This is a summary, written by members of the CITF Secretariat, of:

Hall VG, Ferreira VH, Ierullo M, Ku T, Marinelli T, Majchrzak-Kita B, Yousuf A, Kulasingam V, Humar A, Kumar D. Humoral and Cellular immune response and Safety of 2-dose SARS-CoV-2 mRNA-1273 (Moderna) vaccine in Solid Organ Transplant Recipients. Am J Transplant. 2021 August 00:1-10 doi: 10.1111/ajt.16766

The results and/or conclusions contained in the research do not necessarily reflect the views of all CITF members.

Antibody levels, cell-mediated immunity, and safety were evaluated in solid organ transplant recipients who received two doses of the Moderna vaccine. Key findings from this study are as follows: 65.5% of patients had no detectable antibody (anti-RBD) response following the second vaccine dose; 73.1% were not able to neutralize the virus after the second dose; nevertheless, in a sub-study, nearly half of patients with no detectable anti-RBD demonstrated a strong T-cell response. This CITF/VSRG-funded study is led by Dr. Deepali Kumar at the University Health Network, who continues to evaluate the immunogenicity and safety of COVID-19 vaccines in transplant recipients across Canada. 

Because they are immunosuppressed, solid organ transplant recipients have been shown to be at increased risk of contracting severe COVID-19 and to have reduced COVID-19 vaccine efficacy. It is therefore important to closely monitor whether COVID-19 vaccination protects this vulnerable population against disease.

Key points:

  • 6/121 (5.0%) of transplant recipients demonstrated a positive anti-RBD response after the first dose of the vaccine and 38/110 (34.5%) after the second dose, leaving 72/110 (65.5%) with no detectable anti-RBD
  • 7/119 (5.9%) of patients had antibody neutralization capacity after the first dose of the vaccine, while 29/108 (26.9%) after the second dose, leaving 79/108 (73.1%) with no detectable neutralization capacity
  • In a subset of participants, 4/40 (10%) had a positive T-cell response after the first dose, which increased to 23/48 (47.9%) after the second dose
  • The Moderna vaccine was safe and well-tolerated among participants

In an article recently published in the American Journal of Transplantation, CITF- and VSRG-funded researcher, Dr. Deepali Kumar from the University Health Network in Toronto as well as colleagues, report on the immunogenicity and safety profile of the Moderna COVID-19 vaccine in individuals who have received an organ transplant. In total, 127 participants were enrolled in the study and were followed through their two-dose regimen of the Moderna mRNA vaccine, with a 28-day interval between doses. Blood was collected at three timepoints: (1) before the first dose, (2) four weeks after the first dose, and (3) 4-6 weeks after the second dose. Participants were also monitored for safety and adverse events following vaccination throughout the study period.

Immunogenicity of the vaccine was evaluated by measuring antibody levels against the SARS-CoV-2 spike protein receptor binding domain (anti-RBD). After the first dose of the Moderna vaccine, 6/121 (5.0%) of recipients demonstrated a positive anti-RBD response, which increased to 38/110 (34.5%) of recipients after the second dose. Thus, more than half (72/110; 65.5%) of transplant recipients had no detectable anti-RBD response after the second vaccine dose.

The authors also measured the ability of the antibodies to neutralize virus, which is increasingly being recognized as a correlate of protection against SARS-CoV-2. 7/119 (5.9%) of participants had a positive neutralization response after the first dose, and 29/108 (26.9%) after the second dose of the vaccine. This left 79/108 (73.1%) of patients without a detectable antibody neutralization following dose two of the two-dose Moderna vaccine. Interestingly, while positive neutralizing ability was shown to correlate with positive anti-RBD levels, 28.5% of those with a positive anti-RBD response were negative in their neutralization response.

Cell-mediated immunity was also assessed in a subset of 48 patients. Following the first dose of the vaccine, 4/40 (10%) of patients in this subgroup had a positive T-cell response, specifically the CD4+ T-cell response. Following the second dose, 23/48 (47.9%) had a positive CD4+ T-cell response. Notably, of the 26 patients in this subgroup (26/48; 54.2%) with no detectable anti-RBD response, 12 (12/26; 46.2%) demonstrated a strong T-cell response, highlighting the importance of studying this arm of the immune system in this patient population. Finally, the authors also determined that the Moderna vaccine was safe and well-tolerated among participants.

In conclusion, the authors considered the immunogenicity of the Moderna vaccine in the solid organ transplant patient population to be moderate, which underscores the need to continue to vaccinate and monitor vaccine effectiveness in this at-risk population.