities . GlaxoSmithKline Biologicals has developed a new pentavalent combined diphtheria-tetanus-whole cell pertussis-hepatitis B/Hib ( DTPw-HB/Hib ) vaccine containing 5 microg of polyribosylribitol phosphate ( PRP ) , and we assessed the immunogenicity and reactogenicity of primary and booster vaccination of healthy children with this new vaccine compared with a reference regimen consisting of the licensed DTPw-HB ( Tritanrix ) and Hib ( Hiberix ) vaccines given as simultaneous concomitant injections . METHODS We performed a r and omized , double-blind study from September 1998 to August 1999 to establish the immunogenicity and reactogenicity of primary and booster vaccination of healthy children with the new pentavalent combined DTPw-HB/Hib vaccine  given as a single injection , compared with the reference regimen . RESULTS Both vaccination regimens elicited excellent immune responses , with all subjects in both groups achieving seroprotective anti-PRP antibody concentrations of > or = 0.15 microg/mL one month after primary vaccination . The combined DTPw-HB/Hib vaccine was non-inferior to the licensed vaccines in terms of seroprotection/seropositivity/vaccine response rates for all antigen components . Persistence of antibodies against all study vaccine antigens up to the time of booster vaccination was comparable between groups , and a marked increase of all antibody concentrations was observed after the booster dose . Both vaccine regimens were similar in terms of their overall reactogenicity profiles . CONCLUSIONS Our results indicate that the new DTPw-HB/Hib pentavalent combination vaccine provides an efficient and reliable way of implementing WHO recommendations for controlling hepatitis B and Hib infections on a worldwide basis We evaluated the immunogenicity and reactogenicity of a new liquid pentavalent combination vaccine , which incorporates a diphtheria , tetanus and whole-cell pertussis vaccine ( DTP ) with Hib ( PRP-OMPC ) and hepatitis B vaccine ( HB ) , in a series of three studies involving 2156 infants . The vaccination schedule was 2 , 4 , 6 and 18 months for all studies . In addition , subjects in the third study also received a dose of monovalent hepatitis B vaccine  at birth . The principal study was a r and omised double blind trial of two separate , but concurrently administered vaccines in each of three groups : pentavalent vaccine [ DTP-Hib-HB ] plus placebo ( Group A , n=619 ) ; quadrivalent vaccine [ DTP-HB ] plus Hib vaccine ( Group B , n=620 ) ; and bivalent vaccine [ Hib-HB ] plus DTP ( Group C , n=226 ) . The second study ( Group D , n=231 ) was an open trial of three separate , but concurrently administered licensed control vaccines ( DTP , Hib and HB ) . The third study ( Group E , n=460 ) administered a dose of monovalent hepatitis B vaccine at birth followed by pentavalent vaccine as for Group A. Subjects were bled prior to the 2- and 18-month vaccinations , and a month after the 6- and 18-month vaccinations . A diary card was used to record subject temperatures and other systemic and local clinical signs for 7 days after each vaccination . The pentavalent vaccine , whether or not preceded by a birth dose of hepatitis B vaccine , was generally well tolerated at all administration times , and had a reactogenicity profile similar to that observed for licensed vaccine controls . Diphtheria and tetanus antibody levels were substantially above protective levels in all study groups . The anti-HBs responses ( % > or = 10 mIU/ml ) following the 6-month dose of vaccines were , respectively , for Groups A-E : 83.2 , 91.7 , 96.5 , 98.8 and 93.9 % , and following the 18-month doses : 87.9 , 97.5 , 98.8 , 98.8 and 92.8 % . Anti-PRP responses ( % > or = 1.0 microg/ml ) following the 6-month dose for Groups A-D were 86.0 , 90.5 , 91.2 , and 74.4 % , and after the 18-month dose for Groups A-E were 97.3 , 98.3 , 98.1 , 97.0 , and 99.5 % . Consistently higher geometric mean titres ( GMTs ) for pertussis antibodies to agglutinogens ( Agg2 , Agg3 ) and pertactin were recorded for the pentavalent vaccine compared to the licensed control vaccine , though they were somewhat lower for pertussigen ( PT ) . Except for the hepatitis B response , antibody responses induced by the pentavalent vaccine to all antigens with a schedule commencing at 2 months of age and completed at 18 months were equivalent to responses to the same antigens induced by the separate , but concurrently administered licensed control vaccines . A regimen of a birth dose of hepatitis B vaccine followed by pentavalent vaccine at 2 , 4 , 6 and 18 months was not countered by any clinical ly significant decrease in seroresponses This paper presents the results of four separate phase III trials , which assessed the immunogenicity and reactogenicity of DTPw-HBV/Hib 2.5 in comparison with licensed Tritanrix-Hep B ( GlaxoSmithKline Biologicals ) and Hiberix ( 10 microg PRP ) , given as separate or mixed injections ( 3 trials ) or with or without hepatitis B vaccine at birth ( 1 trial ) . The immunogenicity of DTPw-HBV/Hib 2.5 was non-inferior to the reference vaccine regimen in terms of seropositivity rates . The overall reactogenicity profile of DTPw-HBV/Hib 2.5 was also similar to that of the reference vaccine regimen . These results confirm the previously established immunogenicity and safety of reduced dose PRP conjugated vaccine regimens OBJECTIVE The aim of this open , multicenter , r and omized trial was to evaluate the immunogenicity and reactogenicity of a c and i date combined diphtheria-tetanus-acellular pertussis-hepatitis B virus-inactivated polio virus ( DTaP-HBV-IPV ) vaccine when given as either a mixed or as separate concomitant injections with Haemophilus influenzae type b ( Hib ) vaccine . STUDY DESIGN A total of 359 subjects were r and omized to receive either DTaP-HBV-IPV/Hib ( mixed administration - 180 subjects ) or DTaP-HBV-IPV + Hib ( separate administration in opposite limbs - 179 subjects ) at 2 , 3 , and 4 months of age . RESULTS After vaccination , seroprotective antibody concentrations against diphtheria , tetanus , hepatitis B , and polio viruses and a high ( > or = 97 % ) pertussis vaccine response were seen in almost all study participants . All subjects except one in the mixed administration group had postvaccination Hib anti-PRP antibody concentrations > or = 0.15 microg/mL. Of subjects in the mixed and separate group , 77.2 % ( geometric mean antibody concentration , 2 . 62 microg/mL ) and 88.6 % ( geometric mean antibody concentration , 4.45 microg/mL ) had Hib anti-PRP concentrations > or = 1 microg/mL , respectively . The addition of the Hib component to the 5-component vaccine did not increase the incidence of local or general reactions . CONCLUSION Both administrations of the c and i date vaccine were found to be safe , immunogenic , and well tolerated . Although anti-PRP geometric mean antibody concentrations and the percent of subjects achieving the 1 microg/mL seroprotective level were lower after the mixed administration , they were in the range seen with monovalent Hib vaccines or with other DTaP-based/Hib combinations licensed in some European countries . Therefore both administrations have the potential to simplify childhood immunization OBJECTIVE The DTPw-HB/Hib pentavalent combination vaccine has been developed following recommendations of the World Health Organization for the introduction of hepatitis B ( HB ) and Haemophilus influenzae type b ( Hib ) vaccines into routine childhood vaccination programs . The objectives of this study were to : 1 ) analyze the immunogenicity and the reactogenicity of the DTPw-HB/Hib pentavalent combination vaccine in comparison to separate injections of DTPw-HB and Hib vaccines as primary vaccination in a group of children who had received a dose of HB vaccine at birth and 2 ) in the second year of life to assess the antibody persistence as well as the response to a DTPw-HB/Hib or DTPw/Hib booster . METHODS In the first part of the study ( primary -vaccination stage ) , conducted in 1998 - 1999 , we analyzed the immunogenicity and reactogenicity of the DTPw-HB/Hib combination vaccine in comparison to separate injections of DTPw-HB and Hib vaccines as primary vaccination at 2 , 4 , and 6 months of age in 207 Costa Rican children who had received a dose of HB vaccine at birth . Later , in the booster-vaccination stage of the study , in 1999 - 2000 , in a subset of the children ( 69 toddlers , now 15 - 18 months old ) , antibody persistence was measured , and response to a DTPw-HB/Hib or DTPw/Hib booster was also assessed . RESULTS In both primary -vaccination groups , at least 97.5 % of the infants reached protective levels of antibodies ( seropositivity ) against the antigens employed in the vaccines . The DTPw-HB/Hib pentavalent combination vaccine did not result in more local reactions than did the DTPw-HB vaccine alone , and , in terms of general reactions , there was no clinical ly significant difference between the combination or separate injections , and with the pentavalent vaccine having the benefit of needing one less injection . Nine months after the third dose of the primary -vaccination course , antibody persistence was similar in both groups , with over 93 % of children still having protective/seropositive titers for Hib , HB , and tetanus and about 50 % for diphtheria and Bordetella pertussis . At 15 months of age , virtually all the toddlers responded with a strong boost response to all the vaccine antigens , whether they received the DTPw-HB/Hib pentavalent vaccine or the DTPw/Hib vaccine as a booster . Both booster regimens were equally well tolerated , indicating that up to five doses of the HB vaccine can be given without impact on safety . CONCLUSIONS Our study confirms that the DTPw-HB/Hib pentavalent vaccine is highly immunogenic as a primary vaccination in children who received an HB vaccine at birth , with the pentavalent combination inducing both persisting immunity and boostable memory . The pentavalent vaccine was safe both for primary and booster vaccinations . Thus , this study in Costa Rican infants supports the routine use of the pentavalent DTPw-HB/Hib vaccine as part of childhood vaccination programs in Latin America and the Caribbean This double-blind , r and omised study was performed to assess the immunogenicity and reactogenicity of three lots of a quadrivalent diphtheria-tetanus-acellular pertussis-hepatitis B vaccine ( DTPa-HBV ) co-administered with three lots of Haemophilus influenzae type b conjugate ( Hib ) vaccine in one injection , as a primary vaccination course in healthy infants at 2 , 4 and 6 months of age . 269 infants ( 8 - 11 weeks of age ) were r and omly allocated to three groups to receive DTPa-HBV/Hib vaccines , concomitantly with oral polio vaccine .  Blood sample s for antibody determinations were taken before vaccination and 1 month after the third dose in 262 subjects . Local and general symptoms were recorded by parents on diary cards . All vaccinees had post-vaccination protective anti-D and anti-T ( > or = 0.1 IU ml-1 ) antibodies , and 98 % had protective anti-HBs antibody titres ( > or = 10 mIU ml-1 ) . There were no statistically significant differences between groups in post-vaccination anti-D , anti-T , anti-HBs antibody geometric mean titres ( GMT ) , these being 3.49 IU ml-1 , 5.92 IU ml-1 and 1109 mIU ml-1 , respectively . All subjects responded to three pertussis components , i.e. pertussis toxin ( PT ) , filamentous haemagglutinin ( FHA ) and pertactin ( PRN 
    Output:
    