血液透析患者中 SARS-CoV-2 mRNA 疫苗的细胞和体液免疫原性。
Cellular and humoral immunogenicity of a SARS-CoV-2 mRNA vaccine in patients on haemodialysis.
机构信息
Helmholtz Centre for Infection Research, Braunschweig, Germany; TWINCORE GmbH, Centre for Experimental and Clinical Infection Research, a joint venture of the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Germany.
NMI Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, Germany.
出版信息
EBioMedicine. 2021 Aug;70:103524. doi: 10.1016/j.ebiom.2021.103524. Epub 2021 Aug 12.
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.
背景
接受维持性血液透析的慢性肾功能不全患者面临 COVID-19 感染导致死亡率增加和疫苗应答受损的风险。迄今为止,只有少数研究探讨了这种免疫功能低下人群中 SARS-CoV-2 疫苗引发的免疫。
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释放试验和基于多重的细胞因子和免疫球蛋白测量法,在血清和唾液中评估了系统细胞和体液免疫应答。我们进一步通过 ACE2-RBD 竞争测定比较了接种诱导的免疫球蛋白对新兴的 SARS-CoV-2 变体 Alpha、Beta、Epsilon 和 Cluster 5 的结合能力和中和效力。
结果
接受维持性血液透析的患者在接受 BNT162b2 两剂方案后,针对 SARS-CoV-2 和关注变体可检测到但可变的细胞和体液免疫应答。尽管在唾液和血浆中可检测到接种诱导的免疫球蛋白,但与接种的非透析对照人群相比,抗 SARS-CoV-2 IgG 和中和效力均降低。同样,用 SARS-CoV-2 刺突肽刺激后 T 细胞介导的干扰素γ释放显著减少。
解释
接受维持性血液透析的个体在 BNT162b2 接种后可检测到可量化的体液和细胞免疫应答,令人鼓舞,但需要进行纵向随访以评估免疫持久性。在出现关注的新兴变体的情况下,病毒中和和干扰素γ反应降低,这可能使这一高危人群在最早的机会时使用改良疫苗进行再接种。
资助
德国亥姆霍兹协会研究中心倡议和网络基金、欧盟地平线 2020 研究和创新计划、巴登-符腾堡州州政府经济事务、劳动和旅游部。