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Background: This study investigated the immunogenicity and safety of a fully liquid, hexavalent, diphtheria (D)-tetanus (T)-whole-cell pertussis (wP)-inactivated poliovirus (IPV)-hepatitis B (HB)- Haemophilus influenzae b (PRP-T) vaccine compared to licensed DTwP-HB-PRP~T, IPV, and bivalent oral poliovirus (bOPV) vaccines following co-administration with other pediatric vaccines [pneumococcal conjugate vaccine (PCV13) and rotavirus vaccine]., Methods: Phase III, randomized, open-label study in Thailand. Healthy infants received DTwP-IPV-HB-PRP~T at 2, 4 and 6 months of age (N = 228), or DTwP-HB-PRP~T and bOPV (2, 4 and 6 months of age) and IPV (4 months of age) (N = 231). All participants received PCV13 (2, 4 and 6 months of age) and rotavirus vaccine (2 and 4 months of age). Immunogenicity for all antigens was assessed using validated assays, and noninferiority post-third dose was evaluated for anti-D, anti-T, anti-pertussis [anti-pertussis toxin (anti-PT) and anti-fimbriae 2/3 (anti-FIM)], anti-polio 1, 2, 3, anti-HB, and anti-PRP~T. Safety was assessed using parental reports., Results: Noninferiority was demonstrated for each antigen, and overall noninferiority of DTwP-IPV-HB-PRP~T versus DTwP-HB-PRP~T+bOPV+IPV was concluded. Similarity in each group was observed for the GMC ratio for antirotavirus antibodies (20.9 and 17.3, respectively) and anti-PCV13 antibodies (range: 8.46-32.6 and 7.53-33.1, respectively). Two serious adverse events were related to DTwP-IPV-HB-PRP~T (febrile convulsion and acute febrile illness) and 1 was related to DTwP-HB-PRP~T+bOPV+IPV (febrile seizure), but overall there were no safety concerns with similar rates of participants experiencing solicited (99.1% and 98.3%) and unsolicited (19.3% and 19.5%) adverse events in each group., Conclusions: This study confirmed the suitability of DTwP-IPV-HB-PRP~T primary series vaccination in combination with rotavirus and PCV13 vaccines., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Anti-hepatitis B (HBs) antibody persistence and hepatitis B challenge were evaluated at 6 years of age following vaccination of fully liquid DTaP-IPV-HB-PRP~T or reconstituted DTaP-IPV-HB//PRP~T at 3, 5, 11-12 months of age. At 6 years, 53.8% and 73.5% had seroprotective anti-HBs antibodies (≥10 mIU/mL), increasing to 96.7% and 95.9% postchallenge, confirming a strong anamnestic response in primed vaccinees.

Globally, infant hepatitis B virus (HBV) immunization programs are markedly reducing the rate of chronic HBV infections among children <5 years of age. Desirable improvements include increased birth dose coverage and better prevention of perinatal HBV transmission. Follow-up studies show that by the teenage years most of those immunized as infants have lost circulating anti-HBs antibody and some fail to respond to challenge HBV vaccination, implying loss of protection from infection. With high exposure to HBV, such individuals can develop breakthrough HBV infection but this rarely leads to chronic infection, the main goal of prevention programs. While longer-term follow-up studies into adulthood are needed, current evidence does not support a need for booster immunization of otherwise healthy teens or young adults.

To support a fully liquid, diphtheria (D)-tetanus (T)-acellular pertussis (aP)-inactivated poliovirus (IPV)-hepatitis B (HB)-Haemophilus influenzae b (PRP-T) vaccine in Europe using a 2, 3, 4 month primary series and a booster at 11-15 months of age. Phase III, randomized, observer-blind studies in Germany and the Czech Republic. Participants who had not received HB vaccine were randomized to a 2, 3, 4 month primary series of DTaP-IPV-HB-PRP-T (group 1; N = 266) or a reconstituted DTaP-HB-IPV//PRP-T comparator (group 2; N = 263) and a booster of the same vaccine. Pneumococcal vaccine (PCV13) and rotavirus vaccine were coadministered at 2, 3, 4 months, and the booster was coadministered with PCV13. Noninferiority (group 1 versus group 2) was tested postprimary series for seroprotection rates (anti-HB and anti-PRP) and vaccine response rates (anti-pertussis toxin and anti-filamentous hemagglutinin). Safety was assessed by parental reports. Noninferiority was demonstrated with the lower bound of the 95% confidence interval for the difference (group 1 to group 2) being > -10% for each comparison. Primary series immune responses were high for all antigens and similar in each group. Prebooster antibody persistence was good, and there was a strong anamnestic response, both being similar for the investigational and control vaccines. Responses to PCV13 and rotavirus vaccine were similar in each group. There were no safety concerns. These data support the use of the DTaP-IPV-HB-PRP-T vaccine in a 2, 3, 4 month schedule without a birth dose of HB vaccine, with a booster dose in the second year of life administered with routine childhood vaccines.

To evaluate protective antibody levels against hepatitis B surface antigen in HIV-infected and HIV-uninfected Kenyan children, this study enrolled 531 children. In the HIV-infected group, only 18.3% had protective hepatitis B surface antigen compared with 74.4% in the HIV-uninfected group (P < 0.0001). Perhaps HIV-infected children should be immunized differently.

Background: Hexavalent diphtheria-tetanus-acellular pertussis-inactivated poliovirus-hepatitis B-Haemophilus influenzae type b (DTaP-IPV-HB-PRP-T)-containing vaccines are increasingly the standard of care. This study evaluated the primary series (NCT01177722) and booster (NCT01444781) of a fully liquid DTaP-IPV-HB-PRP-T vaccine in Latin America., Methods: Infants (N = 1375) received hepatitis B vaccine at birth and were randomized to one of 3 batches of the investigational DTaP-IPV-HB-PRP-T or licensed control vaccine (DTaP-HB-IPV//PRP-T) at 2-4 to 6 months of age, coadministered with 7-valent pneumococcal conjugate vaccine (PCV7) (2-4-6 months) and rotavirus vaccine (2-4 months). A booster of either DTaP-IPV-HB-PRP-T or control was given at 12-24 months, coadministered with PCV7. Immunogenicity was assessed by validated assays and safety from parental reports., Results: Primary series seroprotection and vaccine response rates were equivalent for DTaP-IPV-HB-PRP-T batches. For pooled batches, noninferiority to the control vaccine was demonstrated for each antigen. There were no descriptive differences in antibody persistence or booster response between DTaP-IPV-HB-PRP-T and the control. The booster responses to either vaccine following DTaP-IPV-HB-PRP-T primary series or to DTaP-IPV-HB-PRP-T following a control vaccine primary series were similar. The anti-aP component (filamentous hemagglutinin [FHA] and pertussis toxin [PT]) vaccine response and anti-Haemophilus influenzae type b (PRP) series seroprotection (≥0.15 µg/mL) rates were ≥73.0% after 2 primary series doses. Antipyretics had no effect on the immune response, and an extra (oral) polio vaccination had no effect on the antipolio booster response. Responses to PCV7 and rotavirus vaccine were similar for each coadministration. There were no safety concerns observed with any vaccine., Conclusions: These results confirm the suitability of the fully liquid DTaP-IPV-HB-PRP-T vaccine for primary and booster vaccination of infants.

Background: HIV infection may alter immunologic response and the establishment of immune memory to infant hepatitis B virus (HBV) vaccination. This study aimed to determine the need to revaccinate perinatally HIV-infected Thai adolescents., Methods: Cross-sectional serologic tests for HBV, including hepatitis B surface antigen, anti-hepatitis B surface antibody (anti-HBs) and anti-hepatitis B core antibody (anti-HBc), were performed in perinatally HIV-infected adolescents. Adolescents having anti-HBs <100 mIU/mL with negative anti-HBc and immune reconstitution from highly active antiretroviral therapy (HAART) were revaccinated using regular (10 μg) 3-dose schedule given intramuscularly at 0-, 2- and 6-month intervals., Results: Of 193 adolescents who received 3-dose infant HBV vaccination, 6 were receiving HAART during vaccination, median (interquartile range) current age 14.5 (11.7-16.2) years, 7 (3.6%) had positive anti-HBc (indicating breakthrough infection), of which 4 (2%) had positive hepatitis B surface antigen (indicating chronic infection). Twenty-two (11.4%) adolescents had protective anti-HBs concentration >10 mIU/mL. Of 164 revaccinated adolescents, 142 (86.6%) had HIV viral load <40 copies/mL. Anti-HBs seroconversion rates >10 mIU/mL were 58.0% (94/162) after the first dose and 97.5% (158/162) after the third dose of revaccination. Forty-five (28%) subjects responded to the first dose with anti-HBs antibody ≥100 mIU/mL had a shorter median duration with CD4 count <15% than their counterparts (6.2 vs. 11.1 months; P = 0.049)., Conclusions: Only half of perinatally HIV-infected adolescents were able to elicit anti-HBs response with a single-dose HBV vaccine. Revaccination with 3-dose schedule is required in perinatally HIV-infected adolescents who did not initiate HAART at the time of infant vaccination.

Background: The Advisory Committee on Immunization Practices (ACIP) recommends a 4-dose vaccination schedule for preterm low birth weight infants (<2 kg) and a 3-dose vaccination schedule for preterm infants (≥2 kg) born to hepatitis B surface antigen (HBsAg)-positive mothers. However, data remain limited for these high-risk infants, and the optimal dosing schedule in Asia is not well established., Aim: The aim of this study was to evaluate the serologic vaccine responses in preterm infants born to HBsAg-positive mothers using current vaccination guidelines., Methods: Preterm babies of gestation less than 37 completed weeks born to HBsAg-positive mothers were prospectively recruited during 6 years (June 2009 to December 2015) and retrospectively recruited via convenience sampling in 2 years (June 2013 to April 2015) in 2 tertiary pediatric centers. The preterm infants were given 4 or 3 vaccine doses as per ACIP 2005 guidelines. Vaccine response was defined as achieving hepatitis B surface antibody values of >10 IU/L [Abbott Architect (Abbott Laboratories, Chicago, IL)] at 9 months of chronologic age., Results: A total of 24 preterm infants were recruited. Four had a birth weight <2 kg. Of 23 surviving infants, all were negative for HBsAg. One baby (4.5%) did not achieve adequate vaccine response. All 4 infants with birth weight <2 kg achieved seroprotective values., Conclusion: The current ACIP-recommended vaccination schedule results in adequate antibody responses in preterm infants of HBsAg-positive mothers.

Background: Hepatitis B virus (HBV) vaccination programs generally target infants to prevent chronic HBV infection and/or preadolescents to reduce transmission in adulthood. To assess whether infant HBV immunization can potentially accomplish both objectives, we measured residual immunity 10-16 years after vaccination in Canadian children., Methods: A prospective, parallel group, single center study enrolled adolescents given HBV vaccine at 2, 4 and 6 months of age. Exclusion criteria included prior HBV infection and additional vaccinations. At follow-up anti-HBs testing, participants were 10-11 or 15-16 years old; those with <12 mIU/mL anti-HBs by the assay used were challenged with HBV vaccine to assess immune memory-based responsiveness., Results: A total of 137 tested participants were 10-11 and 213 were 15-16 years old, respectively; none had evidence of prior HBV infection. At baseline, 78% of younger and 64% of older participants had <12 mIU/mL anti-HBs (P = 0.006) and were challenged with vaccine: 103/106 (97.2%) younger and 123/135 (91.1%) older participants developed ≥12 mIU/mL anti-HBs (P = 0.06), with geometric mean antibody concentration of 590 (95% confidence interval: 473-737) and 319 mIU/mL (95% confidence interval: 229-445; P = 0.004), respectively. Immune memory loss may have occurred in 3 younger (2.2%) and 12 older children (5.6%; P = 0.06) who were nonresponsive to first but not second vaccine challenge., Conclusions: After HBV vaccination at 2, 4 and 6 months of age, most adolescents had little or no residual antibody but nearly all responded to HBV challenge, confirming immune memory persistence. However, anamnestic responses were weaker in 15- to 16-year olds and lost in some. Booster responses in 10- to 11-year olds were vigorous in comparison. Extended evaluation of protection is warranted.

Background: Booster doses could play a major role in no responders or low responders to primary hepatitis B (HB) vaccine. Planed time point for hepatitis A vaccination in China provides a good opportunity to carry out HB booster dose by using combined hepatitis A and B vaccine., Methods: A randomized, double-blinded clinical trial was conducted to compare the immunogenicity and safety of toddlers 18-24 months of age receiving 3 different vaccination regimens: 2 doses of inactivated hepatitis A vaccine (group 1), 1 dose of inactivated hepatitis A vaccine plus 1 dose of combined hepatitis A and B vaccine (group 2) or 2 doses of combined hepatitis A and B vaccine (group 3)., Results: All 3 groups showed 100% seroprotection for antihepatitis A virus antibody after vaccination. Seroprotection rate for anti-HB antibody before vaccination ranged from 79.5% to 92.9% in the 3 groups. After second inoculation, anti-HBs seroprotection increased from 92.9% to 100% in group 2 with postvaccination geometric mean concentration (GMC) of 2258.3 mIU/mL and from 79.5% to 98.9% in group 3 with postvaccination GMC of 2055.3 mIU/mL. The adverse events were not statistically different among groups (P = 0.345)., Conclusions: Combined hepatitis A and B vaccine could stimulate high level of both antihepatitis A virus and anti-HBs antibodies and not increase adverse events, providing a new choice for HB booster.

Background: Combination vaccines simplify vaccination visits and improve coverage and timeliness. Diphtheria-tetanus toxoids-acellular pertussis 5, hepatitis B, inactivated poliovirus vaccine and Haemophilus influenzae type b (DTaP5-HB-IPV-Hib) is a new investigational, fully liquid, combination vaccine containing a 5-antigen pertussis component and is designed to protect against 6 infectious diseases., Methods: In this multicenter, double-blind, comparator-controlled, phase III study (NCT01341639) conducted in Finland, Germany and Belgium, healthy infants were randomized 1:1 to receive 1 of 2 immunization regimens. The DTaP5-HB-IPV-Hib group received the investigational hexavalent vaccine (DTaP-HB-IPV-Hib) and the Control group received Infanrix-hexa (DTPa3-HBV-IPV/Hib) at 2, 3, 4 and 12 months of age. Both groups received concomitantly Prevnar 13 (PCV13) and Rotateq (RV5) at 2, 3 and 4 months of age and ProqQad (MMRV) at 12 months of age. MMRV was also administered to all study subjects at 13 months of age., Results: A total of 628 subjects in the DTaP5-HB-IPV-Hib group and 622 subjects in the Control group were randomized. In a per-protocol analysis, immune responses to vaccine antigens 1 month after dose 3 and after the toddler dose were noninferior in the DTaP5-HB-IPV-Hib group as compared with the Control group. The DTaP5-HB-IPV-Hib group responses to MMRV given concomitantly at 12 months were all noninferior compared with the Control group. Solicited adverse event rates after any dose, including fever, were similar in both groups. Most adverse events were mild-to-moderate and did not lead to subject withdrawal. Vaccine-related serious adverse events occurred infrequently in the DTaP5-HB-IPV-Hib group (0.3%) and the Control group (0.2%)., Conclusions: The safety and immunogenicity of DTaP5-HB-IPV-Hib is comparable to Control when administered in the 2-month, 3-month, 4-month and 12-month schedule. DTaP5-HB-IPV-Hib has the potential to provide a new hexavalent option for pediatric combination vaccines, aligned with recommended immunizations in Europe.

Background: The aim of the study was to compare efficacy, immunogenicity and safety of Hepavax-Gene TF (thimerosal-free) vaccine with comparator in Chinese neonates., Methods: A double-blind, randomized, parallel-group, stratified study was conducted at multiple sites in China in healthy neonates, consisting of 3 doses of Hepavax-Gene TF or Engerix-B vaccines administered at birth, 1 and 6 months of age, with a 6-month follow-up after vaccination. On the basis of hepatitis B virus (HBV) infection status of mothers, infants were assigned to one of 2 study strata for mothers positive for HBV infection (stratum 1), with or without active replicating virus (substrata 1a, 1b), and for HBV negative mothers (stratum 2)., Results: Mother-to-child HBV transmission was prevented in >95% of neonates immunized with Hepavax-Gene TF in stratum 1 at all timepoints and was noninferior to Engerix-B. Seroprotection rates (anti-HBs antibody ≥10 IU/L) at 1 and 6 months postvaccination for Hepavax-Gene TF were over 90% for all exposed neonates. Immunogenicity of Hepavax-Gene was noninferior to Engerix-B except for neonates in substratum 1a at 12 months. Geometric mean concentrations between vaccine groups were not significantly different for neonates at all timepoints except in substratum 1b at 7 months. Both vaccines were well tolerated and had similar local and systemic adverse event profiles., Conclusions: Hepavax-Gene TF vaccine was equally effective and noninferior to Engerix-B in terms of prevention of mother-to-child HBV transmission in neonates born to mothers positive for hepatitis B surface antigen. Both vaccines elicited seroprotective levels in >90% of all exposed neonates at 12-month follow-up. Both vaccines were well tolerated with similar adverse event profiles.

Background: Immune responses and safety profiles may be affected when vaccines are coadministered. We evaluated the immunogenicity, safety and reactogenicity of a booster dose of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D-conjugate (PHiD-CV; Synflorix GSK Vaccines) and DTPa-IPV-Hib (Pediacel Sanofi Pasteur MSD) when coadministered., Methods: We performed booster assessment in a randomized controlled trial in the Netherlands. Of 780 enrolled healthy infants, 774 toddlers participated in the booster phase and received (1:1:1) (1) PHiD-CV + DTPa-HBV-IPV/Hib (Infanrix hexa, GSK Vaccines), (2) PHiD-CV + DTPa-IPV-Hib, or (3) 7-valent pneumococcal conjugate vaccine (7vCRM, Prevenar/Prevnar, Pfizer, Inc.) + DTPa-IPV-Hib at 2, 3, 4 and 11-13 months old. Blood samples were taken postprimary, prebooster, 1 and 12 months postbooster., Results: Antipneumococcal antibody responses were comparable between both PHiD-CV groups, except for serotype 18C (conjugated to tetanus toxoid). Anti-18C antibody geometric mean concentrations (GMCs) were higher when coadministered with DTPa-HBV-IPV/Hib. For each vaccine serotype, the percentages of children with antibody concentration ≥ 0.20 μg/mL were within the same ranges between PHiD-CV groups (93.8%-100%). The same was observed for the percentages of participants with opsonophagocytic activity titer ≥ 8 (90.9%-100%). When comparing both DTPa-IPV-Hib groups, postbooster antidiphtheria antibody GMCs were higher when coadministered with 7vCRM, while antitetanus and antipolyribosyl-ribitol phosphate antibody GMCs were higher with PHiD-CV coadministration. Regardless, antibody levels to these antigens were well above thresholds. Safety and reactogenicity profiles were comparable between groups., Conclusions: Coadministration of a booster dose of PHiD-CV and DTPa-IPV-Hib was immunogenic and well tolerated.

Background: Not many data are available on long-term immunity against hepatitis B (HB) for children vaccinated under real-life conditions., Methods: Two hundred and thirty-two children and adolescents vaccinated 6-14 years earlier in pediatric practices were examined for conditions of vaccination and markers of protection as anti-HBs, anamnestic response to a booster dose and cell-mediated immunity., Results: Fifty-six percent of the participants were vaccinated according to the German vaccination recommendations (group 1). In 44.0% (group 2), these recommendations were not followed. Anti-HBs concentrations of ≥10 IU/L were found in 53.1% of group 1 and 45.1% of group 2 participants. A booster dose resulted in 91 of 99 participants in having an anamnestic response, in 3 (5.9%) of group 1 and 5 (10.4%) of group 2 anti-HBs remained below 10 IU/L. In group 1, postbooster anti-HBs concentration was inversely correlated with time since the last vaccination. Cellular immune responses were seen in only 5% of revaccinated individuals before the booster, increasing to 30% thereafter., Conclusions: Under real-life conditions about half of vaccinees have lost protecting antibodies 6-14 years after vaccination in infancy, but in approximately 90% of them, immune memory was demonstrated. However, as memory may wane, revaccination at a time when boostability is still present might be considered.

Background: To evaluate the safety and immunogenicity of the thiomersal-free (TF) and thiomersal-containing (TC) formulations of Hepavax-Gene in healthy Vietnamese neonates., Methods: A single-blind, randomized, controlled study in Ho Chi Minh City, Vietnam. Healthy infants, born after a normal gestational period (37-42 weeks) to hepatitis B surface antigen-negative mothers, participated in the study. Subjects were randomly allocated in a 1:1 ratio to receive either Hepavax-Gene TC or Hepavax-Gene TF using a standard 0-1-6-month administration schedule. Postvaccination blood samples were taken at months 1, 6 and 7. Parents/legal guardians recorded solicited local and systemic adverse events up to 4 weeks after each vaccination., Results: Very high proportions of subjects were seroprotected. Seroprotection rates at 1, 6 and 7 months were all above 95% using a 10 IU/L cutoff, and were mostly above 90% using a 100 IU/L cutoff. Seroprotection rates between the 2 formulations were equivalent within a 5% margin for either cutoff titer both after 6 and 7 months. There were no significant differences in the number of adverse events reported between the 2 formulations. Safety results were in line with previous reports for Hepavax-Gene. Both formulations of Hepavax-Gene were well tolerated. There were no local adverse events reported in the TF group. No serious adverse events were reported during the study., Conclusions: The thiomersal-free formulation of Hepavax-Gene was noninferior to the thiomersal-containing formulation of Hepavax-Gene in terms of immunogenicity. There was evidence that the thiomersal-free vaccine was associated with fewer local adverse events.

Background: The immunogenicity and safety of the investigational diphtheria, tetanus, acellular pertussis, hepatitis B, poliomyelitis, Haemophilus influenzae type b (Hib) and meningococcal serogroup C (MenC) heptavalent combination vaccine were compared with those of licensed control vaccines., Methods: In this open, phase II, randomized study (NCT01090453), 480 infants from Germany, France and Canada received the heptavalent vaccine (Hepta group) or hexavalent and monovalent MenC control vaccines (HexaMenC group) co-administered with a 13-valent pneumococcal conjugate vaccine at 2, 4 and 12 months of age. Immunogenicity was measured 1 month after the second primary dose, and before and 1 month after the booster dose. Safety and reactogenicity were also evaluated., Results: Non-inferiority of immune responses to MenC and Hib induced by 2-dose primary vaccination with the heptavalent vaccine versus control vaccines was demonstrated. In exploratory analyses, postprimary and postbooster functional antibody geometric mean titers against MenC tended to be lower (1119.5 vs. 3200.5; 2653.8 vs. 6028.4) and antibody geometric mean concentrations against Hib higher (1.594 vs. 0.671 μg/mL; 17.678 vs. 13.737 μg/mL) in the Hepta versus the HexaMenC group. The heptavalent and control vaccines were immunogenic to all other antigens, although immune responses to poliovirus were lower than expected in both groups. No differences in safety and reactogenicity profiles were detected between groups., Conclusions: The heptavalent vaccine induced non-inferior MenC and Hib responses compared with control vaccines. Both vaccination regimens, when administered at 2, 4 and 12 months of age, had comparable safety profiles and were immunogenic to all antigens, with lower-than-expected responses to poliomyelitis.

Background: Combination diphtheria-tetanus-5 component acellular pertussis-inactivated poliovirus-Haemophilus influenzae b conjugate-hepatitis B vaccine (DTaP5-IPV-Hib-HepB) administered either concurrently with 7-valent pneumococcal conjugate vaccine (PCV7) or 1 month apart was generally safe and immunogenic at 2, 4 and 6 months of age. This study examined the effects of a booster dose at age 15 months., Methods: Participants were randomized to DTaP5-IPV-Hib-HepB plus PCV7, DTaP5-IPV-Hib-HepB with PCV7 administered 1 month later or a pentavalent DTaP5-IPV/Hib plus HepB plus PCV7 at 15 months of age in a randomized, open-label, phase IIb clinical trial. Immunogenicity endpoints were rates of seroresponse to pertussis toxoid, filamentous hemagglutinin, pertactin and fimbriae types 2 and 3; rates of seroprotection against (Hib) polyribosylribitol phosphate capsular polysaccharide, hepatitis B surface antigen, diphtheria toxoid, tetanus toxoid and poliovirus types 1, 2 and 3; and geometric mean titers to all vaccine antigens. Safety endpoints included solicited injection-site reactions and systemic and serious adverse events., Results: Seroresponse/seroprotection rates for all antigens exceeded prespecified criteria in both groups that received the hexavalent DTaP5-IPV-Hib-HepB; in the group that received the currently licensed pentavalent vaccine, seroresponse/seroprotection rates exceeded the criteria for all antigens except filamentous hemagglutinin. Seroresponse rates were ≥88.9% for pertussis antigens and seroprotection rates against polyribosylribitol phosphate capsular polysaccharide, hepatitis B surface antigen, diphtheria toxoid, tetanus toxoid and poliovirus antigens were ≥95.1% in recipients of DTaP5-IPV-Hib-HepB., Conclusions: DTaP5-IPV-Hib-HepB administered concomitantly with PCV7 or 1 month apart at 15 months of age following the infant series was well-tolerated and elicited antibody responses to all vaccine antigens, with no significant interference from concomitant PCV7 administration (clinicaltrials.gov registration number NCT00362427).

Background: More than 2 billion people worldwide have been exposed to hepatitis B virus (HBV). To prevent these infections, Senegal and Cameroon integrated the HBV vaccine into their Expanded Program on Immunization (EPI) in 2005, as did the Central African Republic (CAR) in 2008. We evaluated the prevalence of HBV exposure and infection after the integration of the HBV vaccine in the EPI., Methods: An observational cross-sectional study was conducted among the hospitalized children 3 months to 6 years of age in Cameroon, CAR and Senegal. Plasma was collected for the detection of anti-HBc, anti-HBs and hepatitis B surface antigen in children with anti-HBc and anti-HBs., Results: Between April 2009 and May 2010, 1783 children were enrolled, 19.4% of whom were anti-HBc positive. The percentage of children with anti-HBc was 44.4% among the children younger than 6 months, decreasing after 6 months to reach 18.8% at 12 months. This decline was followed by a rapid increase in anti-HBc positivity rate in CAR observed as early as 12 months of age compared with Cameroon and Senegal, where the anti-HBc increased between 18 and 36 months of age, respectively. The prevalence of hepatitis B surface antigen-positive children was significantly higher in CAR than that in Cameroon and Senegal (5.1% versus 0.7% and 0.2%; P < 0.001). Socioeconomic level, age and country were factors associated with the presence of anti-HBc., Conclusions: Passive transfer of anti-HBc maternal antibodies versus HBV exposure could be differentiated as early as 12 months of age. The low prevalence of anti-HBc and hepatitis B surface antigen among children born after the integration of HBV vaccine in the EPI in Cameroon and Senegal suggests a positive impact of HBV vaccination.

Objective: To assess antibody persistence and booster immunogenicity and safety of a new, fully liquid, hexavalent DTaP-IPV-Hep B-PRP-T vaccine., Methods: Phase III, open-label, 2-center trial. Infants previously primed at 6, 10, 14 weeks of age with DTaP-IPV-Hep B-PRP-T either without (group 1: N = 218) or with hepatitis B at birth (group 3: N = 130) or control DTwP-Hib, hepatitis B and oral poliovirus vaccine vaccines (group 2: N = 219) received the same vaccine(s) as booster (except hepatitis B for group 2) at 15-18 months of age, coadministered with measles/mumps/rubella and varicella vaccines (MMR+V). All participants had received measles vaccine at 9 months of age. Antibodies were measured prebooster and 1 month postbooster vaccination. Safety was evaluated from parental reports. Analyses were descriptive., Results: Antibody persistence (seroprotection and concentration) at 15-18 months of age was high for each valence and similar in each group, except for Hep B (highest in group 3 [extra dose of hepatitis B]) and PRP (highest in group 2). Postbooster seroprotection (D, T, IPV, Hep B, PRP) and seroconversion (pertussis toxin and filamentous hemagglutinin) rates were high and similar in each group (excluding Hep B in group 2 [no booster]); geometric mean antibody levels increased markedly in all groups. The response to MMR+V was similar in each group. All vaccines were well tolerated., Conclusions: A booster dose of the new DTaP-IPV-Hep B-PRP-T vaccine at 15-18 months of age is highly immunogenic and safe compared with licensed comparators, following primary series administration in the Expanded Program on Immunization schedule, with or without a hepatitis B vaccine at birth and coadministered with MMR+V.

Background: Combination vaccines offer protection against multiple diseases with fewer injections. This study evaluated the immunogenicity and safety of an investigational diphtheria, tetanus, acellular pertussis, hepatitis B, poliomyelitis, Haemophilus influenzae type b (Hib) and meningococcal serogroup C (MenC) heptavalent combination vaccine (heptavalent vaccine) given as 4 doses at 2, 3, 4 and 12-18 months of age., Methods: In this randomized, open, phase II study (NCT00970307/NCT01171989) conducted in Poland, 421 infants were enrolled to receive the heptavalent vaccine or licensed comparator vaccines. Immunogenicity against study vaccine antigens was measured prior to and 1 month after primary and booster vaccinations. Safety and reactogenicity of the vaccines were also evaluated., Results: The primary noninferiority objectives of the MenC and Hib immune responses induced by the heptavalent vaccine versus comparator vaccines were reached after primary vaccination, but no statistical conclusion could be drawn after booster dose. One month after primary and booster vaccinations, ≥98.4% of the heptavalent vaccine recipients were seroprotected for MenC and Hib. Exploratory analyses indicated that the heptavalent vaccine induced higher postprimary vaccination antibody geometric mean concentrations against Hib, but lower postprimary and postbooster vaccinations geometric mean titers against MenC compared with the relevant comparator vaccines. The reactogenicity profiles of the vaccines were acceptable, although 1 infant vaccinated with the heptavalent vaccine experienced a serious adverse event (thrombocytopenia) considered possibly related to vaccination., Conclusions: The heptavalent vaccine was immunogenic and had a clinically acceptable safety profile when administered to infants and toddlers.

Background: The duration of protection after hepatitis B vaccination in early infancy is unclear and may be related to vaccination schedule, dosage, vaccine type and population characteristics. Factors potentially influencing waning immunity were assessed., Methods: A systematic review was performed. The main outcomes were prevalence of anti-hepatits B antibodies ≥ 10 mIU/mL after primary or booster vaccination. Factors potentially influencing protection were assessed in an adjusted random-effects meta-analysis model by age for both outcomes. Results of both meta-analyses were combined in a prognostic model., Results: Forty-six studies reporting on the anti-hepatits B antibodies ≥ 10 mIU/mL 5 to 20 years after primary immunization and 29 on booster response were identified. The adjusted meta-analyses identified maternal carrier status (odds ratio [OR]: 2.37 [1.11; 5.08]), lower vaccine dosage than presently recommended (OR: 0.14 [0.06; 0.30]) and gap time between last and preceding dose of the primary vaccine series (OR: 0.44 [0.22; 0.86]) as determinants for persistence of anti-hepatits B antibodies ≥ 10. A lower vaccine dosage was also associated with failure to respond to booster (OR: 0.20 [0.10; 0.38]). The prognostic model predicted long-term protection of 90% [77%; 100%] at the age of 17 years for offspring of noncarrier mothers vaccinated with a presently recommended dose and vaccination schedule., Conclusions: Based on meta-analyses, predictors of waning immunity after hepatitis B vaccination in infancy could be identified. A prognostic model for long-term protection after hepatitis B vaccination in infancy was developed.

Background: A 13-valent pneumococcal conjugate vaccine (PCV13) has been licensed in >100 countries to broaden coverage against pneumococcal disease. We assessed whether PCV13 interferes with immune responses to concomitantly administered routine pediatric vaccines., Methods: Healthy US infants were randomly assigned in 2 studies to receive PCV13 or 7-valent PCV (PCV7) at age 2, 4 and 6 months concomitantly with diphtheria, tetanus, acellular pertussis, inactivated polio virus, hepatitis B and Haemophilus influenzae type b, and at age 12-15 months with measles, mumps, rubella, varicella and hepatitus A. Antibodies to pertussis antigens, diphtheria, tetanus toxoid, poliovirus types 1-3, Haemophilus influenzae type b polyribosylribitol phosphate capsular polysaccharide and polyribosylribitol phosphate capsular polysaccharide were measured 1 month after the infant series; measles, mumps, rubella, varicella and polyribosylribitol phosphate capsular polysaccharide were determined 1 month after the toddler dose. Both the percentages of responders (subjects reaching a prespecified antibody concentration) and immunoglobulin G antibody geometric mean concentrations/titers were calculated for each concomitant vaccine antigen., Results: Not all assays were performed on all subjects. Data were available from 153 to 239 infants and 163-230 toddlers in the PCV13 group and 173-240 infants and 167-214 toddlers in the PCV7 group. One month after both infant series and the toddler dose, noninferiority criteria were met for all antigens with respect to percentage of responders in both PCV7 and PCV13 groups. Immunoglobulin G antibody geometric mean concentration/titer ratios (PCV13/PCV7) were 0.91-1.33 and 0.83-1.03 at 1 month after the infant series and toddler dose, respectively, and met predetermined noninferiority criteria., Conclusions: Immune responses to routine pediatric vaccines concomitantly administered with PCV13 were noninferior to responses achieved when administered with PCV7.

Objective: The aim of this study was to determine the prevalence of hepatitis B virus (HBV) infection in a cohort of HIV-infected Rwandan children and adolescents on combination antiretroviral therapy (cART), and the success rate of HBV vaccination in those children found to be HBV negative., Methods: HIV-infected children and adolescents (age 8-17 years) receiving cART with CD4 T-cells count ≥200 cells/mm and/or ≥15% and without prior HBV vaccination (by history, vaccination cards and clinic records) underwent serologic testing for past (negative HBV surface antigen [HBsAg] with positive antibody to HBV core antigen [cAb] and to HBsAg [anti-HBs]) or active HBV infection (positive HBsAg). Children with any positive HBV serologic tests were excluded from further vaccination; all others completed 3 HBV immunizations with 10 µg of ENGERIX-B. Anti-HBs titer was measured 4-6 weeks after the last immunization., Results: Of 88 children, 6 (7%) children had active HBV infection and 8 (9%) had past HBV infection. The median (interquartile range) age, CD4 T-cell count and cART duration were 12.3 (10.1-13.9) years, 626 (503 to 942) cells/mm and 1.9 (1.5-2.7) years, respectively. Seventeen children had detectable plasma HIV-1 RNA. Seventy-3 children completed 3 immunizations with median (interquartile range) postimmunization anti-HBs concentration of 151 mIU/mL (1.03-650). Overall, 52 children (71%, 95% confidence interval: 61-82) developed a protective anti-HBs response. HIV-1 RNA and CD4 T-cell count were independent predictors of a protective anti-HBs response. Protective anti-HBs response was achieved in 82% of children with undetectable HIV-1 RNA and 77% with CD4 T cells ≥350/mm., Conclusions: The substantial HBV prevalence in this cohort suggests that HIV-infected Rwandan children should be screened for HBV before cART initiation. HIV viral suppression and CD4 T cells ≥350/mm favored the likelihood of a protective response after HBV vaccination.

Background: Bulgaria adopted the World Health Organization recommendation of routine universal infant vaccination against hepatitis B in 1991. Nevertheless, only a few studies evaluated the protection after the vaccination against hepatitis B, especially in children. The objective of this study was to investigate the duration of protection against hepatitis B in children aged 5-15 years after primary immunization, by measuring the immune and anamnestic immune response and possible breakthrough infections., Methods: A total of 141 children (aged 5-17 years) were recruited randomly and divided into 3 groups, approximately 5 years (group 1), 10 years (group 2) and 15 years (group 3) after primary immunization with a recombinant hepatitis B vaccine; they were tested for hepatitis B markers: hepatitis B surface antigen anti-hepatitis core antibody and antibodies to hepatitis B surface antigen (anti-HB). A booster dose of vaccine was administered to 23 children with titers of anti-HBs antibodies below the threshold considered to be protective (<10 mIU/mL). Anti-HBs concentrations and geometric mean concentration (GMC) were determined before and 21-28 days after the booster vaccination., Results: Protective anti-HBs antibodies were detected in 95 of 141 (67.4 %) tested children, with a GMC of 63.57 mIU/mL. The seroprotection rate and GMC by groups was respectively: 84.6% and GMC of 76.05 mIU/mL in group 1; 55.8% and GMC of 58.1 mIU/mL in group 2; and 61.1% and GMC of 50.33 mIU/mL in group 3. Hepatitis B surface antigen and anti-hepatitis core antibody were found in 1 of the 141 subjects (0.7%). Of the remaining 140 children, 95 had anti-HBs ≥10 mIU/mL, and anti-hepatitis core antibodies were not detected. A booster dose of hepatitis B vaccine was administered to 23 of 45 (51%) children with anti-HBs <10 mIU/mL. Anamnestic immune response was shown in 100% of the children: the GMC was 337.38 mIU/mL and protective antibodies ranged between 15 and 955 mIU/mL., Conclusion: The study demonstrates the presence of immune memory and protection 5-15 years after the initial course of newborn immunization with recombinant vaccines against hepatitis B.

Background: DTaP₅-IPV-Hib-HepB, an investigational hexavalent combination vaccine, was evaluated for safety and immunogenicity, when administered to infants with heptavalent pneumococcal conjugate vaccine (PCV7)., Methods: Infants were randomized to receive DTaP₅-IPV-Hib-HepB plus PCV7, DTaP₅-IPV-Hib-HepB with PCV7 administered 1 month later or DTaP₅-IPV/Hib plus HepB plus PCV7 at 2, 4 and 6 months of age in an open-label, phase IIb trial. Vaccine responses were assessed by pertussis toxoid, filamentous hemagglutinin, pertactin and fimbriae types 2/3 seroconversion rates, Haemophilus influenzae type b polyribosylribitol phosphate capsular polysaccharide, hepatitis B surface antigen, diphtheria toxoid, tetanus toxoid and poliovirus types 1, 2 and 3 seroprotection rates and geometric mean titers. Solicited injection site and systemic reactions, serious adverse events, and other safety outcomes were reported., Results: Seroprotection rates to polyribosylribitol phosphate, hepatitis B surface antigen, diphtheria toxoid, tetanus toxoid and poliovirus antigens across all groups met or exceeded predetermined acceptability criteria. Seroconversion rates to pertussis toxoid, pertactin and fimbriae types 2/3, but not filamentous hemagglutinin, met such criteria. Antidiphtheria antibodies were significantly lower when PCV7 was coadministered. Geometric mean titers to the other antigens of the hexavalent and PCV7 vaccines were all high and similar in the 2 groups. No safety signals were noted., Conclusions: DTaP₅-IPV-Hib-HepB administered at 2, 4 and 6 months of age concomitantly with PCV7 was well tolerated and elicited robust antibody responses to all but the antidiphtheria antigens for which there may be evidence of immune interference. Only filamentous hemagglutinin did not meet seroconversion rate acceptability criteria.

Objective: This trial assessed the safety of a fully liquid investigational hexavalent DTaP-IPV-Hep B-PRP-T vaccine containing 10 μg Hansenula polymorpha-derived recombinant hepatitis B (hep B) antigen for primary vaccination of infants at 2, 4 and 6 months of age compared with licensed comparators., Methods: Participants received the DTaP-IPV-Hep B-PRP-T vaccine (group 1, N = 1422) or licensed DTwP-Hep B//Hib (Tritanrix-Hep B/Hib) and oral poliovirus vaccines (group 2, N = 711). The incidence of severe fever (≥ 39.6°C rectal equivalent) in the 2 groups was compared statistically; reactogenicity was evaluated from parental reports. Anti-Hep B antibody titers were measured in a subset of participants (no hepatitis B vaccination at birth) 1 month after dose 3., Results: The investigational vaccine was well tolerated. After any dose, fever (rectal equivalent temperature ≥ 38°C) was observed in 74.8% and 92.7% of participants in groups 1 and 2; severe fever was observed in 4.0% and 5.5% of participants. Solicited injection site and systemic reactions were numerically less frequent in group 1 than group 2, although this difference was not assessed statistically. In both groups, all participants included in the immunogenicity analysis achieved anti-Hep B ≥ 10 mIU/mL and ≥ 96.2% of participants achieved anti-Hep B ≥ 100 mIU/mL, although geometric mean titer was approximately 3-fold lower for the investigational vaccine., Conclusion: This new, fully liquid acellular pertussis hexavalent vaccine demonstrated less reactogenicity than the licensed comparator whole cell pertussis vaccine and was highly immunogenic for the new Hep B valence.

Objective: To assess antibody persistence after vaccination with a new, fully liquid, hexavalent DTaP-IPV-Hep B-PRP-T vaccine at 18 months of age versus licensed DTaP-IPV//PRP-T and hepatitis B (Hep B) vaccines, and to assess the immunogenicity and safety of a subsequent DTaP-IPV//PRP-T booster., Methods: A phase III, open-label, single-center study was conducted. Infants previously primed with 3 doses of DTaP-IPV-Hep B-PRP-T (Hexaxim: N = 232 [group 1]) or DTaP-IPV//PRP-T and hepatitis B vaccine (Pentaxim + Engerix B Pediatrico: N = 226 [group 2]) at 2, 4, and 6 months of age received a DTaP-IPV//PRP-T booster at 18 months of age. Antibodies were measured before and 1 month after booster vaccination. Safety was evaluated from parental reports. Analyses were descriptive., Results: Antibody persistence was high and similar in each group for each antigen except for Hep B, for which the percentage (95% confidence interval) of participants with a titer of ≥ 10 mIU/mL was higher in group 2 (99.5% [97.5%, 100.0%]) than in group 1 (85.5% [80.3%, 89.8%]). Postbooster seroprotection (diphtheria, tetanus, inactivated poliovirus, polyribosyl-ribitol phosphate) and serconversion (pertussis toxoid, filamentous hemagglutinin) rates were high and similar in each group, and geometric mean antibody concentrations increased markedly in both groups. Safety after the booster vaccination was good and independent of the primary-series vaccine, although one serious adverse event of convulsions was considered to be vaccine related., Conclusions: The DTaP-IPV/PRP-T booster vaccination at 18 months of age was similarly immunogenic and well tolerated after primary-series vaccination with either the investigational hexavalent vaccine or the reference pentavalent vaccine. This confirms the suitability of a booster vaccination of DTaP-IPV//PRP-T after a primary series of the new DTaP-IPV-Hep B-PRP-T vaccine.

Background: Induction of immunologic memory was assessed following primary vaccination with 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV)., Methods: Infants were randomized (1:1) to receive 3 doses of PHiD-CV or 7vCRM (7-valent CRM197-conjugated pneumococcal conjugate vaccine [PCV]) at 2, 3, and 4 months of age followed by 23-valent pneumococcal polysaccharide vaccine (23vPS) booster dose at 11 to 14 months of age. Pneumococcal geometric mean antibody concentrations (GMCs) and opsonophagocytic activity (OPA) geometric mean titers were measured., Results: Postprimary immune responses were consistent with those in previous PHiD-CV and 7vCRM studies. Following 23vPS boosting, vaccine serotype-specific antibody GMCs increased 6.5- to 33.3-fold and 4.8- to 32.2-fold versus prebooster in the PHiD-CV and 7vCRM groups, respectively. Postbooster OPA titers increased 2.8- to 38.8-fold and 2.6- to 58.9-fold, respectively. Postbooster antibody GMCs exceeded postprimary levels but, for some serotypes, postbooster OPA geometric mean titers were lower than postprimary in both groups. An additional dose of the same PCV received for priming was administered to 52 children aged 46 to 50 months, resulting in higher responses versus postprimary vaccination for all serotypes, but not always higher than post-23vPS booster., Conclusions: Induction of immunologic memory following PHiD-CV priming was confirmed. Additional PCV boosting in 4-year-olds did not provide strong evidence of hyporesponsiveness induced by previous 23vPS boosting. However, our results did not rule out depletion of the memory B cell pool following 23vPS vaccination, resulting in subsequent attenuated immune responses, and therefore support the use of PCV rather than 23vPS for booster vaccination in the second year of life.

Long-term persistence of antibodies against hepatitis A and B (anti-HAV and anti-HBs) were evaluated in 1- to 11-year-old children following 2 doses (0, 6 months) of hepatitis A and B vaccine. Ten years postvaccination, all subjects were anti-HAV seropositive (≥15 mIU/mL), 81.7% had anti-HBs antibody concentrations ≥10 mIU/mL. All subjects with anti-HBs concentrations <10 mIU/mL, mounted a vigorous anamnestic response to an HBV vaccine challenge dose indicating the presence of immunologic memory against hepatitis B.

Background: A modified process hepatitis B vaccine (mpHBV) uses higher phosphate content in the manufacturing process relative to the current product, Recombivax-HB. The higher phosphate is thought to improve antigen presentation, and thereby, increase antibody production. The mpHBV was previously shown to be well tolerated and immunogenic in adults. The current study tested a 2-, 4-, 6-month vaccination schedule and a higher dose formulation (10 μg mpHBV) in healthy infants., Methods: In a randomized, double-blind study, healthy infants (N = 1718), approximately 2 months of age, received a 0.5-mL intramuscular dose of 5-μg mpHBV, Recombivax-HB (5 μg), 10-μg mpHBV, or Engerix-B (10 μg) at day 1, month 2, and month 4 (2, 4, 6 months of age). Serum antibody to hepatitis B surface antigen (anti-HBs) was analyzed at month 7. The geometric mean titer (GMT) and seroprotection rate (SPR; % subjects with anti-HBs titer ≥ 10 mIU/mL) were determined 1 month after the third dose., Results: Month 7 SPRs were 99.3% (402/405, 95% confidence interval [CI]: 98.3, 100) in the 5 μg mpHBV group, 100.0% (398/398, 95% CI: 99.9, 100) in the 10 μg mpHBV group, 98.5% (400/406, 95% CI: 97.2, 99.8) in the Recombivax-HB group, and 99.5% (398/400, 95% CI: 98.7, 100) in the Engerix-B group. Month 7 GMTs (mIU/mL) were 748.2 (95% CI: 672.0, 833.1) in the 5 μg mpHBV group, 981.5 (95% CI: 891.0, 1081.2) in the 10 μg mpHBV group, 376.8 (95% CI: 331.4, 428.5) in the Recombivax-HB group, and 556.6 (95% CI: 491.8, 629.9) in the Engerix-B group. The percentages of subjects reporting injection-site or systemic adverse events were similar across the vaccination groups., Conclusions: All 4 hepatitis B vaccines elicited high anti-HBs SPRs. After dose 3, anti-HBs GMT were highest in the 10 μg mpHBV group, but did not meet the predefined criteria for superiority. All vaccines were well tolerated.

Background and Aims: Assessment of a new, fully liquid, investigational hexavalent DTaP-IPV-Hep B-PRP-T vaccine (Hexaxim, Sanofi Pasteur), containing the same active ingredients as Pentaxim (DTaP-IPV//PRT-T) and 10 μg Hansenula polymorpha-derived recombinant hepatitis B (Hep B) surface antigen, Sanofi Pasteur, in Argentinean infants., Methods: Infants born to Hep B surface antigen seronegative mothers were randomized to receive the DTaP-IPV-Hep B-PRP-T vaccine or Pentaxim and Engerix B Pediatrico (Hep B monovalent) vaccines at 2, 4, 6 months of age. Antibody titers were measured before and 1 month after 3-month primary vaccination. Noninferiority analyses were performed on seroprotection/seroconversion rates. Safety was evaluated descriptively up to 1 month after primary vaccination., Results: A total of 624 participants were enrolled, 312 participants were randomized to each group, and 604 participants completed the trial. The DTaP-IPV-Hep B-PRP-T vaccine was demonstrated as noninferior to the Pentaxim and Hep B monovalent vaccines with seroprotection/seroconversion rates 1 month postdose 3 for each valence. The anti-Hep B geometric mean titer 1-month postdose 3 for the investigational DTaP-IPV-Hep B-PRP-T primary series was similar to the monovalent Hep B control. The overall incidence of adverse events was similar among the 2 groups., Conclusions: The new, fully liquid, investigational DTaP-IPV-Hep B-PRP-T vaccine (Hexaxim) is highly immunogenic and safe when compared with licensed comparators, warranting further development.

Background: Assessment of primary vaccination of a new fully liquid, hexavalent investigational DTaP-IPV-Hep B-PRP-T vaccine (Hexaxim) in South African infants., Methods: Infants were randomized to the following at 6, 10, and 14 weeks of age (Expanded Program on Immunization schedule): DTaP-IPV-Hep B-PRP-T (Group 1; N = 286); DTwP-Hib, hepatitis B, and OPV vaccines (Group 2; N = 286); or DTaP-IPV-Hep B-PRP-T vaccine with hepatitis B vaccine at birth (Group 3; N = 143). Antibody titers were measured before vaccination (pertussis toxoid, filamentous hemagglutinin) and postprimary vaccination (all valences). Noninferiority analyses were performed for Group 1 versus Group 2 for seroprotection rates. Safety was evaluated from parental reports., Results: Noninferiority (Group 1 minus Group 2) was demonstrated for anti-HBs, -PRP, -diphtheria, -tetanus, and -polio 1, 2, 3 (lower 95% confidence interval for the difference was -8.20 to 3.46). Anti-HBs antibody titers ≥10 mIU/mL and anti-PRP ≥0.15 μg/mL were ≥95.4% in each group. Seroprotection rates were also high for the other antigens. Seroconversion rates (4-fold increase from pre- to postvaccination) were 93.6%, 83.2%, and 95.1% in Groups 1, 2, and 3, respectively, for anti-pertussis toxoid and 93.1%, 57.7%, and 90.0% for anti-filamentous hemagglutinin. Anti-HBs GMTs were 330, 148, and 1913 mIU/mL for Groups 1, 2, and 3, respectively. Reactogenicity was similar in each group. Fever ≥39.0°C occurred in 1.7%, 0.4%, and 0.0% of infants in Groups 1, 2, and 3, respectively; no extensive limb swelling, hypotonic-hyporesponsive episodes, or vaccine-related serious adverse events were reported., Conclusions: The new, fully liquid, investigational hexavalent vaccine in the Expanded Program on Immunization schedule, with/without hepatitis B at birth, is highly immunogenic and safe compared with control vaccines, warranting further development.

This open-label, randomized study challenged 4- to 8-year-old children from Spain (N = 1478) with a single dose of hepatitis B vaccine to estimate anamnestic responses. At the time of preimmunization, 15.9% to 51.2% of subjects had antibody values ≥10 mIU/mL. One month postimmunization, 91.6% to 97.3% of subjects had antibody titers ≥10 mIU/mL. There were no serious, vaccine-related, adverse experiences, and no discontinuations as a result of adverse experience.

Background: Multiple studies have shown excellent response rates after hepatitis B immunization in youth; however, one previous study conducted in urban youth demonstrated poor responses., Methods: Urban youth, ages 12 to 17 years, at participating Adolescent Medicine Trials Network for HIV/AIDS Interventions Clinical/Research sites were randomized to receive either 2 doses of Recombivax HB (10 microg hepatitis B surface antigen) or Twinrix (20 microg hepatitis B surface antigen and 720 EL.U hepatitis A antigen) at 0 and 24 weeks. Safety data were collected and antibody measures performed at 0, 28, and 76 weeks., Results: A total of 123 subjects were enrolled and 102 had week 28 serum samples available for antibody measure. A positive response (serum antibody > or =10 mIU/mL) to hepatitis B antigen was documented in 41 of 47 (87.2%; 95% confidence interval [CI] 74.3%-95.2%) Recombivax HB recipients and in 52 of 55 (94.6%; 95% CI, 84.9%-98.9%) Twinrix recipients (P = 0.295). In an adjusted analysis, those identified as Hispanic ethnicity (N = 86) were more likely to have a positive response (odds ratio 7.38, 95% CI, 1.56-34.95; P = 0.0018); whereas those who identified as not heterosexual (N = 9) were less likely to respond (odds ratio = 0.12, 95% CI, 0.02-0.74). The majority of youth in the Twinrix arm were hepatitis A antibody positive at baseline (26/51; 51%); however, 24 of 25 hepatitis A antibody negative youth responded to the hepatitis A component. Both vaccines were safe., Conclusions: Response rate to 2 doses of Recombivax HB in urban youth is lower than previous studies suggest. The factors associated with diminished response are not known.

Background: Infants less than 3 months of age are at highest risk of hospitalization and death from pertussis. Several studies have examined antibody responses to pertussis vaccines at birth but no previous study has evaluated 2 doses of monovalent acellular pertussis vaccine (aPV) before 2 months of age., Methods: Seventy-six newborns were randomized at birth to 3 groups-aPV at birth and 1 month, aPV at birth, and control. All infants received hepatitis B vaccine (HBV) at birth followed at 2, 4, and 6 months by a combination vaccine including aPV, diphtheria, tetanus, Haemophilus influenzae type b (Hib), hepatitis B, polio antigens and 7 valent conjugate pneumococcal vaccine. IgG antibody responses to pertussis toxoid (PT), filamentous hemagglutinin (FHA), and pertactin (PRN) were measured in maternal serum and in infants at 2, 4, 6, and 8 months of age. Antibody responses to hepatitis B, diphtheria, tetanus, and Hib were measured at 8 months only. A parental diary and active telephone follow-up occurred for 7 days after each vaccination., Results: The aPV birth dose was well tolerated. By 2 months of age, 22 of 25 (88%) of 2 dose recipients had detectable IgG antibody to PT (IgG PT) compared with 9 of 21 (43%) who received a birth dose only and 3 of 20 (15%) of controls. Infants in the 2 dose group had a geometric mean concentration (GMC) of IgG PT of 16 ELISA units per mL (EU/mL), 95% CI: 11 to 25, significantly higher than birth dose only (5 EU/mL, 95% CI: 3-8) and controls (3 EU/mL, 95% CI: 2-5). At 8 months of age, following 5, 4, and 3 doses of aP-containing vaccine, respectively, IgG PT had plateaued but IgG to FHA and PRN increased with successive doses. There was a trend to lower antibody responses for hepatitis B and Hib with higher numbers of Pa doses., Conclusion: These data suggest that aPV at birth and 1 month induces significantly higher IgG antibody against pertussis antigens by 2 months of age without reducing subsequent pertussis antibody responses. Larger and more detailed studies of aPV from birth are needed to evaluate other antibody responses and the potential of this approach to reduce death and morbidity from Bordetella pertussis infection in the first 3 months of life.

Background: To evaluate the impact of routine hepatitis B (HB) vaccination on the prevalence of chronic hepatitis B virus (HBV) infection among children in Pacific Island countries where HBV infection was highly endemic, we conducted HB serosurveys during 2000 to 2007 among women of childbearing age born before implementation of HB vaccination and among children born after its implementation., Methods: Serum specimens were collected from children aged 2 to 6 years and their mothers in Chuuk, Federated States of Micronesia in 2000, children aged 2 to 9 years and their mothers in Pohnpei, Federated States of Micronesia in 2005, and 5- to 9-year-old children and prenatal clinic patients in 2007 in Republic of the Marshall Islands (RMI). Specimens were tested for HB surface antigen (HBsAg) and antibodies to HB core antigen (total anti-HBc). HB vaccination coverage was determined from health department vaccination registries. We defined chronic HBV infection as the presence of HBsAg., Results: Birthdose and 3 dose HB vaccination coverage was 48% and 87%, respectively, in Chuuk, 87% and 90% in Pohnpei, and 49% and 93% in RMI. Chronic HBV infection prevalence among children was 2.5% (9/362) in Chuuk, 1.5% (7/478) in Pohnpei and 1.8% (6/331) in RMI. Chronic HBV infection prevalence among women was 9.2% (21/229) in Chuuk, 4.4% (10/229) in Pohnpei, and 9.5% (11/116) in RMI., Conclusions: Hepatitis B vaccination has resulted in a substantial decline in chronic infection in children in the Pacific Islands. HB vaccine effectiveness is high in this region, despite challenges in providing HB vaccine at birth and completing vaccination series on schedule.

Background: Study assessed the immunogenicity and safety of an investigational Haemophilus influenzae type b-Neisseria meningitidis serogroups C and Y-tetanus toxoid conjugate vaccine (HibMenCY-TT) in infants., Methods: In a single-blinded, controlled study, 609 infants were randomized 1:1 to receive primary vaccination (2, 4, and 6 months) with either HibMenCY-TT or monovalent Haemophilus influenzae type b tetanus toxoid conjugate vaccine (Hib-TT), co-administered with combined diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus vaccine and 7-valent pneumococcal conjugate vaccine. A second control group of 3- to 5-year-old children received a single dose of licensed meningococcal ACWY polysaccharide vaccine (MPSV4). Immunogenicity was measured before and 1 month after dose 3/MPSV4 using human (hSBA) and rabbit complement bactericidal assays (rSBA) and enzyme-linked immunosorbent assay assays for IgG antibodies to MenC and MenY polysaccharides. Anti-polyribosylribitol phosphate antibody concentrations were measured 1 month after the third dose. Safety was also assessed., Results: One month after primary vaccination statistically significantly more HibMenCY-TT than Hib-TT vaccines had anti-PRP antibody concentrations > or =1.0 microg/mL (93.5% vs. 85.8%). The percentage of HibMenCY-TT recipients with hSBA titers > or =1:8 (MenC: 95.9%, MenY: 89.4%) was statistically significantly higher than for MPSV4 recipients (MenC: 30.2%, MenY: 47.5%). The percentage of subjects reporting any severe (grade 3) symptom within 4 days of each vaccination was: 11.5% (HibMenCY-TT) and 24.8% (Hib-TT) (group difference, 13.27%, 95% CI: [7.22;19.29], P < 0.001)., Conclusion: The investigational HibMenCY-TT vaccine was well tolerated and immunogenic in infants, induced Hib immune responses that were comparable to licensed Hib-TT vaccine, and induced high levels of bactericidal antibodies against N. meningitidis serogroups C and Y.

A total of 465 children aged 8 to 10 years were vaccinated with 2 doses of Recombivax-HB 2.5 microg (RB) or Twinrix-Junior 10 microg/360 EL.U (TX), according to a 0 and 6 months schedule. Seven years postsecond dose, a challenge dose of vaccine was given. All vaccinees in the TX and 98% in the RB group showed an anamnestic response. Vaccination at the age of 8 to 10 years with two-pediatric doses of TX or RB given with a 6 months interval induces a long-lasting immunity in most vaccinees.

Background: This observational study evaluated a modified immunoprophylactic regimen (hepatitis B immune globulin [HBIG]) and a dose of thimerosal-free monovalent hepatitis B (HB) vaccine shortly after birth followed by doses of thimerosal-free bivalent Haemophilus influenzae type b (Hib)-HB vaccine at 2 and 4 months of age, and a booster at 12 months of age) in infants at high risk of hepatitis B virus (HBV) infection (mothers HBeAg+)., Methods: Children >or=6 months of age vaccinated in routine clinical practice were tested twice (>or=6 months apart) for HBV antigens surface antigen (HBsAg) and "e" antigen, and for antibody to HBsAg. Partial nucleotide sequence analysis was performed on HBV DNA isolated from infants identified with a breakthrough chronic HBV infection. A fully sequential statistical design was used to maximize patient safety and study efficiency., Results: Four of 60 children developed chronic HBV infection despite vaccination, but at no point did the cumulative number of cases reach the boundary of statistical significance. Overall, the analysis adjusted for sequential testing yielded an estimated breakthrough rate of 6.7% (90% CI: 2.3%-14.6%). In a subset of uninfected children tested for antibody to HBsAg 1 to 4 months after the second dose of Hib-HB vaccine, 90% (9/10) had >or=10 milli-International Units per milliliter (mIU/mL). The third dose of Hib-HB vaccine induced a secondary increase in the level of antibody; 94.7% (18/19) of a second group developed >or=100 mIU/mL, with a geometric mean concentration of 771 mIU/mL (95% CI: 351.4-1692.1 mIU/mL)., Conclusion: The tested regimen is comparably effective to historical experience with a standard one employing HBIG plus monovalent thimerosal-containing HB vaccine given at 0, 1, and 6 months of age.

Background: Immunogenicity of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine (PHiD-CV) was evaluated when coadministered with DTPw-HBV/Hib and OPV at 6, 10, and 14 weeks of age in the Philippines, or with DTPw-HBV/Hib and IPV at 2, 4, and 6 months of age in Poland., Methods: In this double-blind, controlled study (107007/NCT00344318), 400 Filipino and 406 Polish infants 6 to 12 weeks of age were randomized (3:1) to receive either PHiD-CV or the 7-valent pneumococcal conjugate vaccine (7vCRM). Immune responses were assessed 1 month post-dose III., Results: Percentages of infants with anti-pneumococcal antibody concentrations >or=0.2 microg/mL (GSK's 22F-inhibition ELISA) were within the same range for both pneumococcal conjugate vaccine groups, with the exception of serotypes 6B and 23F for which lower percentages were observed in the PHiD-CV group in Poland. At least 98.2% of PHiD-CV vaccinees had antibody concentrations >or=0.2 microg/mL against pneumococcal serotypes 1, 5, and 7F. In both countries, anti-pneumococcal antibody geometric mean concentrations against serotypes 18C and 19F were higher in the PHiD-CV group than in the 7vCRM group. Antibody geometric mean concentrations for most of the other common serotypes were within the same range for both groups in the Philippines and were lower in the PHiD-CV group in Poland. Functional responses (opsonophagocytic activity [OPA]) were observed for all vaccine serotypes in both countries., Conclusions: PHiD-CV was immunogenic against each of the 10 pneumococcal vaccine serotypes when coadministered with DTPw-HBV/Hib and poliovirus vaccines.

Background: The choice of non-typeable Haemophilus influenzae Protein D as main carrier protein in the candidate 10-valent pneumococcal conjugate vaccine (PHiD-CV, GlaxoSmithKline Biologicals), was driven in part to avoid carrier-mediated suppression and possible bystander interference with coadministered vaccines. Immunogenicity data from 3 primary and 2 booster vaccination studies were assessed for possible impacts of PHiD-CV coadministration on immune responses to routinely administered childhood vaccines, in comparison to 7-valent pneumococcal conjugate vaccine (7vCRM) coadministration., Methods: Randomized, controlled studies in which PHiD-CV or 7vCRM vaccines were coadministered with DTPa-[HBV]-IPV/Hib, DTPa-[HBV]-IPV, DTPw-HBV/Hib, IPV, and OPV, combined Hib-Neisseria meningitidis serogroup C vaccine (Hib-MenC-TT), standalone MenC-TT or MenC-CRM vaccines., Results: One month after primary vaccination, >96% of PHiD-CV recipients had seroprotective antibody concentrations against diphtheria, tetanus, poliovirus types 1 and 3, Hib (>or=0.15 microg/mL), SBA-MenC (>or=1:8), and >94% were seropositive for antibodies against pertussis antigens. Somewhat lower responses against poliovirus type 2 in study A (compared with poliovirus type 1 and 2 responses) and hepatitis B in the 6-, 10-, and 14-week schedule in the Philippines (compared with hepatitis B responses in the other studies) were observed after coadministration of both PHiD-CV and 7vCRM vaccines. Antitetanus and anti-PRP antibody geometric mean concentrations (GMCs) tended to be higher after PHiD-CV coadministration, probably because of the TT carrier protein for serotype 18C in PHiD-CV. Booster vaccination induced substantial increases in antibody GMCs for all coadministered antigens. These responses were generally within the same range in PHiD-CV and 7vCRM groups. Observed anti-PRP responses remained higher in PHiD-CV recipients after the booster dose., Conclusions: Coadministration of PHiD-CV with commonly used childhood vaccines induced high levels of seroprotection/seropositivity against all targeted diseases. No evidence of negative interference on the immune response to any of the coadministered vaccine antigens was observed when compared with the current routine practice of 7vCRM coadministration.

Background: The pentavalent rotavirus vaccine (PRV), RotaTeq, can be concomitantly administered with most routine childhood vaccines. This study evaluated the immunogenicity and reactogenicity of PRV when used concomitantly with a hexavalent vaccine containing diphtheria, tetanus, acellular pertussis, hepatitis B, inactivated poliovirus, and Haemophilus influenzae type b., Methods: Healthy infants (N = 403) received hexavalent vaccine concomitantly with either PRV or placebo at 2, 3, and 4 months of age. Antibody responses were measured immediately before and 42 +/- 3 days after vaccination. Parents/legal guardians recorded all adverse events for 14 days after vaccination., Results: Seroprotective titers for hepatitis B (hepatitis B surface antigen > or =10 mIU/mL) were achieved by 97.8% of subjects in both vaccine treatment groups. Seroprotective titers to H. influenzae type b (polyribosylribitol phosphate > or =0.15 microg/mL) were achieved by 91.4% of subjects receiving both vaccines and 95.1% of subjects receiving only hexavalent vaccine. Seroprotective titers to diphtheria, tetanus, and poliovirus were also comparable between the vaccine treatment groups, as were geometric mean antibody titers to the pertussis antigens. Among PRV recipients, 92% had a > or =3-fold rise in serum antirotavirus immunoglobulin A levels. Concomitant administration was well tolerated. The incidence of adverse events was similar for both groups, with no statistically significant increases in fever, vomiting, diarrhea, or irritability., Conclusions: In this study, concomitant administration of PRV with hexavalent vaccine was well tolerated and the immune responses to the antigens of the hexavalent vaccine were noninferior when compared with those of the control group. In addition, PRV was immunogenic when administered concomitantly with hexavalent vaccine.

Background: Use of combination vaccines has been associated with improved coverage rates, but their effect on timeliness remains to be explored. This study assessed the effect of diphtheria-tetanus-acellular pertussis/hepatitis B/inactivated polio vaccine (DTaP/HepB/IPV) on the timeliness of vaccine administration., Methods: This retrospective cohort study used administrative claims data from the Georgia Medicaid program. Children with 24 months of continuous enrollment and at least 4 vaccine-related office visits were stratified into 2 cohorts: those with at least 3 DTaP/HepB/IPV doses (DTaP/HepB/IPV cohort) and those with at least 3 doses of DTaP but no doses of DTaP/HepB/IPV (reference cohort). Children who received any dose of HepB/Hib were excluded to isolate the effect of the study vaccine. Timeliness was measured as the percentage of children who received their vaccines on time and the cumulative days undervaccinated., Results: There were 2880 children in the DTaP/HepB/IPV cohort and 2672 in the reference cohort. After controlling for covariates, receipt of DTaP/HepB/IPV was associated with significantly improved timeliness for 3 doses of DTaP (on-time rates: 66.3% vs. 60.8%, P < 0.0001; cumulative days undervaccinated: 29.5 vs. 70.4 days, P < 0.0001). Significantly improved timeliness was also observed in the DTaP/HepB/IPV cohort for IPV, HepB, Hib, 4 DTaPs, and the combination series assessed (P < 0.001 for all comparisons)., Conclusions: Use of DTaP/HepB/IPV in this Medicaid population was associated with improved on-time vaccination and fewer undervaccinated days. These findings, along with previous research associating combination vaccines with improved coverage rates, provide quantitative data to support the ACIP, AAP, and AAFP preference for combination vaccines.

Background: Studies of glycoconjugate vaccines have traditionally used an immune challenge with a plain polysaccharide vaccine to demonstrate immunologic memory. Plain polysaccharide vaccines are poorly immunogenic in children and can induce subsequent immunologic hyporesponsiveness. We therefore assessed the use of glycoconjugate vaccines as an alternative method of demonstrating immunologic memory., Methods: Children immunized with hepatitis B vaccine or serogroup C meningococcal glycoconjugate vaccine (MenCC) at age 2, 3, 4 months received a plain polysaccharide meningococcal serogroup A/C vaccine (MenACP) or MenCC at age 12 months. A post hoc analysis of serum bactericidal activity responses to MenCC assessed whether this differed in MenCC primed and MenCC naive infants., Results: MenCC primed children displayed higher geometric mean serum bactericidal titers than MenCC naive children following MenACP (1518 compared with 30; P = 0.003). A similar difference was seen after a dose of MenCC to toddlers (MenCC primed: 8663, MenCC naive: 710; P < 0.001). The latter comparison became a borderline significance after adjusting for higher pretoddler immunization serum bactericidal geometric mean titers in the MenCC primed group (P = 0.068)., Conclusions: Administration of glycoconjugate vaccines provides an important alternative method of demonstrating immunologic memory, avoiding the use of plain polysaccharide vaccines that are potentially deleterious in children. This has implications for the design of all future clinical trials of glycoconjugate vaccines.

Background: Long-term follow-up studies of populations that received recombinant hepatitis B (HB) vaccination beginning at birth are limited., Methods: Micronesian adolescents who had received 3 doses of recombinant HB vaccine (Recombivax 5 microg at birth, 2.5 microg at 2 months, 2.5 microg ug at 6 months) and tested negative for antibody to HB core antigen (anti-HBc) 2 years after primary vaccination (baseline testing) were followed up 15 years after primary vaccination. After testing for anti-HBc, HB surface antigen (HBsAg), and antibody to HBsAg (anti-HBs), participants received a booster dose of HB vaccine. An anamnestic response was defined as an increase in anti-HBs concentrations to a level > or = 10 mIU/mL 14 days postbooster., Results: Of the 105 participants, 42 (40.0%) had anti-HBs concentrations > or = 10 mIU/mL on baseline testing. At 15 years, 8 (7.6%) were anti-HBc positive; none were HBsAg positive. Of the remaining 97, 7 (7.3%) had anti-HBs concentrations > or = 10 mIU/mL. Of the 96 who received a booster dose, 46 (47.9%) had an anamnestic response; final antibody concentrations were 10-99 mIU/mL for 17 (17.7%) and > 100 mIU/mL for 29 (30.2%). Participants with anti-HBs concentrations > or = 10 mIU/mL on baseline testing were more likely to have an anamnestic response at 15 years [26/39 (66.7%) versus 20/57 (35.1%); P = 0.003]., Conclusions: Fifteen years after primary vaccination starting at birth, 8% of participants had evidence of past HB virus infection, but none had chronic infection. Absence of an anamnestic response to an additional vaccine dose, seen in half of participants, might indicate waning immunity.

Despite the availability of safe and effective hepatitis B virus (HBV) vaccines for >20 years, strategies targeting risk groups failed to sufficiently control hepatitis B disease at the population level; this is mainly because of difficulties in risk identification and in program implementation. Hence, the global burden of disease of HBV still is substantial. The World Health Organization recommends universal vaccination against hepatitis B to ultimately eliminate HBV; this recommendation had been progressively implemented to reach 168 countries with a universal program by the end of 2006. However, hepatitis B immunization is currently becoming endangered of losing its place on the agendas of governments, agencies, and international organizations, mainly because of the increasing success of these immunization programs and the interest in newer vaccine-preventable diseases and the related programs.This publication aims to show that vaccination programs targeting newborns and infants are preferable to achieve this goal. The benefits of universal HBV vaccination for newborns and infants are: higher impact on chronic carrier rate and transmission; established potential of high vaccine coverage in this age group; opportunities to combine HBV vaccination with existing universal vaccination programs for newborns and infants; and impact on perinatal transmission, if vaccination is started shortly after birth. Moreover, the safety, immunogenicity, and long-term efficacy of newborn and infant HBV vaccination have been proven extensively. In summary, newborn and infant HBV vaccination programs should be considered the preferred strategy, capable of providing important and sustained impact on global HBV incidence, even if they have a delayed impact on sexual transmission of HBV.

Background: A live pentavalent rotavirus vaccine (PRV) containing 5 human-bovine (WC3) reassortants expressing human serotypes G1, G2, G3, G4 and P1A[8] was evaluated in a blinded, placebo-controlled study. Possible interactions between PRV and concomitantly administered licensed pediatric vaccines were investigated in a United States-based nested substudy (Concomitant Use Study) of the Rotavirus Efficacy and Safety Trial., Methods: From 2002 to 2003, healthy infants approximately 6 to 12 weeks of age at entry were randomized to receive either 3 oral doses of PRV or placebo at 4- to 10-week intervals. Subjects were also to receive combined Haemophilus influenzae type b and hepatitis B vaccine (2 doses), diphtheria and tetanus toxoids and acellular pertussis vaccine (3 doses), inactivated poliovirus vaccine (2 doses) and pneumococcal conjugate vaccine (3 doses) on the same day; oral poliovirus vaccine was not administered. Immunogenicity was assessed by measuring antibody responses to PRV and antigens contained in the licensed vaccines. Cases of rotavirus gastroenteritis were defined by forceful vomiting and/or -3 watery or looser-than-normal stools within a 24-hour period, and detection of rotavirus antigen in the stool. Safety was assessed by reporting of adverse events using diary cards., Results: The Concomitant Use Study enrolled 662 subjects in the PRV group and 696 subjects in the placebo group. For the 17 antigens in the concomitantly administered vaccines, antibody responses were similar in PRV and placebo recipients, except for moderately diminished antibody responses to the pertactin component of pertussis vaccine. Efficacy of PRV against rotavirus gastroenteritis of any severity was 89.5% (95% CI = 26.5-99.8%). PRV was generally well tolerated when given concomitantly with the prespecified vaccines., Conclusions: In this study, antibody responses to the concomitantly administered vaccines were generally similar in PRV and placebo recipients. PRV was efficacious and well tolerated when given concomitantly with pediatric vaccines licensed in the United States.

Children 17-20 months of age (N = 344) received a diphtheria-tetanus toxoids-acellular pertussis (DTPa)-inactivated poliovirus vaccine (IPV)/Haemophilus influenzae (Hib) booster after a 3-dose primary vaccination course with DTPa-hepatitis B vaccine-IPV/Hib plus conjugate meningococcal C vaccine-CRM. Seroprotection rates were >80% (diphtheria, tetanus, hepatitis B, polio and polyribosylribitol phosphate) before and > or =96.6% (diphtheria, tetanus, polio and polyribosylribitol phosphate) after booster vaccination. The booster was well-tolerated (fever >39.5 degrees C after <2% of doses; large swelling reactions after 6.3% of doses).