Introduction: We sought to evaluate the humoral response to SARS-CoV-2 vaccination in a cohort of kidney transplant (KT) recipients and to identify factors associated with poor humoral immune response.

Method: Serum samples collected from COVID-19 vaccinated kidney transplant (KT) recipients from 3/1/21-4/26/21 were tested for COVID-19 antibodies using a novel multi-antigen detection Luminex platform (BioRad). We measured the specific anti-SARS-CoV-2 IgG antibodies against the individual components of the trimeric spike protein, namely spike 1 (S1), spike 2 (S2) and receptor-binding domains (RBDs). In addition, documentation of previous infection was assessed by measuring anti-nucleocapsid antibodies.

Results: The study cohort enrolled 104 KT recipients that underwent assessment of serological responses at a median 3 weeks (IQR: 1.6-4.9) after vaccination. The majority of patients received either the BNT162b2 (50%) or mRNA-1273 (47.1%), with only 2.9% of patients receiving the Ad26.COV2.S vaccine. Overall, 32.7% of patients became seropositive with a median anti-S1 IgG and anti-RBD IgG levels of 403 BAU/ml (IQR:82-800) and 206 BAU/ml (IQR:41-800). In terms of predictive factors for vaccine response, we identified that those on an immunosuppressive regimen containing MMF were less likely to develop a seroconversion (relative risk [RR], 0.54 [95% CI, 0.31-0.94]; p=0.03). By contrast, patients with evidence of previous infection as documented by anti-nucleocapsid positivity were significantly more likely to became seropositive (RR, 2.73; 95%CI, 1.7-4.39; p<0.001). Regarding the temporal evolution of humoral response, there is a clear tendency for a weaning of antibody response over time. In patients with a vaccine response, the median titer of anti-RBD antibodies decreased from 800 BAU/ml (IQR:257-800), in patients with serum samples within 2 weeks after vaccination, to 168 BAU/ml (IQR:74-641), in patients with samples taken after more than 4 weeks post-vaccination (p=0.15). Similarly, the anti-S1 IgG antibody titers were higher in patients with serum samples taken early after vaccination [636 BAU/ml (IQR:276-800), for 0-2 weeks; 579 BAU/ml (IQR:39-800), for 2-4 weeks and 97 BAU/ml (IQR:37-251) for > 4 weeks; p=0.05]. In multivariate logistic regression analysis, we identified the presence of anti-nucleocapsid IgG antibodies as being independently associated with approximately 8-fold higher chance for a seroconversion (HR, 7.96; 95%CI, 1.26-50.1), while use of MMF-containing immunosuppressive regimens decreased the chance of humoral response by approximately 66% (HR, 0.34; 95%CI, 0.1-1.11).

Conclusion: Kidney transplant recipients have a poor humoral immune response to a two-dose regimen of SARS-CoV-2 vaccine. Previous natural infection increase the likelihood for development a seroconversion, while MMF-containing regimens decreased vaccine responsiveness.