No Difference in Antibody or Humoral Responses Among Kidney Transplant Recipients Vaccinated with a 3rd Dose of mRNA or Adenovirus Vector Vaccine

1. In kidney transplant recipients (KTRs) who had no antibody response after a 2^nd mRNA COVID-19 vaccine dose, there was no significant difference in antibody or humoral responses between KTRs 4 weeks after receiving an mRNA or adenovirus vector vaccine 3^rd dose.

2. 22% of these KTRs had a neutralizing antibody response and 8.6% had a humoral response to the 3^rd dose respectively.

3. Predictors associated with greater likelihood of immune response included not being on triple-maintenance immunosuppression, lower levels of torque teno virus, and longer time elapsed since the last kidney transplant.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Due to immunosuppression, kidney transplant recipients (KTRs) are considered high risk for contracting a severe COVID-19 infection. Even with 2 doses of mRNA vaccine, trials in Israel and the United States found that 54% and 38% of KTRs developed an antibody response respectively. Other risk factors for a lack of antibody response include being treated with co-stimulation blockade (with a 6% response rate), less time elapsed since transplant, and lymphocyte-depleting induction therapy. Some strategies hypothesize to improve this response include additional doses and heterologous vaccination with an adenovirus vector vaccine, since recent studies have shown greater antibody and humoral responses from heterologous versus homologous vaccination. Therefore, the aim of the current randomized controlled trial was to compare antibody and humoral responses after a 3^rd dose, in KTRs who had no antibody response 4 weeks after their 2nd mRNA dose, with the 3^rd dose being either homologous (also mRNA) or heterologous (adenovirus vector). This single-centre trial based in Austria used the BNT162b2 (Pfizer) or mRNA-1273 (Moderna) vaccine for the homologous group, and an Ad26COVS1 (Johnson & Johnson) vaccine for the heterologous group. After 4 weeks, the results showed no statistically significant difference in antibody or humoral response. Humoral response was particularly low, with an 8.6% response rate. Although this study found no difference in response, the small sample size (197 patients) meant that only differences greater than 20% could be detected. As well, the study did not evaluate clinical outcomes such as symptomatic COVID-19 infection, since immunologic markers may not correlate exactly to protection from severe disease.

Click here to read the study in JAMA Internal Medicine

Relevant Reading: Reduced humoral response to mRNA SARS-CoV-2 BNT162b2 vaccine in kidney transplant recipients without prior exposure to the virus

In-Depth [randomized controlled trial]: The study population consisted of 197 KTRs, 58% male, with a mean (SD) age of 61.2 (12.4) years. These patients had previously received 2 doses of an mRNA vaccine, with no antibody response found at 4 weeks. 99 were randomized to the homologous (mRNA) group, and 98 to the heterologous (adenovirus vector) group. The antibody and humoral responses were measured between 29 and 42 days post-vaccination, with the humoral response being measured by a spike protein specific interferon-γ release assay (IGRA). Overall, an antibody response of greater than 0.8 U/mL was found in 35% of those receiving an mRNA 3^rd dose, and 42% of those receiving an adenovirus vector 3^rd dose, which was not a significant difference (odds ratio 1.31, 95% CI 0.71-2.44, p = 0.38). As well, only 22% of the antibody responses overall showed neutralizing capacity: This was not significantly different for the mRNA and vector 3^rd doses, at 6% and 11% respectively (OR 1.95, 95% CI 0.63-6.72, p = 0.22). In regards to T-cell response, only 17 (8.6%) KTRs showed reactivity, defined as >0.1 IU/mL, with 9 in the mRNA and 8 in the vector groups (OR 0.86, 95% CI 0.27-2.64, p = 0.80). Furthermore, factors associated with a greater likelihood of antibody response included not being on triple-maintenance immunosuppression (OR 3.59, 95% CI 1.33-10.75, p = 0.01), lower levels of torque teno virus (OR 0.92, 95% CI 0.88-0.96, p < 0.001 per doubling of TTV copies/mL), and a longer time elapsed since the last kidney transplant (OR 1.44, 95% CI 1.15-1.83, p = 0.002 per doubling of years). In conclusion, there was no significant difference in antibody or humoral responses in kidney transplant recipients, receiving their 3^rd dose of a homologous or heterologous COVID-19 vaccine.

Image: PD

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