Kidney Transplant Recipients Develop Nasal Mucosal Antibodies to SARS‐CoV‐2 With ACE2‐Inhibiting Activity Following mRNA Vaccination

Background Less than 60% of kidney transplant recipients (KTRs) become IgG seropositive for the viral spike (S) antigen following two COVID‐19 vaccine doses, with a third dose increasing these numbers further. Mucosal antibodies play a critical role in protection against SARS‐CoV‐2 (re)infection; however, the presence and functionality of these antibodies after vaccination have not been well‐studied in high‐risk groups with reduced vaccine immunogenicity. Methods We assessed the concentration of ancestral S‐specific antibodies in the nasal mucosa and in serum as well as their capacity to neutralize binding of the receptor‐binding domain (RBD) to the ACE2 receptor in KTRs after two, three, and/or four vaccinations, compared with an age‐matched control group after two vaccine doses. Results KTRs showed an increase in nasal and serum S‐specific IgG and S‐specific IgA geometric mean concentrations (GMCs) as well as ACE2 binding inhibition at 28 days after both two‐dose and additional vaccinations compared to baseline, although postvaccination GMCs remained lower than in the control group. We observed a high correlation between nasal and serum antibody levels ( r S > 0.63) and ACE2 inhibiting capacity ( r S > 0.65). Furthermore, nasal S‐specific IgG, and to a lesser extent IgA, was correlated with nasal ACE2 binding inhibition ( r S > 0.64 and 0.5). Conclusions KTRs develop nasal mucosal antibodies, which are able to inhibit binding to ACE2 after COVID‐19 vaccination, but at a lower concentration than controls. Mucosal sampling provides an accessible and minimally invasive addition to measuring serum antibodies for monitoring the response to vaccination at a population level.