Vaccine Research Center, University of Tampere, Tampere, Finland.
Biostatistics, Merck & Co. Inc., Rahway, NJ, USA.
Hum Vaccin Immunother. 2022 Nov 30;18(5):2073747. doi: 10.1080/21645515.2022.2073747. Epub 2022 Jun 2.
Vaccination against hepatitis B (HepB) provides long-term protection against infection. This is despite a reduction in HepB surface antibody (anti-HBs) concentrations over time to levels below the well-accepted correlate of protection of ≥10 mIU/mL. Continued evidence of immune memory and protection despite declined anti-HBs concentrations can be demonstrated by HepB virus surface antigen challenge studies. Long-term immune memory and protection against HepB infection has not been demonstrated previously for the pediatric hexavalent vaccine DTaP5-IPV-HepB-Hib. This phase 3, multicenter, single-group, open-label challenge study (NCT04490499; EudraCT: 2020-000126-26) evaluated immune memory against HepB infection in children who had received DTaP5-IPV-HepB-Hib at 2, 4, and 11-12 months of age, or at 2, 3, 4, and 12 months of age. At age 8-9 years, they were each challenged with 5 μg of monovalent HepB vaccine. Anti-HBs levels were measured on pre-challenge day 1 and post-challenge day 30. At baseline, 45.4% (93 of 205) had anti-HBs levels ≥10 mIU/mL. On post-challenge day 30, 99.5% (201 of 202) had anti-HBs levels ≥10 mIU/mL, regardless of initial vaccination schedule. Post-challenge, geometric mean concentrations increased 71-fold over baseline and 96.0% of children had a ≥4-fold rise in anti-HBs concentrations with similar results across both dosing schedules. The challenge dose was well tolerated. The robust anti-HBs responses after a single 5-μg dose of HepB vaccine confirm the persistence of a HepB immune memory and demonstrate that DTaP5-IPV-HepB-Hib provides long-term protection against HepB.
乙型肝炎(HepB)疫苗接种可提供长期的感染防护。尽管随着时间的推移,乙型肝炎表面抗体(anti-HBs)浓度降至公认的保护相关值≥10 mIU/mL 以下,但仍能提供这种保护。乙型肝炎病毒表面抗原挑战研究证明,尽管 anti-HBs 浓度下降,但仍能持续存在免疫记忆和保护作用。此前,尚未证明儿童六联疫苗 DTaP5-IPV-HepB-Hib 具有长期的免疫记忆和对 HepB 感染的保护作用。这项 3 期、多中心、单组、开放性标签挑战研究(NCT04490499;EudraCT:2020-000126-26)评估了在 2、4 和 11-12 个月龄,或在 2、3、4 和 12 个月龄时接受 DTaP5-IPV-HepB-Hib 接种的儿童对 HepB 感染的免疫记忆。在 8-9 岁时,他们每人接受 5μg 单价 HepB 疫苗接种。在接种前 1 天和接种后 30 天测量 anti-HBs 水平。在基线时,45.4%(205 例中的 93 例)anti-HBs 水平≥10 mIU/mL。在接种后 30 天,无论初始接种方案如何,99.5%(202 例中的 201 例)anti-HBs 水平≥10 mIU/mL。接种后,几何平均浓度比基线增加 71 倍,96.0%的儿童 anti-HBs 浓度升高≥4 倍,两种接种方案的结果相似。该挑战剂量具有良好的耐受性。单次 5μg HepB 疫苗接种后产生的强大 anti-HBs 应答证实了 HepB 免疫记忆的持久性,并表明 DTaP5-IPV-HepB-Hib 可提供长期的 HepB 保护。