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初免-加强、双倍剂量流感疫苗对慢性阻塞性肺疾病的免疫作用:一项试点观察性研究

Prime-boost, double-dose influenza vaccine immunity in COPD: a pilot observational study.

作者信息

Anderson Gary P, Irving Louis B, Jarnicki Andrew, Kedzierska Katherine, Koutsakos Marios, Kent Stephen, Hurt Aeron C, Wheatley Adam K, Nguyen Thi H O, Snape Natale, Upham John W

机构信息

Lung Health Research Centre, Department of Biochemistry and Pharmacology, The University of Melbourne, Parkville, Australia.

Department of Respiratory Medicine, The Royal Melbourne Hospital, Parkville, Australia.

出版信息

ERJ Open Res. 2023 Mar 6;9(2). doi: 10.1183/23120541.00641-2021. eCollection 2023 Mar.

Abstract

BACKGROUND

COPD patients are more susceptible to viral respiratory infections and their sequelae, and have intrinsically weaker immune responses to vaccinations against influenza and other pathogens. Prime-boost, double-dose immunisation has been suggested as a general strategy to overcome weak humoral response to vaccines, such as seasonal influenza vaccination, in susceptible populations with weak immunity. However, this strategy, which may also provide fundamental insights into the nature of weakened immunity, has not been formally studied in COPD.

METHODS

We conducted an open-label study of seasonal influenza vaccination in 33 vaccine-experienced COPD patients recruited from established cohorts (mean age 70 (95% CI 66.9-73.2) years; mean forced expiratory volume in 1 s/forced vital capacity ratio 53.4% (95% CI 48.0-58.8%)). Patients received two sequential standard doses of the 2018 quadrivalent influenza vaccine (15 μg haemagglutinin per strain) in a prime-boost schedule 28 days apart. We measured strain-specific antibody titres, an accepted surrogate of likely efficacy, and induction of strain-specific B-cell responses following the prime and boost immunisations.

RESULTS

Whereas priming immunisation induced the expected increase in strain-specific antibody titres, a second booster dose was strikingly ineffective at further increasing antibody titres. Similarly, priming immunisation induced strain-specific B-cells, but a second booster dose did not further enhance the B-cell response. Poor antibody responses were associated with male gender and cumulative cigarette exposure.

CONCLUSIONS

Prime-boost, double-dose immunisation does not further improve influenza vaccine immunogenicity in previously vaccinated COPD patients. These findings underscore the need to design more effective vaccine strategies for COPD patients for influenza.

摘要

背景

慢性阻塞性肺疾病(COPD)患者更容易发生病毒性呼吸道感染及其后遗症,并且对流感和其他病原体疫苗的免疫反应本质上较弱。对于免疫力较弱的易感人群,如季节性流感疫苗接种,初免-加强、双剂量免疫已被提议作为克服对疫苗的弱体液反应的一般策略。然而,这种策略,也可能为免疫减弱的本质提供基本见解,尚未在COPD中进行正式研究。

方法

我们对从已建立队列中招募的33名有疫苗接种史的COPD患者进行了一项季节性流感疫苗接种的开放标签研究(平均年龄70(95%CI 66.9-73.2)岁;平均第1秒用力呼气容积/用力肺活量比值53.4%(95%CI 48.0-58.8%))。患者按照初免-加强方案,在间隔28天的时间内接受两剂连续的2018年四价流感疫苗标准剂量(每株15μg血凝素)。我们测量了株特异性抗体滴度,这是一个公认的可能疗效替代指标,以及初免和加强免疫后株特异性B细胞反应的诱导情况。

结果

虽然初免诱导了株特异性抗体滴度的预期增加,但第二剂加强剂量在进一步增加抗体滴度方面明显无效。同样,初免诱导了株特异性B细胞,但第二剂加强剂量并未进一步增强B细胞反应。抗体反应不佳与男性性别和累积吸烟暴露有关。

结论

初免-加强、双剂量免疫并不能进一步提高先前接种过疫苗的COPD患者的流感疫苗免疫原性。这些发现强调了为COPD患者设计更有效的流感疫苗策略的必要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa60/9986756/d846372b9f9a/00641-2021.01.jpg

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