SENIEUR方案以及按年龄、性别和疫苗接种途径划分的健康老年人中乙型肝炎疫苗接种的效果。
The SENIEUR protocol and the efficacy of hepatitis B vaccination in healthy elderly persons by age, gender, and vaccine route.
作者信息
Edelman Robert, Deming Meagan E, Toapanta Franklin R, Heuser Mark D, Chrisley Lisa, Barnes Robin S, Wasserman Steven S, Blackwelder William C, Handwerger Barry S, Pasetti Marcela, Siddiqui Khan M, Sztein Marcelo B
机构信息
1Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, USA.
2Department of Medicine, University of Maryland School of Medicine, Baltimore, USA.
出版信息
Immun Ageing. 2020 Apr 28;17:9. doi: 10.1186/s12979-020-00179-9. eCollection 2020.
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%, = 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.
背景
对乙型肝炎疫苗的反应降低与衰老、混杂因素和合并症以及意外皮下接种有关。我们假设，老年成年人对肌内注射（IM）疫苗的抗体和T细胞介导的免疫反应（T-CMI）在注入皮下脂肪时会减弱，与混杂因素无关。
结果
52名健康的社区居住老年成年人（65 - 82岁），乙肝血清学阴性，按照SENIEUR方案纳入，作为严格健康的人群。这些老年人被随机分为皮下或肌内接种许可的明矾佐剂重组乙肝疫苗，接种部位通过成像验证。以乙肝表面抗体（HBsAb）≥10 IU/L定义的应答率，老年人显著低于一组12名健康的21 - 34岁年轻志愿者。此外，接受肌内注射疫苗的老年参与者比接受皮下注射的更有可能产生应答（54%对16%，P = 0.008）。肌内注射组的低血清转化率随年龄增长逐渐下降，应答者的HBsAb滴度显著较低且同种型反应有限。此外，老年人中Th1和Th2亚群的应答者百分比和应答强度方面的T-CMI（增殖和细胞因子产生）均显著降低。
结论
我们的数据表明，通过峰值滴度和应答率衡量，皮下接种的免疫原性减弱。此外，与年轻人群相比，即使在严格健康且肌内注射部位经确认的老年人群中，对初次明矾佐剂蛋白抗原的B细胞和T细胞介导的免疫反应在质量和数量上的缺陷仍然存在。
临床试验注册
ClinicalTrials.gov，NCT04162223。2019年11月14日注册。回顾性注册。
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