Modeling the Long-term Antibody Response and Duration of Immune Protection Induced by an Inactivated, Preservative-free Hepatitis A Vaccine (Healive) in Children / 生物医学与环境科学（英文）

Objective@#Long-term seroprotection the hepatitis A vaccine is essential for the prevention of disease from the hepatitis A virus (HAV). Due to documented difficulties during decade-long follow-ups after receiving vaccines, statistical-modeling approaches have been applied to predict the duration of immune protection.@*Methods@#Based on five-year follow-up data from a randomized positive-controlled trial among Chinese children (1-8 years old) following a 0, 6 months vaccination schedule, a power-law model accounting for the kinetics of B-cell turnover, as well as a modified power-law model considering a memory-B-cell subpopulation, were fitted to predict the long-term immune responses induced by HAV vaccination (Healive or Havrix). Anti-HAV levels of each individual and seroconversion rates up to 30 years after vaccination were predicted.@*Results@#A total of 375 participants who completed the two-dose vaccination were included in the analysis. Both models predicted that, over a life-long period, participants vaccinated with Healive would have close but slightly higher antibody titers than those of participants vaccinated with Havrix. Additionally, consistent with previous studies, more than 90% of participants were predicted to maintain seroconversion for at least 30 years. Moreover, the modified power-law model predicted that the antibody titers would reach a plateau level after nearly 15 years post-vaccination.@*Conclusions@#Based on the results of our modeling, Healive may adequately induce long-term immune responses following a 0, 6 months vaccination schedule in children induction of memory B cells to provide stable and durable immune protection.

One-year antibody persistence and safety of a 4-dose schedule of MenACWY-CRM in healthy infants from South Korea

PURPOSE: Results from a post-marketing study to generate evidence on 1-year antibody persistence and safety following vaccination of infants from South Korea with the quadrivalent meningococcal conjugate vaccine MenACWY-CRM. MATERIALS AND METHODS: In this phase IV, open-label, multi-center study (NCT02446691), 128 infants received MenACWY-CRM at ages 2, 4, 6, and 12 months. One-year antibody persistence following the full vaccination course was evaluated (primary objective) for the four meningococcal serogroups (Men) by serum bactericidal activity assay using human or rabbit complement (hSBA/rSBA). Immune responses at 1-month post-vaccination and safety were also assessed. RESULTS: The percentage of children with hSBA titers ≥8 ranged between 94% (MenA) and 100% (MenY/W) 1-month post-vaccination, and from 39% (MenA) to 89% (MenY) 1-year post-vaccination. At least 99% and 92% of children had rSBA titers ≥8 and ≥128 against each meningococcal serogroup, 1-month post-vaccination. One-year post-vaccination, the percentage of children with rSBA titers ≥8 and ≥128 ranged from 54% (MenC) to 99% (MenA) and from 30% (MenC) to 98% (MenA). Geometric mean titers declined from 1-month to 1-year post-vaccination, when they varied between 6.8 (MenA) and 53.6 (MenW) by hSBA and between 17.2 (MenC) and 2,269.5 (MenA) by rSBA. At least one solicited and unsolicited adverse event was reported for 79% and 66% of children. Of 36 serious adverse events reported, none were vaccination-related. CONCLUSION: Antibody persistence (hSBA/rSBA titers ≥8) was determined in 39%–99% of children 1 year after a 4-dose MenACWY-CRM series during infancy, with an acceptable clinical safety profile.

Comparison of antibody persistence after primary immunization with 5 μg and 10 μg recombinant hepatitis B vaccine among newborns with normal and high response: a five-year following-up / 中华流行病学杂志

Objective To compare the antibody persistence 5 years after primary immunization with 5 μg and 10 μg recombinant hepatitis B vaccine (HepB) among newborns with normal and high response.Methods Newborns who completed three doses of 5 μ g HepB made by recombinant dexyribonucleic acid technique in Saccharomyces (HepB-SC) or 10 μg HepB made by recombinant dexyribonucleic acid technique in Hansenula polymorpha (HepB-HP) were recruited.Standardized questionnaire was used and blood samples were collected 1-6 months (T0) and five years (T1) after the third dose respectively.The titer of anti-HBs was detected by chemiluminescence microparticle imunoassay (CMIA).Those who achieved normal or high antibody response (anti-HBs titer ≥100 mIU/ml) were included in the study and the positive rate (≥ 10 mIU/ml) and titer of anti-HBs at T1 were compared between 5 μg HepB group and 10 μg HepB group.Multivariable analysis was conducted to identify the independent factors associated with the antibody persistence.Results The positive rate of anti-HBs at T1 was 49.92％ (943/1 883) and 75.92％ (1 135/1 495) respectively in 5 μg HepB group and 10 μg HepB group,the difference was significant (x2=237.75,P＜0.001).The anti-IBs geometric mean concentrations at T1 were 10.23 mIU/ml (95％CI:9.38-11.16) and 28.91 mIU/ml (95％CI:26.65-31.35) in the two groups respectively,the difference was also significant (F=280.36,P＜0.001).Among those whose anti-HBs titer was ＜ 10 mIU/ml at T1,the distributions of anti-HBs titer were significantly different between 5 μg HepB group and 10 μg HepB group (x2=39.75,P＜ 0.001).The multivariable analysis showed that dosage of HepB was independently associated with both positive rate and titer of anti-HBs at T1 after excluding the other factors [P＜0.001,OR=1.44(95％ CI:1.20-1.73);P＜0.001,β =0.27 (95％ CI:0.14-0.40)].Conclusion Five year anti-HBs persistence after primary immunization with 10 μg HepB might be better than that after primary immunization with 5 μg HepB among infants who achieved normal or high anti-HBs response after primary HepB immunization.

Comparison of antibody persistence after primary immunization with 5 μg and 10 μg recombinant hepatitis B vaccine among newborns with normal and high response: a five-year following-up / 中华流行病学杂志

Objective To compare the antibody persistence 5 years after primary immunization with 5 μg and 10 μg recombinant hepatitis B vaccine (HepB) among newborns with normal and high response.Methods Newborns who completed three doses of 5 μ g HepB made by recombinant dexyribonucleic acid technique in Saccharomyces (HepB-SC) or 10 μg HepB made by recombinant dexyribonucleic acid technique in Hansenula polymorpha (HepB-HP) were recruited.Standardized questionnaire was used and blood samples were collected 1-6 months (T0) and five years (T1) after the third dose respectively.The titer of anti-HBs was detected by chemiluminescence microparticle imunoassay (CMIA).Those who achieved normal or high antibody response (anti-HBs titer ≥100 mIU/ml) were included in the study and the positive rate (≥ 10 mIU/ml) and titer of anti-HBs at T1 were compared between 5 μg HepB group and 10 μg HepB group.Multivariable analysis was conducted to identify the independent factors associated with the antibody persistence.Results The positive rate of anti-HBs at T1 was 49.92％ (943/1 883) and 75.92％ (1 135/1 495) respectively in 5 μg HepB group and 10 μg HepB group,the difference was significant (x2=237.75,P＜0.001).The anti-IBs geometric mean concentrations at T1 were 10.23 mIU/ml (95％CI:9.38-11.16) and 28.91 mIU/ml (95％CI:26.65-31.35) in the two groups respectively,the difference was also significant (F=280.36,P＜0.001).Among those whose anti-HBs titer was ＜ 10 mIU/ml at T1,the distributions of anti-HBs titer were significantly different between 5 μg HepB group and 10 μg HepB group (x2=39.75,P＜ 0.001).The multivariable analysis showed that dosage of HepB was independently associated with both positive rate and titer of anti-HBs at T1 after excluding the other factors [P＜0.001,OR=1.44(95％ CI:1.20-1.73);P＜0.001,β =0.27 (95％ CI:0.14-0.40)].Conclusion Five year anti-HBs persistence after primary immunization with 10 μg HepB might be better than that after primary immunization with 5 μg HepB among infants who achieved normal or high anti-HBs response after primary HepB immunization.

Immunogenicity and Safety of a DTaP-IPV//PRP~T Vaccine (Pentaxim) Booster Dose During the Second Year of Life in Indian Children Primed with the Same Vaccine.

Objective: To evaluate the immunogenicity and safety of a pentavalent (diphtheria, tetanus, acellular pertussis, inactivated poliovirus, Hib polysaccharide-conjugate) combination vaccine booster dose. Design: Multicenter, open, Phase III clinical study. Setting: Two tertiary-care hospitals in Delhi and Vellore, India. Participants/patients: 207 healthy Indian children. Intervention: The DTaP-IPV//PR~NT vaccine (Pentaxim) was given at 18-19 months of age to children who had been primed with the same vaccine at 6,10,14 weeks of age. Main outcome measures: Immunogenicity was assessed before and 1 month after the booster. Safety was evaluated from parental reports, and investigator assessments. Results: At 18-19 months of age, before boosting, the SP rates against diphtheria, tetanus, poliovirus and PRP were 82.3-100%; 90.0% of participants had anti-PRP ≥0.15 μg/mL. Anti-poliovirus titers were ≥1:8 dilution in 97.9-98.4% of participants. Anti-PT and FHA titers (≥5 EU/mL) were detectable in 82.5% and 90.8% of participants, respectively. One month after the booster dose, SP rates were 99.5% for PRP (≥1.0 μg/mL), 100% for diphtheria, tetanus (≥0.1 IU/mL) and polioviruses (≥8:1/dilution). Seroconversion (4 fold post-booster increase in anti-PT and -FHA concentration) occurred in 96.8% and 91.7%, respectively. Geometric mean concentrations (GMC) increased from 11.7 to 353.1 EU/mL and from 18.2 to 363.4 EU/mL for anti-PT and anti- FHA, respectively. Anti-PRP GMC increased from 1.75 to 70.5 μg/ mL. Vaccine reactogenicity was low; severe solicited reactions were reported by <1.4% of participants. Conclusion: The DTaP-IPV//PRP-T vaccine booster at 18-19 months of age was well tolerated and induced strong antibody responses.