Kidney transplant recipients do not produce as robust an antibody response to COVID-19 vaccines as otherwise healthy individuals

CITF-funded research from Drs. Matthew Oliver and Michelle Hladunewich (University of Toronto), now published in Transplantation Direct, found that over 50% of kidney transplant recipients (KTRs) lacked Omicron-specific neutralizing antibodies one month following a third vaccine dose. Antibody levels in those that developed the Omicron-specific antibodies were well preserved at 3 months.

Fewer KTRs developed an antibody response to Omicron as compared with their response to the original SARS-CoV-2 virus, or Delta and Beta variants. In contrast, 100% of those in the non-KTR control group developed neutralizing antibodies, although in this group, too, the response to Omicron was several times lower than for other variants. The amount of anti-receptor binding domain (RBD) antibodies a person produces may identify patients with a detectable Omicron-neutralizing antibody response.

This study is a collaboration between CITF-funded researchers Drs. Darren Yuen and Caitriona McEvoy from Unity Health Toronto and Dr. Michelle A. Hladunewich from the University of Toronto.

Key points:

• At a median of 26.5 days post-third vaccine dose, 75% and 88.6% of KTR participants were seropositive for the anti-receptor binding domain (RBD) and anti-spike (S), antibodies respectively. Three months post-dose 3, this was 57.7% and 88.5%, respectively.
• One-month following a third dose, the proportion of KTR participants with neutralizing antibodies against Omicron (20/44) was significantly lower than those with detectable neutralizing antibodies against the original virus (32/44), Delta (28/44) and Beta (25/44) variants.
• Moreover, the level of neutralizing antibody responses in patients with detectable levels at one month post third dose was several fold-lower for Beta (3.4-fold), Delta (1.8-fold), and Omicron (11.51-fold) as compared to the original virus. Three months post dose three, the level of neutralizing antibodies was lower than at the one month timepoint. However, the proportion of participants with detectable neutralizing antibodies was largely unchanged.
• Surprisingly, KTRs with detectable neutralizing antibody against Omicron achieved antibody levels comparable to non-transplanted healthy controls.
• Serum levels of anti-spike and anti-RBD antibodies were significantly higher in people who developed a neutralizing response against Omicron and who had detectable neutralizing antibodies against any one variant. This finding suggested higher levels of these antibodies may correlate with Omicron neutralization capacity.
• Individuals lacking a detectable Omicron neutralizing response tended to be older, have a longer transplant period, have a lower estimated glomerular filtration rate (eGFR)A glomerular filtration rate (eGFR) is a blood test that checks how well your kidneys are working., and have received mainly deceased donor organs.

This paper provides further evidence that the overall immune response to a three-dose vaccine regimen in KTRs remains inferior to the immunocompetent population, suggesting that alternative strategies may be necessary to induce a protective response against SARS-CoV-2 in transplanted patients.

44 kidney transplant recipients were enrolled in the study and blood samples were taken pre-and post-third dose. The median age of this group was 55.5 years and 79.5% of the participants were male. 26 of the 44 individuals were further assessed at 3 months post dose-3. The comparator group consisted of 13 healthy individuals with a median age of 46 years, of whom 30.7% males.