Background

Patients with chronic renal insufficiency on maintenance haemodialysis face an increased risk of COVID-19 induced mortality and impaired vaccine responses. To date, only a few studies have addressed SARS-CoV-2 vaccine elicited immunity in this immunocompromised population.

Methods

We assessed immunogenicity of the mRNA vaccine BNT162b2 in at-risk dialysis patients and characterised systemic cellular and humoral immune responses in serum and saliva using interferon γ release assay and multiplex-based cytokine and immunoglobulin measurements. We further compared binding capacity and neutralization efficacy of vaccination-induced immunoglobulins against emerging SARS-CoV-2 variants Alpha, Beta, Epsilon and Cluster 5 by ACE2-RBD competition assay.

Findings

Patients on maintenance haemodialysis exhibit detectable but variable cellular and humoral immune responses against SARS-CoV-2 and variants of concern after a two-dose regimen of BNT162b2. Although vaccination-induced immunoglobulins were detectable in saliva and plasma, both anti-SARS-CoV-2 IgG and neutralization efficacy was reduced compared to a vaccinated non-dialysed control population. Similarly, T-cell mediated interferon γ release after stimulation with SARS-CoV-2 spike peptides was significantly diminished.

Interpretation

Quantifiable humoral and cellular immune responses after BNT162b2 vaccination in individuals on maintenance haemodialysis are encouraging, but urge for longitudinal follow-up to assess longevity of immunity. Diminished virus neutralization and interferon γ responses in the face of emerging variants of concern may favour this at-risk population for re-vaccination using modified vaccines at the earliest opportunity.

Funding

Initiative and Networking Fund of the Helmholtz Association of German Research Centres, EU Horizon 2020 research and innovation program, State Ministry of Baden-Württemberg for Economic Affairs, Labour and Tourism.

中文翻译：

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血液透析患者中​​ SARS-CoV-2 mRNA 疫苗的细胞和体液免疫原性

 背景

接受维持性血液透析的慢性肾功能不全患者面临着因 COVID-19 导致的死亡和疫苗反应受损的风险增加。迄今为止，只有少数研究涉及 SARS-CoV-2 疫苗在免疫功能低下人群中引发免疫力的问题。

 方法

我们评估了 mRNA 疫苗 BNT162b2 在高危透析患者中​​的免疫原性，并使用干扰素 γ 释放测定和基于多重的细胞因子和免疫球蛋白测量来表征血清和唾液中的全身细胞和体液免疫反应。我们通过 ACE2-RBD 竞争测定进一步比较了疫苗接种诱导的免疫球蛋白对新兴 SARS-CoV-2 变体 Alpha、Beta、Epsilon 和 Cluster 5 的结合能力和中和功效。

 发现

接受维持性血液透析的患者在接受两剂 BNT162b2 治疗后，表现出针对 SARS-CoV-2 和相关变体的可检测但可变的细胞和体液免疫反应。尽管在唾液和血浆中可检测到疫苗接种诱导的免疫球蛋白，但与接种疫苗的非透析对照人群相比，抗 SARS-CoV-2 IgG 和中和功效均降低。同样，用 SARS-CoV-2 刺突肽刺激后，T 细胞介导的干扰素 γ 释放显着减少。

 解释

维持性血液透析个体接种 BNT162b2 疫苗后可量化的体液和细胞免疫反应令人鼓舞，但迫切需要进行纵向随访以评估免疫寿命。面对新出现的令人担忧的变种，病毒中和和干扰素γ反应减弱可能有利于这些高危人群尽早使用改良疫苗重新接种疫苗。

 资金

德国亥姆霍兹研究中心协会倡议和网络基金、欧盟地平线 2020 研究和创新计划、巴登-符腾堡州经济事务、劳工和旅游部。