In organ transplant recipients, the standard two-dose vaccination strategy for coronavirus disease 2019 has suboptimal immunogenicity. It has been asked if a third booster dose in transplant patients may be safe and augment the immune response. 

METHODS: A double-blind, randomized, controlled trial of a third dose of mRNA-1273 vaccine compared with placebo. The transplant recipients who received two doses of mRNA-1273 were randomly assigned in a 1:1 ratio to receive either a third dose of the mRNA-1273 vaccine or a saline placebo 2 months following the second dose of the vaccine (0, 1, and 3 months). The primary outcome was a serologic response featured by an anti-receptor-binding domain antibody level of at least 100 U per milliliter at 4 months. 

RESULTS: 120 organ-transplant recipients were enrolled, and no patient had a previous diagnosis of COVID-19. At month 4, an anti-RBD antibody level of at least 100 U per milliliter was found in 33 of 60 patients (55%) in the mRNA-1273 group and 10 of 57 patients (18%) in the placebo group. After the third dose, the median percent virus neutralization was 71% in the mRNA1273 group, and 13% in the placebo group (95% CI for the between-group difference, 11 to 76 percentage points), and the percentage of patients above the 30% threshold for neutralizing antibody positivity was 60% and 25%, respectively. 

CONCLUSIONS: The third dose of mRNA vaccine in transplant recipients had substantially higher immunogenicity compared to placebo, as seen in the analysis of both primary and secondary trial endpoints. Besides, a third dose was safe when risk versus benefit was considered. In addition, a modest increase in antibody levels showed the importance of ongoing mRNA vaccine-induced B-cell stimulation. The authors concluded that a third-dose booster COVID 19 vaccine should be considered, following regulatory approvals, for transplant recipients who have received two doses of mRNA-1273. 

Reference: Hall VG, Ferreira VH, Ku T, Ierullo M, et al. Rnaodmized trial of a third dose of mRNA-1273 vaccine in transplant recipients. NEJM. 2021; DOI: 10.1056/NEJMc2111462