Background Reduced response to hepatitis B vaccines is associated with aging, confounding and comorbid conditions, as well as inadvertent subcutaneous (SC) inoculation. We hypothesized that the antibody and T cell-mediated immune responses (T-CMI) of elderly adults to a vaccine intended for intramuscular (IM) administration would be attenuated when deposited into SC fat, independent of confounding conditions. Results Fifty-two healthy, community dwelling elderly adults (65-82 years), seronegative for HBV, were enrolled in the SENIEUR protocol as a strictly healthy population. These seniors were randomized to receive a licensed alum-adjuvanted recombinant HBV vaccine either SC or IM, with the inoculum site verified by imaging. The response rates, defined as hepatitis B surface antibodies (HBsAb) ≥10 IU/L, were significantly lower in the elderly than in young adults, a group of 12, healthy, 21-34-year-old volunteers. Moreover, elderly participants who received the vaccine IM were significantly more likely to be responders than those immunized SC (54% versus 16%, p = 0.008). The low seroconversion rate in the IM group progressively declined with increasing age, and responders had significantly lower HBsAb titers and limited isotype responses. Moreover, T-CMI (proliferation and cytokine production) were significantly reduced in both percentage of responders and intensity of the response for both Th1 and Th2 subsets in the elderly. Conclusions Our data demonstrate the blunted immunogenicity of SC inoculation as measured by peak titers and response rates. Further, the qualitative and quantitative deficits in B- and T-CMI responses to primary alum adjuvanted protein antigens persisted even in strictly healthy elderly populations with verified IM placement compared to younger populations. Clinical trial registration ClinicalTrials.gov, NCT04162223. Registered 14 November 2019. Retrospectively registered.

中文翻译：

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SENIEUR 方案以及按年龄、性别和疫苗途径划分的健康老年人乙型肝炎疫苗接种的效果。


背景 对乙型肝炎疫苗的反应降低与衰老、混杂和合并症以及无意的皮下 (SC) 接种有关。我们假设，老年人对肌肉注射（IM）疫苗的抗体和 T 细胞介导的免疫反应（T-CMI）在沉积到 SC 脂肪中时会减弱，与混杂条件无关。结果 52 名健康、社区居住的老年人（65-82 岁）乙肝血清阴性，作为严格健康人群纳入 SENIEUR 方案。这些老年人被随机分配接受经许可的明矾佐剂重组乙型肝炎疫苗皮下注射或肌内注射，并通过成像验证接种部位。老年人的缓解率（定义为乙型肝炎表面抗体 (HBsAb) ≥10 IU/L）显着低于年轻人（由 12 名健康的 21-34 岁志愿者组成）。此外，接受 IM 疫苗接种的老年参与者比 SC 接种疫苗的老年参与者更有可能产生反应（54% 比 16%，p = 0.008）。 IM 组的低血清转化率随着年龄的增长而逐渐下降，应答者的 HBsAb 滴度显着降低，同种型应答也有限。此外，老年人中 Th1 和 Th2 亚群的 T-CMI（增殖和细胞因子产生）的应答者百分比和应答强度均显着降低。结论 我们的数据证明了通过峰值滴度和反应率测量的 SC 接种的免疫原性减弱。 此外，与年轻人群相比，即使在经过验证的 IM 放置的严格健康的老年人群中，B 和 T-CMI 对初级明矾佐剂蛋白抗原的反应的定性和定量缺陷仍然存在。临床试验注册ClinicalTrials.gov，NCT04162223。 2019 年 11 月 14 日注册。追溯注册。