This is a summary, written by members of the CITF Secretariat, of:
Hall VG, Ferreira VH, Ku T, Ierullo M, Majchrzak-Kita B, Chaparro C, Selzner N, Schiff J, McDonald M, Tomlinson G, Kulasingam V, Kumar D, Humar A. Randomized Trial of a Third Dose of mRNA-1273 Vaccine in Transplant Recipients. N Engl J Med, 2021 Aug 11. doi: 10.1056/NEJMc2111462.
The results and/or conclusions contained in the research do not necessarily reflect the views of all CITF members.
Organ transplant recipients often receive immunosuppressant drugs to avoid transplant rejection, but these compounds affect their ability to mount immunity effectively when vaccinated. Indeed, their response after two doses of a COVID-19 vaccine has been shown to be well below that of those who are not immunocompromised. CITF-funded researcher Dr. Deepali Kumar, and collaborators from University Health Network in Toronto, performed the first controlled trial comparing outcomes after receiving a third dose of the Moderna mRNA vaccine versus a saline solution (known as placebo) among organ transplant recipients. In a recent article published in the New England Journal of Medicine, the authors conclude that a third vaccine dose was safe and very effective at increasing antibody levels in organ transplant recipients.
Previous reports indicated that few organ transplant recipients had a detectable antibody response to the standard two-dose COVID-19 vaccination strategy, leaving many potentially still at risk of severe disease. Dr. Kumar and colleagues completed a trial of 120 organ transplant recipients who had previously received two doses of the Moderna vaccine and who did not have a history of a previous COVID-19 infection. The researchers assessed antibody levels, virus neutralization capacity, and T cell responses at one month after a third vaccine dose.
- Antibody levels were above the anti-RBD antibody limits the team had pre-established as suggesting resistance to infection for 55% of the patients that received the third dose of the mRNA vaccine (33/60) versus 18% of patients in the control group (10/57).
- Some patients who received the placebo solution instead of a third dose saw their antibody levels increase – though only modestly in comparison to people who received a third booster dose of the vaccine. This may be due to continued immune activity as a result of the standard two vaccine doses that individuals in the placebo group had previously received.
- The overall neutralization capacity of the samples was significantly higher among individuals who received dose 3 of the vaccine; this capacity remained the same for those in the control group (60% versus 25% positivity).
- SARS-CoV-2-specific T cell counts were greater in the group that received dose 3 than in the control group.
- Only mild side effects were noted after the third vaccine dose. Authors did not observe any incidence of acute organ rejections, an important point to ensure safety of third doses.
The authors conclude that the third dose of the vaccine was well tolerated, and effective at boosting the specific-immune response against the virus. Similar results were observed using the Pfizer–BioNTech vaccine, using a cohort of 101 solid-organ transplant recipients from France.
Authors recommend a booster third dose as a viable option for this population, pending regulatory approval. Because some patients may still remain at risk, public health measures should be maintained, and vaccination of the relatives of these patients should be encouraged.