Defective neutralizing antibody response to SARS-CoV-2 in vaccinated dialysis patients

Bassi, J.; Giannini, O.; Silacci-Fregni, C.; Pertusini, L.; Hitz, P.; Terrot, T.; Franzosi, Y.; Muoio, F.; Saliba, C.; Meury, M.; Dellota, E.; Dillen, J.; Hernandez, P.; Czudnochowski, N.; Cameroni, E.; Beria, N.; Ventresca, M.; Badellino, A.; Lavorato-Hadjeres, S.; Lecchi, E.; Bonora, T.; Mattiolo, M.; Trinci, G.; Garzoni, D.; Bonforte, G.; Forni-Ogna, V.; Giunzioni, D.; Berwert, L.; Gupta, R. K.; Ferrari, P.; Ceschi, A.; Cippa', P.; Corti, D.; Lanzavecchia, A.; Piccoli, L.

Patients on dialysis are at risk of severe course of SARS-CoV-2 infection. Understanding the neutralizing activity and coverage of SARS-CoV-2 variants of vaccine-elicited antibodies is required to guide prophylactic and therapeutic COVID-19 interventions in this frail population. By analyzing plasma samples from 130 hemodialysis (HD) and 13 peritoneal dialysis patients after two doses of BNT162b2 or mRNA-1273 vaccines, we found that 35% of the patients had low-level or undetectable IgG antibodies to SARS-CoV-2 Spike (S). Neutralizing antibodies against the vaccine-matched SARS-CoV-2 and Delta variant were low or undetectable in 49% and 77% of patients, respectively, and were further reduced against other emerging variants. The fraction of non-responding patients was higher in SARS-CoV-2-naive HD patients immunized with BNT162b2 (66%) than those immunized with mRNA-1273 (23%). The reduced neutralizing activity correlated with low antibody avidity, consistent with a delayed affinity maturation of SARS-CoV-2 S-specific B cells. These data indicate that dialysis patients should be considered for an additional boost and other therapeutic strategies, including early immunotherapy with monoclonal antibodies.