Effect of Immunosuppression on the Immunogenicity of mRNA Vaccines to SARS-CoV-2,Annals of Internal Medicine

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Effect of Immunosuppression on the Immunogenicity of mRNA Vaccines to SARS-CoV-2
Annals of Internal Medicine ( IF 39.2 ) Pub Date : 2021-08-31 , DOI: 10.7326/m21-1757
Parakkal Deepak ₁ , Wooseob Kim ₁ , Michael A Paley ₁ , Monica Yang ₂ , Alexander B Carvidi ₂ , Emanuel G Demissie ₂ , Alia A El-Qunni ₁ , Alem Haile ₁ , Katherine Huang ₁ , Baylee Kinnett ₁ , Mariel J Liebeskind ₁ , Zhuoming Liu ₁ , Lily E McMorrow ₁ , Diana Paez ₂ , Niti Pawar ₂ , Dana C Perantie ₁ , Rebecca E Schriefer ₁ , Shannon E Sides ₁ , Mahima Thapa ₁ , Maté Gergely ₁ , Suha Abushamma ₁ , Sewuese Akuse ₁ , Michael Klebert ₁ , Lynne Mitchell ₁ , Darren Nix ₁ , Jonathan Graf ₂ , Kimberly E Taylor ₂ , Salim Chahin ₁ , Matthew A Ciorba ₁ , Patricia Katz ₂ , Mehrdad Matloubian ₂ , Jane A O'Halloran ₁ , Rachel M Presti ₁ , Gregory F Wu ₁ , Sean P J Whelan ₁ , William J Buchser ₁ , Lianne S Gensler ₃ , Mary C Nakamura ₃ , Ali H Ellebedy ₁ , Alfred H J Kim ₁

Affiliation

Abstract

Background:

Patients with chronic inflammatory disease (CID) treated with immunosuppressive medications have increased risk for severe COVID-19. Although mRNA-based SARS-CoV-2 vaccination provides protection in immunocompetent persons, immunogenicity in immunosuppressed patients with CID is unclear.

Objective:

To determine the immunogenicity of mRNA-based SARS-CoV-2 vaccines in patients with CID.

Design:

Prospective observational cohort study.

Setting:

Two U.S. CID referral centers.

Participants:

Volunteer sample of adults with confirmed CID eligible for early COVID-19 vaccination, including hospital employees of any age and patients older than 65 years. Immunocompetent participants were recruited separately from hospital employees. All participants received 2 doses of mRNA vaccine against SARS-CoV-2 between 10 December 2020 and 20 March 2021. Participants were assessed within 2 weeks before vaccination and 20 days after final vaccination.

Measurements:

Anti–SARS-CoV-2 spike (S) IgG⁺ binding in all participants, and neutralizing antibody titers and circulating S-specific plasmablasts in a subset to assess humoral response after vaccination.

Results:

Most of the 133 participants with CID (88.7%) and all 53 immunocompetent participants developed antibodies in response to mRNA-based SARS-CoV-2 vaccination, although some with CID developed numerically lower titers of anti-S IgG. Anti-S IgG antibody titers after vaccination were lower in participants with CID receiving glucocorticoids (n = 17) than in those not receiving them; the geometric mean of anti-S IgG antibodies was 357 (95% CI, 96 to 1324) for participants receiving prednisone versus 2190 (CI, 1598 to 3002) for those not receiving it. Anti-S IgG antibody titers were also lower in those receiving B-cell depletion therapy (BCDT) (n = 10). Measures of immunogenicity differed numerically between those who were and those who were not receiving antimetabolites (n = 48), tumor necrosis factor inhibitors (n = 39), and Janus kinase inhibitors (n = 11); however, 95% CIs were wide and overlapped. Neutralization titers seemed generally consistent with anti-S IgG results. Results were not adjusted for differences in baseline clinical factors, including other immunosuppressant therapies.

Limitations:

Small sample that lacked demographic diversity, and residual confounding.

Conclusion:

Compared with nonusers, patients with CID treated with glucocorticoids and BCDT seem to have lower SARS-CoV-2 vaccine-induced antibody responses. These preliminary findings require confirmation in a larger study.

Primary Funding Source:

The Leona M. and Harry B. Helmsley Charitable Trust, Marcus Program in Precision Medicine Innovation, National Center for Advancing Translational Sciences, and National Institute of Arthritis and Musculoskeletal and Skin Diseases.

中文翻译：

免疫抑制对 SARS-CoV-2 mRNA 疫苗免疫原性的影响

**视觉摘要。免疫抑制对 mRNA SARS-CoV-2 疫苗免疫原性的影响。**
有证据表明，免疫抑制患者对基于 mRNA 的 SARS-CoV-2 疫苗接种的免疫原性可能会降低。这项研究评估了 133 名患有潜在慢性炎性疾病的参与者对 2 剂基于 mRNA 的 SARS-CoV-2 疫苗的反应，其中许多人正在接受糖皮质激素、B 细胞耗竭疗法或其他免疫抑制剂疗法。

抽象的

背景：

接受免疫抑制药物治疗的慢性炎症性疾病 (CID) 患者患严重 COVID-19 的风险增加。尽管基于 mRNA 的 SARS-CoV-2 疫苗接种可为免疫功能正常的人提供保护，但免疫抑制 CID 患者的免疫原性尚不清楚。

客观的：

确定基于 mRNA 的 SARS-CoV-2 疫苗对 CID 患者的免疫原性。

设计：

前瞻性观察性队列研究。

环境：

两个美国 CID 转诊中心。

参与者：

符合早期 COVID-19 疫苗接种条件的确诊 CID 成人志愿者样本，包括任何年龄的医院员工和 65 岁以上的患者。免疫能力强的参与者与医院员工分开招募。在 2020 年 12 月 10 日至 2021 年 3 月 20 日期间，所有参与者都接受了 2 剂针对 SARS-CoV-2 的 mRNA 疫苗。参与者在接种疫苗前 2 周和最终接种疫苗后 20 天内接受了评估。

测量：

所有参与者的抗 SARS-CoV-2 刺突 (S) IgG ⁺结合，中和抗体滴度和一个子集中的循环 S 特异性浆母细胞，以评估疫苗接种后的体液反应。

结果：

133 名 CID 参与者中的大多数 (88.7%) 和所有 53 名免疫能力强的参与者针对基于 mRNA 的 SARS-CoV-2 疫苗接种产生了抗体，尽管一些 CID 患者的抗 S IgG 滴度在数值上较低。接受糖皮质激素的 CID 参与者 ( n = 17)接种后抗 S IgG 抗体滴度低于未接受糖皮质激素的参与者；接受泼尼松的参与者的抗 S IgG 抗体几何平均值为 357（95% CI，96 至 1324），而未接受泼尼松的参与者的几何平均值为 2190（CI，1598 至 3002）。接受 B 细胞耗竭疗法 (BCDT) ( n = 10)的患者的抗 S IgG 抗体滴度也较低。接受和未接受抗代谢物的人之间的免疫原性测量在数值上存在差异（n = 48)、肿瘤坏死因子抑制剂 ( n = 39) 和 Janus 激酶抑制剂 ( n = 11)；然而，95% 的 CI 很宽且重叠。中和效价似乎与抗 S IgG 结果大体一致。结果未针对基线临床因素的差异进行调整，包括其他免疫抑制剂治疗。