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For organ transplant recipients, a third dose of Moderna's COVID-19 vaccine more than tripled the proportion with a sufficient antibody response, a randomized trial showed.

A third dose 2 months after the regular two-shot series produced a serologic response previously shown to confer at least 50% virus neutralization (an anti-receptor-binding domain [RBD] antibody level ≥100 U/mL) at month 4 in 55% of patients compared with 18% in the placebo group (33 of 60 patients vs 10 of 57, P<0.001).

The had short follow-up and was not powered to determine clinical impact on infection rate or other outcomes, cautioned Atul Humar, MD, of the University Health Network in Toronto, and colleagues in their research letter published in the (NEJM). A single patient in the placebo group developed COVID-19 during the trial.

However, the extra dose was "safe when risk versus benefit was considered," they noted, concluding 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."

The findings were in line with recent observational studies.

Local and systemic adverse events were "slightly" more common with the third dose, as might be expected, but none were serious. Importantly, there were no signals of acute rejection of the transplanted organ.

In an , NEJM deputy editors Winfred Williams, MD, and Julie Ingelfinger, MD, called the findings convincing and agreed that the third dose appears warranted in transplant patients, at least with Moderna's vaccine.

Weak or even no immune response after the standard two doses of mRNA vaccine has been reported in this group, leading to the proposal of a third dose, which has been supported by an anecdotal report and observational studies. FDA is reportedly weighing regulatory avenues for booster shots in immunocompromised patients.

Some older and earlier-vaccinated individuals have also been considering booster shots. However, the against antibody testing to determine immunity after vaccination.

Just how far to extrapolate the results of Humar's trial isn't clear, Williams and Ingelfinger noted.

"Although some may infer from these data that solid-organ transplant recipients should routinely receive a third vaccine dose, additional randomized trials will be key to learning how to better care for solid-organ transplant recipients during this pandemic," they argued.

One concern was the short-term follow-up of only 4 months, with the editorialists calling for continued monitoring of the antibody response over time.

Another was the modest size: 120 COVID-19-naive solid-organ transplant recipients who were randomized at a median 3.16 years post-transplantation to a third dose of mRNA-1273 (Moderna) vaccine or a saline placebo 2 months after the second dose.

The editorialists also highlighted some imbalances between groups in the type of transplant, with fewer lung transplants and more abdominal organ transplants in the vaccine group than in the placebo group. Time from transplantation was also a median of 1.37 years shorter in the placebo group.

However, baseline immunosuppression levels and medication types and doses were similar between groups, as were the lymphocyte counts.

Secondary measures of immunogenicity also favored the booster shot:

• Change in anti-RBD antibody level from before to after the third dose (75 times greater)
• Median percent virus neutralization (71% vs 13%)
• Proportion above the 30% threshold for neutralizing antibody positivity (60% vs 25%)
• Median severe SARS-CoV-2-specific T-cell counts (432 vs 67 cells per 10⁶ CD4+ T cells)

The researchers noted that a small number of the placebo group patients had modest increases in antibody levels. "This may reflect ongoing mRNA vaccine-induced B-cell stimulation, as recently described, and highlights the importance of evaluating a control group," they wrote.

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