Safety and immunogenicity of 3 formulations of a Sabin inactivated poliovirus vaccine produced on the PER.C6® cell line: A phase 2, double-blind, randomized, controlled study in infants vaccinated at 6, 10 and 14 weeks of age.

An inactivated poliovirus vaccine candidate using Sabin strains (sIPV) grown on the PER.C6® cell line was assessed in infants after demonstrated immunogenicity and safety in adults. The study recruited 300 infants who were randomized (1:1:1:1) to receive one of 3 dose levels of sIPV or a conventional IPV based on Salk strains (cIPV). Poliovirus-neutralizing antibodies were measured before the first dose and 28 days after the third dose. Reactogenicity was assessed for 7 days and unsolicited adverse events (AEs) for 28 days after each vaccination. Serious AEs (SAEs) were recorded throughout the study. Solicited AEs were mostly mild to moderate. None of the SAEs reported in the study were judged vaccine related, including one fatal SAE due to aspiration of vomitus that occurred 26 days after the third dose of low-dose sIPV. After 3 sIPV vaccinations and across all dose levels, seroconversion (SC) rates were at least 92% against Sabin poliovirus types and at least 80% against Salk types, with a dose-response in neutralizing antibody geometric mean titers (GMTs) observed across the 3 sIPV groups. Compared to cIPV, the 3 sIPV groups displayed similar or higher SC rates and GMTs against the 3 Sabin types but showed a lower response against Salk types 1 and 2; this was most visible for Salk type 1. While the PER.C6® cell line-based sIPV showed an acceptable safety profile and immunogenicity in infants, lower seroprotection against type 1 warrants optimization of dose level and additional clinical evaluation.

Meeting report: CEPI consultation on accelerating access to novel vaccines against emerging infectious diseases for pregnant and lactating women, London, 12-13 February 2020.

Infectious diseases may cause serious morbidity and mortality in pregnant women, their foetuses, and infants; the risk associated with any newly emerging infectious disease (EID) is likely unknown at the time of its emergence. While the ongoing SARS-CoV-2 pandemic shows that the development of vaccines against new pathogens can be considerably accelerated, the immunization of pregnant women generally lags behind the general population. Guided by the priority pathogen list for WHO's R&D Blueprint for Action to Prevent Epidemics, this workshop sought to define the evidence needed for use of vaccines against EIDs in pregnant and lactating women, using Lassa fever as a model. Close to 60 maternal immunization (MI) and vaccine safety experts, regulators, vaccine developers, Lassa fever experts, and investigators from Lassa-affected countries examined the critical steps for vaccine development and immunization decisions for pregnant and lactating women. This paper reports on key themes and recommendations from the workshop. Current practice still assumes the exclusion of pregnant women from early vaccine trials. A shift in paradigm is needed to progress towards initial inclusion of pregnant women in Phase 2 and 3 trials. Several practical avenues were delineated. Participants agreed that vaccine platforms should be assessed early for their suitability for maternal immunization. It was noted that, in some cases, nonclinical data derived from assessing a given platform using other antigens may be adequate evidence to proceed to a first clinical evaluation and that concurrence from regulators may be sought with supporting rationale. For clinical trials, essential prerequisites such as documenting the disease burden in pregnant women, study site infrastructure, capabilities, and staff experience were noted. Early and sustained communication with the local community was considered paramount in any program for the conduct of MI trials and planned vaccine introduction.

Safety and immunogenicity of a new Sabin inactivated poliovirus vaccine candidate produced on the PER.C6® cell-line: a phase 1 randomized controlled trial in adults.

This first-in-human study (NCT03032588), conducted in Belgium, evaluated a new inactivated poliovirus vaccines (IPV) candidate based on Sabin poliovirus strains grown on the high-yield PER.C6® cell line. Healthy adults (N = 32) were randomized (1:1) to receive a single dose of PER.C6-based Sabin-IPV (sIPV, 15:35:112.5 DU/dose) or conventional Salk-IPV (cIPV, 40:8:32 DU/dose). Reactogenicity was assessed up to 7 days after vaccination, immunogenicity 28 days after vaccination, and safety up to 6 months after vaccination.Solicited adverse events (AEs) were mild to moderate, no changes of concern in vital signs or safety laboratory values were observed, and no severe AEs (SAEs) or vaccine-related unsolicited AEs were reported after vaccination. A trend to more frequent solicited AEs after sIPV than after cIPV administration was observed. Most participants had preexisting neutralizing antibodies against poliovirus types (titer ≥8), which were strongly boosted by sIPV. Post-vaccination geometric mean titers were high (≥12,000) and similar across the two vaccination groups. Only participants with very high preexisting antibody levels did not show a vaccine-induced response, defined in seropositive participants as a 4-fold titer increase. The 10 initially seronegative (titer <8) participants (n = 5 in each study group) seroconverted and all participants had seroprotective antibody levels post-vaccination. The antibodies elicited by sIPV neutralized both Sabin and Salk poliovirus strains.In conclusion, the PER.C6®-based sIPV was well tolerated and highly immunogenic in adults with preexisting antibodies to poliovirus.

Long-term anti-HBs antibody persistence and immune memory in children and adolescents who received routine childhood hepatitis B vaccination.

This paper presents data from two studies that evaluated 5-y and 10-y persistence of antibodies against hepatitis B (HBV) surface antigen (anti-HBs) and immune response to an HBV vaccine challenge in children and adolescents who had received three doses of a HBV vaccine in infancy as part of routine clinical practice [NCT00519649/NCT00984139]. Anti-HBs antibody concentrations ≥ 10 mIU/ml persisted in 83.3% (95% confidence interval [CI]: 78.5­87.5) and 78.3% (95% CI: 73.1­83.0) of subjects aged 7­8 y and 12­13 y, respectively 5­10 y after infant vaccination. One month postchallenge dose, 98.2% (95% CI: 95.9­99.4) and 93.7% (95% CI: 90.2­96.2) of subjects in the two age groups, respectively had anti-HBs antibody concentrations ≥ 100 mIU/ml. Overall, 99.6% (95% CI: 98­100) and 97.2% (95% CI: 94.5­98.8) of subjects aged 7­8 y and 12­13 y mounted an anamnestic response to the HBV challenge dose, which was well-tolerated. Healthy children aged 7­8 y and adolescents aged 12­13 y received three doses of a monovalent pediatric HBV vaccine (10 µg of HBsAg) before 18 mo of age. Serum samples collected before and one month post-HBV vaccine challenge dose were tested for anti-HBs antibody concentrations. Safety assessments were made for the HBV vaccine challenge dose. A three-dose childhood HBV immunization regimen induced persistence of antibodies against HBV infection for 10 y, up to adolescence. This vaccination regimen also conferred long-term immune memory against HBV as evidenced by the strong anamnestic response to the HBV vaccine challenge, despite waning anti-HBs antibody levels.

Antibody persistence and immune memory in healthy adults following vaccination with a two-dose inactivated hepatitis A vaccine: long-term follow-up at 15 years.

Long-term persistence of vaccine-induced immune response in adults was assessed annually for 15 years following primary immunization with a two-dose inactivated hepatitis A vaccine. In 1992, 119 and 194 subjects aged 17-40 years and naïve for hepatitis A virus (HAV) were enrolled in two studies to receive 1,440 ELISA units (El.U) of inactivated hepatitis A vaccine (Havrix™, GlaxoSmithKline Biologicals, Belgium) according to a standard 0, 6 or an extended 0, 12 months schedule, respectively. Serum samples were taken 1 month after the second vaccine dose and every consecutive year up to 15 years after primary vaccination for measurement of anti-HAV antibody concentrations (NCT00291876 and NCT00289757). At year 15, 100% (48/48) and 97.3% (108/111) of subjects vaccinated at 0, 6 or 0, 12 months remained seropositive for anti-HAV antibodies, with geometric mean concentrations (GMCs) of 289.2 and 367.4 mIU/ml, respectively. An additional dose of HAV vaccine (1,440 El.U) was administered to the six subjects who had become seronegative for anti-HAV antibodies since year 11. All subjects mounted a humoral immune response to the additional HAV challenge dose, although post-challenge anti-HAV antibody levels remained low in one subject. These studies represent the longest annual follow-up of hepatitis A vaccine in healthy adults. The immune response induced by two doses of this inactivated HAV vaccine was shown to persist for at least 15 years. No difference in long-term antibody persistence was observed between the two primary vaccination schedules, reinforcing the potential for flexibility in the timing of the second primary vaccine dose.

Immunogenicity of the reduced-antigen-content dTpa vaccine (Boostrix(®)) in adults 55 years of age and over: a sub-analysis of four trials.

BACKGROUND: Older adults, especially those over 65 years, are at risk of more severe morbidity from diphtheria, tetanus and pertussis and may transmit pertussis to unvaccinated or not yet fully vaccinated infants, but data on their response to reduced-antigen-content tetanus, diphtheria and acellular pertussis (dTpa) vaccines are lacking. METHODS: A sub-analysis pooled immunogenicity results in 293 adults aged 55+ years (mean age 64.4 years) from four randomised, controlled clinical trials of dTpa vaccine (Boostrix(®), GlaxoSmithKline Biologicals) with or without IPV co-administration, or dTpa-IPV (Boostrix(®) IPV). RESULTS: Seroprotective antibody levels were achieved by 82.8% for diphtheria and 94.5% for tetanus. For pertussis antigens, the booster response rate, defined as initially seronegative subjects [<5EU/mL] reaching ≥5EU/mL; or a ≥2-fold increase in antibody concentration if initially seropositive was 89.2% for pertussis toxoid, 95.8% for filamentous haemagglutinin and 94.5% for pertactin. Post-booster geometric mean concentrations (GMC) increased for all antigens. Post-booster anti-tetanus and anti-PRN GMCs tended to be higher in 55- to 64-year olds than in those aged 65+. CONCLUSION: Larger numbers of subjects over 75 years are needed to better define responses in advanced age, but these data suggest that a single booster dose of dTpa or dTpa-IPV induces good immunological responses in most, and that these vaccines could be readily integrated into existing programmes.

Antibody persistence and immune memory 4 years post-vaccination with combined hepatitis A and B vaccine in adults aged over 40 years.

Persistence of immune response was assessed in adults aged >40 years (N = 596) following primary vaccination with combined hepatitis A/B vaccine or concomitant monovalent hepatitis A and B vaccines. Anti-hepatitis A virus antibody responses persisted for at least 4 years regardless of the vaccine used, with anti-hepatitis B surface antibody responses higher and more sustained in subjects who received the combined hepatitis A/B vaccine. Response rates to an additional dose of the same vaccine(s) used for priming were high.

Long-term immunogenicity and immune memory after two doses of the adult formulation of a combined hepatitis A and B vaccine in children 1 to 11 years of age.

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.

Five years follow-up following two or three doses of a hepatitis B vaccine in adolescents aged 11-15 years: a randomised controlled study.

BACKGROUND: The standard three-dose schedule of hepatitis B vaccines is frequently not completed, especially in adolescents. A primary study has confirmed the equivalence of a two-dose schedule of an Adult formulation of hepatitis B vaccine [Group HBV_2D] to a three-dose schedule of a Paediatric formulation in adolescents (11-15 years) [Group HBV_3D]. This follow-up study evaluated the five year persistence of antibody response and immune memory against the hepatitis B surface (anti-HBs) antigens five years after completion of primary vaccination. METHODS: A total of 234 subjects returned at the Year 5 time point, of which 144 subjects received a challenge dose of hepatitis B vaccine. Blood samples were collected yearly and pre- and post-challenge dose to assess anti-HBs antibody concentrations. RESULTS: At the end of five years, 79.5% (95% confidence interval [CI]: 71.7 - 86.1) and 91.4% (95% CI: 82.3 - 96.8) of subjects who received the two-dose and three-dose schedules, respectively had anti-HBs antibody concentrations ≥ 10 mIU/mL. Post-challenge dose, all subjects had anti-HBs antibody concentration ≥ 10 mIU/mL and >94% subjects had anti-HBs antibody concentration ≥ 100 mIU/mL. All subjects mounted a rapid anamnestic response to the challenge dose. Overall, the challenge dose was well-tolerated. CONCLUSION: The two-dose schedule of hepatitis B vaccine confers long-term immunogenicity and shows evidence of immune memory for at least five years following vaccination. TRIAL REGISTRATION: Clinical Trials NCT00343915, NCT00524576.

Primary and booster vaccination in Latin American children with a DTPw-HBV/Hib combination: a randomized controlled trial.

BACKGROUND: Diphtheria-tetanus-whole-cell pertussis (DTPw)-based combination vaccines are an attractive option to rapidly achieve high coverage and protection against other important pathogens, such as hepatitis B virus (HBV) and Haemophilus influenzae type B (Hib). To ensure adequate antigen supply, GlaxoSmithKline Biologicals has introduced a new DTPw antigen source and developed a new DTPw-HBV/Hib combination vaccine containing a reduced amount of Hib polyribosylribitol phosphate (PRP). This study was undertaken to compare the immunogenicity and reactogenicity of this new DTPw-HBV/Hib vaccine with a licensed DTPw-HBV/Hib vaccine (Tritanrix™-HBV/Hib). METHODS: This was a randomized, partially-blind, multicenter study in three countries in Latin America (Argentina, Chile and Nicaragua). Healthy children received either the new DTPw-HBV/Hib vaccine (1 of 3 lots; n = 439; double-blind) or Tritanrix™-HBV/Hib (n = 146; single-blind) co-administered with oral poliovirus vaccine (OPV) at 2, 4 and 6 months, with a booster dose at 18-24 months. RESULTS: One month after the end of the 3-dose primary vaccination course, the new DTPw-HBV/Hib vaccine was non-inferior to Tritanrix™-HBV/Hib in terms of seroprotection/vaccine response rates for all component antigens; ≥97.3% and ≥93.9% of subjects in the two groups, respectively, had seroprotective levels of antibodies against diphtheria, tetanus, hepatitis B and Hib and a vaccine response to the pertussis component. Persistence of antibodies against all vaccine antigens was comparable between groups, with marked increases in all antibody concentrations after booster administration in both groups. Both vaccines were generally well-tolerated as primary and booster doses. CONCLUSIONS: Results confirm the suitability of this new DTPw-HBV/Hib vaccine comprising antigens from a new source and a reduced PRP content for inclusion into routine childhood vaccination programs. TRIAL REGISTRATION: http://www.clinicaltrials.gov NCT00332566.

The immunogenicity and safety of a reduced PRP-content DTPw-HBV/Hib vaccine when administered according to the accelerated EPI schedule.

BACKGROUND: Combination vaccines improve coverage, compliance and effectively introduce new antigens to mass vaccination programmes. This was a phase III, observer-blind, randomized study of GSK Biologicals diphtheria-tetanus-whole cell pertussis vaccine combined with hepatitis B and Haemophilus influenzae type b vaccines, containing a reduced amount of polyribosyl-ribitol-phosphate (PRP) and a DTPw component manufactured at a different site (DTPw-HBV/Hib2.5 [Kft]). The primary aim of this study was to demonstrate that DTPw-HBV/Hib2.5 [Kft] was not inferior to the licensed DTPw-HBV/Hib (Tritanrix(tm)-HepB/Hiberix(tm)) vaccine or the DTPw-HBV/Hib2.5 vaccine, also containing a reduced amount of PRP, with respect to the immune response to the PRP antigen, when administered to healthy infants, according to the Expanded Programme for Immunization (EPI) schedule at 6, 10 and 14 weeks of age. METHODS: 299 healthy infants were randomised to receive either DTPw-HBV/Hib2.5 [Kft] DTPw-HBV/Hib2.5 or DTPw-HBV/Hib according to the 6-10-14 week EPI schedule. Blood samples were analysed prior to the first dose of study vaccine and one month after the third vaccine dose for the analysis of immune responses. Solicited local and general symptoms such as pain, redness and swelling at the injection site and drowsiness and fever, unsolicited symptoms (defined as any additional adverse event) and serious adverse events (SAEs) were recorded up to 20 weeks of age. RESULTS: One month after the third vaccine dose, 100% of subjects receiving DTPw-HBV/Hib2.5 [Kft] or DTPw-HBV/Hib and 98.8% of subjects receiving DTPw-HBV/Hib2.5 vaccine had seroprotective levels of anti-PRP antibodies (defined as anti-PRP antibody concentration ≥0.15 µg/ml). Seroprotective antibody concentrations were attained in over 98.9% of subjects for diphtheria, tetanus and hepatitis B. The vaccine response rate to pertussis antigen was at least 97.8% in each group. Overall, the DTPw-HBV/Hib2.5 [Kft] vaccine was well tolerated in healthy infants; no SAEs were reported in any group. CONCLUSIONS: The DTPw-HBV/Hib2.5 [Kft] vaccine was immunogenic and well-tolerated when administered according to the EPI schedule to Indian infants. TRIAL REGISTRATION: http://www.clinicaltrials.gov NCT00473668.

A decennial booster dose of reduced antigen content diphtheria, tetanus, acellular pertussis vaccine (Boostrix™) is immunogenic and well tolerated in adults.

Reduced-antigen-content diphtheria-tetanus-acellular-pertussis (dTpa) vaccines are predominantly recommended for once-in-a-lifetime use. A second dTpa (Boostrix™, GlaxoSmithKline Biologicals) administration in 164 adults previously vaccinated with dTpa 10 years previously was evaluated. Before the decennial booster, 89.4% and 94.8% subjects were seroprotected (antibodies ≥0.1 IU/mL) for diphtheria and tetanus, respectively. One-month post-booster, all subjects were seroprotected/seropositive against all vaccine antigens. Robust GMC increases indicated a booster response similar to the first booster. The decennial booster was well tolerated without serious adverse events, consistent with product experience. This study supports replacing traditional Td boosters with dTpa, and use of Boostrix™ as a decennial booster. This study is registered at www.clinicaltrials.com NCT00548171.

Decennial administration of a reduced antigen content diphtheria and tetanus toxoids and acellular pertussis vaccine in young adults.

BACKGROUND: Booster vaccination against tetanus and diphtheria at 10-year intervals is commonly recommended. Reduced antigen content diphtheria and tetanus toxoids and acellular pertussis (dTpa) vaccines developed for booster vaccination of preschool children, adolescents, and adults are licensed for once-in-a-lifetime use in most countries. Objective. To evaluate decennial administration of a dTpa vaccine. Methods. Young adults vaccinated with dTpa or diphtheria and tetanus toxoids followed by acellular pertussis (DT+ap) 1 month later in a clinical trial 10 years previously received 1 dTpa dose. Blood samples were taken before and 1 month after vaccination. Antibody concentrations against vaccine antigens were measured by enzyme-linked immunosorbent assay. Solicited and unsolicited symptoms and serious adverse events were recorded. RESULTS: Eighty-two individuals were enrolled in the study. In the 75 individuals who had received the dTpa vaccine 10 years previously, prevaccination seroprotection or seropositivity rates were 98.8% (diphtheria), 97.5% (tetanus), 64.6% (pertussis toxoid), 100% (filamentous hemagglutinin), and 96.3% (pertactin). One month after the second booster, all study participants were seroprotected or seropositive against all vaccine antigens. Antibody concentrations increased by a similar magnitude as 10 years previously. During the 4-day follow-up, 9.9% of participants recorded grade 3 pain; 17.3% and 18.5% recorded redness and swelling of 50 mm or larger, respectively; and 8.6% recorded fever (temperature, 37.5 degrees C). No serious adverse events were considered causally related to the vaccine. CONCLUSIONS: A second dTpa booster was highly immunogenic and well tolerated in this population of young adults. This study supports the use of this vaccine as a decennial booster. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00610168 .

Comparison of long-term (10 years) immunogenicity of two- and three-dose regimens of a combined hepatitis A and B vaccine in adolescents.

300 adolescents aged 12-15 years were randomised (1:1) into two groups to compare the long-term (10 years) immunogenicity profile of two doses of an Adult formulation [Group HAB_2D: 150; 0-6 months] vs. three doses of a Paediatric formulation [Group HAB_3D: 150; 0-1-6 months] of a combined hepatitis A and B (HAB) vaccine. At Year 10, anti-HAV seropositivity rate was 100% in both groups, while 85.9% and 85.1% subjects in the HAB_2D and HAB_3D groups, respectively, had anti-HBs antibody concentrations > or =10 mIU/mL. The anti-HAV antibody GMCs (HAB_2D: 429.3 mIU/mL; HAB_3D: 335.5 mIU/mL) and anti-HBs antibody GMCs (HAB_2D: 50.6 mIU/mL; HAB_3D: 60.1 mIU/mL) were similar in both groups. No vaccine-related serious adverse events were reported. Hence, with respect to long-term antibody persistence, the two-dose schedule of the combined HAB vaccine Adult formulation is an effective alternative to the conventional three-dose schedule of the Paediatric formulation in adolescents.

Long-term (5-year) antibody persistence following two- and three-dose regimens of a combined hepatitis A and B vaccine in children aged 1-11 years.

This study compared the long-term persistence of anti-hepatitis A (anti-HAV) and B (anti-HBs) antibodies, 5 years after vaccination of subjects aged 1-11 years with a combined hepatitis A and B vaccine either in a two-dose (0, 6 months, Adult formulation) or a three-dose (0, 1, 6 months, Paediatric formulation) schedule. At the end of the 5 years, all subjects (100%) in both groups continued to have anti-HAV antibodies > or =15mIU/mL, while 94-97% of subjects in both groups had anti-HBs antibody concentrations > or =10mIU/mL. Subjects with anti-HBs antibody concentration < or =10mIU/mL were administered a challenge dose of hepatitis B vaccine. All subjects mounted a vigorous immune response to the challenge indicating the presence of immunological memory to HBV.

Booster vaccination after neonatal priming with acellular pertussis vaccine.

After a birth dose of acellular pertussis (aP) and diphtheria (DT)aP-hepatitis B virus (HBV)-inactivated polio vaccine (IPV)/Haemophilus influenza type b (Hib) at 2, 4, and 6 months, a booster dose of DTaP-HBV-IPV/Hib at 12 to 23 months induced strong anti-pertussis booster responses. Thus, neonatal aP priming did not lead to immune tolerance to pertussis antigens. However, it elicited bystander interference on HBV, Hib, and diphtheria responses.

Lasting immune memory against hepatitis B in children after primary immunization with 4 doses of DTPa-HBV-IPV/Hib in the first and 2nd year of life.

BACKGROUND: Few studies have assessed long term persisting immunity against hepatitis B virus (HBV) in children vaccinated during infancy with combined vaccines containing recombinant HBV surface antigen (HBs). We assessed antibody persistence and immune memory in children 4-5 years of age, previously vaccinated with four doses of combined hexavalent DTPa-HBV-IPV/Hib vaccine (Infanrix hexa). METHODS: Immune memory was assessed in 301 children through administration of a challenge dose of monovalent HBV vaccine. RESULTS: At 4-5 years of age, 85.3% of subjects had persisting anti-HBs antibody concentrations >or= 10 mIU/mL, rising to 98.6% after the HBV challenge dose. All but 12 subjects (95.8%) achieved post-challenge anti-HBs concentrations >or= 100 mIU/mL. The post-challenge anti-HBs GMC rose by 100-fold compared to pre-challenge concentrations. An anamnestic response to the HBV vaccine challenge was observed in 96.8% of subjects, including 17/21 (81.0%) of children with initially undetectable antibodies (<3.3 mIU/mL). All but 4 of 42 subjects (90.5%) with anti-HBs antibodies <10 mIU/mL prior to the challenge dose, achieved seroprotective levels afterwards. A 4-fold rise in antibody concentration after the challenge dose was observed in 259/264 (98.1%) of initially seropositive subjects. The magnitude of the post-challenge responses was proportional to pre-challenge anti-HBs levels. No serious adverse events were reported during the study. CONCLUSION: The combined DTPa-HBV-IPV/Hib vaccine induced lasting immune memory against hepatitis B. Long term protection afforded by DTPa-HBV-IPV/Hib is likely to be similar to that observed following priming with monovalent HBV vaccines. TRIAL REGISTRATION: http://www.clinicaltrials.gov 106789 NCT00411697.

Persistence of antibodies and immune memory to hepatitis B vaccine 20 years after infant vaccination in Thailand.

Booster vaccination against hepatitis B (HBV) is not currently recommended, although debate continues on the duration of protection after priming. We assessed antibody persistence and immune memory to hepatitis B 20 years after priming with a recombinant HBV-vaccine during infancy. Infants were vaccinated at birth, 1, 2 and 12 months of age. A subset received a booster dose at Year 5. Antibody persistence was measured approximately yearly until Year 20. Immune memory was assessed by administration of HBV booster dose. At Year 20, anti-HBs seroprotection rates and GMCs tended to be higher in Year 5 boosted than unboosted recipients (83.9% versus 60.5%). After the Year 20 booster dose, anti-HBs anamnestic responses were within the same range 95.8% of subjects in both groups. Primary and booster vaccination with HBV-vaccine in infants induces sustained seroprotection and immune memory against hepatitis B for up to 20 years. Higher persisting seroprotection rates in subjects boosted at Year 5 did not translate into apparent differences in immune memory in a high endemic country.

Immunological persistence in 4-6 and 7-9 year olds previously vaccinated in infancy with hexavalent DTPa-HBV-IPV/Hib.

BACKGROUND: The combined diphtheria-tetanus-pertussis-hepatitis B-inactivated poliomyelitis-Haemophilus influenzae conjugate vaccine (DTP a-HBV-IPV/Hib, Infanrix Hexa() GlaxoSmithKline Biologicals, Rixensart, Belgium) is the only hexavalent vaccine currently licensed for primary and booster vaccination of infants and provides simultaneous protection against six major diseases of childhood. The persistence of the immune response in children aged 4-6 and 7-9 years of age previously vaccinated with four doses of DTP a-HBV-IPV/Hib vaccine was assessed (www.clinicaltrials.gov.au 106744 NCT00356564 and 106745 NCT00335881). METHODS: A blood sample was collected from 403 children, all of whom had received 3-dose primary vaccination and a booster dose in the second year of life with DTP a-HBV-IPV/Hib, in previous clinical vaccine trials in Germany. RESULTS: Mean time from the fourth DTP a-HBV-IPV/Hib dose until serological follow-up ranged between 3.6 and 6.4 years. After the 4th DTP a-HBV-IPV/Hib dose, in subjects who had not received additional booster doses, seroprotective antibody levels persisted up to 9 years of age in >/=90% of subjects for diphtheria, Hib and poliomyelitis, in 77.2% subjects for Hepatitis B and in 64.7% of subjects for tetanus. Anti-pertussis toxin antibodies remained detectable in no more than 38.2% of subjects. CONCLUSION: With the exception of PT , the combined DTP a-HBV-IPV/Hib induces long lasting immune response against all vaccine antigens. Falling seropositivity against PT over time supports the recommended administration of a pertussis booster dose in 5-6 year old children in Germany.

Review of 8 years of experience with Infanrix hexa (DTPa-HBV-IPV/Hib hexavalent vaccine).

Combination vaccines that include multiple antigens within one formulation are now widely accepted as an effective means of eliciting protection against several diseases at the same time. Owing to improvements in quality and convenient modes of administration, they have become part of routine pediatric practice. Hexavalent vaccines, including diphtheria, tetanus, pertussis, hepatitis B, polio and Haemophilus influenzae type b antigens represent the latest advance in the development of combination vaccines. Over 8 years since its first licensure, this review looks at the immunogenicity, efficacy and safety profile of the only hexavalent pediatric vaccine currently in use--Infanrix hexa (diphtheria, tetanus, acellular pertusis-hepatitis B virus-inactivated poliovirus vaccine/Haemophilus influenzae type b vaccine [DTPa-HBV-IPV/Hib]; GlaxoSmithKline Biologicals, Rixensart, Belgium)--through published clinical trials and postmarketing surveillance data. These data show DTPa-HBV-IPV/Hib to be highly immunogenic and well tolerated across a range of different primary and booster vaccination schedules, as well as when administered concomitantly with other licensed vaccines (e.g., pneumococcal conjugate vaccine). Additional issues surrounding the use of hexavalent vaccines are also reviewed.