Further data back COVID booster shot in transplant patients

Antibody response against SARS-CoV-2 was significantly enhanced with a third dose of mRNA-1273 vaccine in organ transplant recipients, reveal data of a randomized trial.

“In organ-transplant recipients, the standard two-dose vaccination strategy for COVID-19 has suboptimal immunogenicity ... because the immunosuppressive therapy that prevents graft rejection may decrease the immune response to vaccines,” experts explained.

At 4-month follow-up, the primary outcome of a serologic response — defined as an anti–receptor-binding domain (RBD) antibody level of ≥100 U/mL — was achieved in significantly more patients who received the third dose of vaccine compared with the placebo group (55 percent vs 18 percent; p<0.001). [N Engl J Med 2021;doi:10.1056/NEJMc2111462]

The percentage of virus neutralization after the third dose was also substantially higher in the vaccine arm vs the placebo arm (median, 71 percent vs 13 percent, 95 percent confidence interval [CI], 11 to 76 percentage points).

Of note, the increase in anti-RBD antibody level was 75 times greater after the third vaccine dose compared with the placebo group. 

In addition, SARS-CoV-2–specific T-cell counts were also greater after the third vaccine dose compared with that seen in the placebo group (432 vs 67 cells per 106 CD4+ T cells; 95 percent CI, 46–986).

“Together, these results provide convincing evidence of enhanced vaccine efficacy in transplant recipients, for whom great concern has been raised about a weak or even negligible immune response after the standard two doses of mRNA vaccine,” wrote Drs Winfred Williams and Julie Ingelfinger from Massachusetts General Hospital in Boston, Massachusetts, US, in a linked editorial. [N Engl J Med 2021;doi:10.1056/NEJMe2112866]

In the double-blind study, 120 organ-transplant recipients (median age 66.6 years) who had two doses of mRNA-1273 vaccine were randomized 1:1 to receive a third dose of mRNA-1273 vaccine or saline placebo, given 2 months after the second vaccine dose.

Although local and systemic adverse events were slightly more common with mRNA-1273 than placebo, these were mild and none were of grade 3 or 4 events or hospitalized.

“In addition, no cases of organ rejection — something that is of great concern to transplant recipients — were reported after the booster dose. Overall, at this juncture, the benefit of third-dose vaccination, at least with the mRNA-1273 vaccine, appears to outweigh the risks,” noted Williams and Ingelfinger.

“We conclude that a third-dose booster COVID-19 vaccine should be considered, in conjunction with regulatory approval, for transplant recipients who have received two doses of mRNA-1273,” urged the researchers.

The US FDA and CDC have recently authorized the use of booster COVID-19 mRNA-based vaccines for certain immunocompromised patients.

As the follow-up duration in the current randomized trial was short, longer-term data would be needed to provide more clarity.

“Although antibody levels increased impressively after the third dose of mRNA-1273, trial follow-up was short-term. Continued monitoring of the participants in this trial and of those in prospective nonrandomized studies will be important,” Williams and Ingelfinger stated.