mRNA-1273 疫苗两剂和三剂接种后对移植受者中 SARS-CoV-2 变异株的中和作用：一项随机试验的二次分析。

Neutralization of SARS-CoV-2 Variants in Transplant Recipients After Two and Three Doses of mRNA-1273 Vaccine : Secondary Analysis of a Randomized Trial.

机构信息

University Health Network, Toronto, Ontario, Canada (D.K., V.H.F., V.G.H., T.K., M.I., B.M., G.T., A.H.).

Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Sinai Health, Toronto, Ontario, Canada (Q.H.).

出版信息

Ann Intern Med. 2022 Feb;175(2):226-233. doi: 10.7326/M21-3480. Epub 2021 Nov 23.

DOI:10.7326/M21-3480

PMID:34807716

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8628360/

Abstract

BACKGROUND

COVID-19 is more severe in transplant recipients. Variants of concern have supplanted wild-type virus. In transplant recipients, data are limited on 2-dose or 3-dose vaccine immunogenicity against variant viruses.

OBJECTIVE

To assess neutralizing antibody responses against SARS-CoV-2 variants in transplant recipients after 2 and 3 vaccine doses.

DESIGN

Secondary analysis of a randomized, double-blind, controlled trial of a third dose of mRNA-1273 vaccine versus placebo. (ClinicalTrials.gov: NCT04885907).

SETTING

Single-center transplant program.

PATIENTS

Organ transplant recipients.

INTERVENTION

Third dose of mRNA-1273 vaccine versus placebo.

MEASUREMENTS

Sera were analyzed for neutralization against wild-type virus and the Alpha, Beta, and Delta variants using a surrogate virus neutralization assay and a spike-pseudotyped lentivirus assay.

RESULTS

A total of 117 transplant recipients were analyzed (60 in the mRNA-1273 group and 57 in the placebo group). Sera were obtained before and 4 to 6 weeks after the third dose. After 2 doses, the proportion of patients with positive neutralization for all 3 variants was small compared with wild-type virus. After the third dose of mRNA-1273 vaccine, the proportion with a positive neutralization response versus placebo was improved for all 3 variants as measured by both assays. Based on the pseudovirus neutralization assay against the Delta variant, 33 of 60 (55%) patients were positive in the mRNA-1273 group versus 10 of 57 (18%) in the placebo group (difference, 37 [95% CI, 19 to 53] percentage points). The differences were 36 (CI, 17 to 51) percentage points for the Alpha variant and 31 (CI, 15 to 46) percentage points for the Beta variant. In the mRNA-1273 group, lower neutralization values were observed for variants compared with wild-type virus, especially the Beta variant.

LIMITATIONS

There is no clear correlate of protection for neutralizing antibody. This was a secondary analysis.

CONCLUSION

In organ transplant recipients, a third dose of mRNA vaccine increases neutralizing antibody response against SARS-CoV-2 variants compared with placebo.

PRIMARY FUNDING SOURCE

Ajmera Transplant Centre.

摘要

背景

COVID-19 在移植受者中更为严重。关注变体已经取代了野生型病毒。在移植受者中，关于针对变体病毒的 2 剂或 3 剂疫苗免疫原性的数据有限。

目的

评估 2 剂和 3 剂 mRNA-1273 疫苗接种后针对 SARS-CoV-2 变体的中和抗体反应。

设计

对第三剂 mRNA-1273 疫苗与安慰剂的随机、双盲、对照试验的二次分析。（ClinicalTrials.gov：NCT04885907）。

地点

单中心移植计划。

患者

器官移植受者。

干预措施

第三剂 mRNA-1273 疫苗与安慰剂。

测量

使用替代病毒中和测定法和 Spike 假型慢病毒测定法分析血清对野生型病毒以及 Alpha、Beta 和 Delta 变体的中和作用。

结果

共分析了 117 名移植受者（mRNA-1273 组 60 例，安慰剂组 57 例）。在第三剂后 4 至 6 周采集了血清。与野生型病毒相比，在接受 2 剂后，所有 3 种变体具有阳性中和作用的患者比例较小。在接受 mRNA-1273 疫苗第三剂后，与安慰剂相比，两种检测方法均显示所有 3 种变体的阳性中和反应比例均有所提高。根据针对 Delta 变体的假病毒中和测定法，在 mRNA-1273 组中有 33 例（60%）患者为阳性，而在安慰剂组中有 10 例（57%）为阳性（差异为 37 [95%CI，19 至 53]个百分点）。对于 Alpha 变体，差异为 36（CI，17 至 51）个百分点，对于 Beta 变体，差异为 31（CI，15 至 46）个百分点。在 mRNA-1273 组中，与野生型病毒相比，变体的中和值较低，尤其是 Beta 变体。