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

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


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. ( 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.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • 2019-nCoV Vaccine mRNA-1273 / administration & dosage*
  • 2019-nCoV Vaccine mRNA-1273 / adverse effects
  • Aged
  • Antibodies, Neutralizing / blood*
  • COVID-19 / immunology*
  • COVID-19 / prevention & control*
  • COVID-19 / virology
  • Double-Blind Method
  • Female
  • Humans
  • Immunocompromised Host
  • Male
  • Middle Aged
  • Organ Transplantation*
  • SARS-CoV-2*
  • Transplant Recipients*


  • Antibodies, Neutralizing
  • 2019-nCoV Vaccine mRNA-1273

Supplementary concepts

  • SARS-CoV-2 variants

Associated data