TY - JOUR
T1 - Neutralizing antibodies to Omicron after the fourth SARS-CoV-2 mRNA vaccine dose in immunocompromised patients highlight the need of additional boosters
AU - Rescigno, Maria
AU - Agrati, Chiara
AU - Salvarani, Carlo
AU - Giannarelli, Diana
AU - Costantini, Massimo
AU - Mantovani, Alberto
AU - Massafra, Raffaella
AU - Zinzani, Pier Luigi
AU - Morrone, Aldo
AU - Notari, Stefania
AU - Matusali, Giulia
AU - Pinter, Giuseppe Lauria
AU - Uccelli, Antonio
AU - Ciliberto, Gennaro
AU - Baldanti, Fausto
AU - Locatelli, Franco
AU - Silvestris, Nicola
AU - Sinno, Valentina
AU - Turola, Elena
AU - Lupo-Stanghellini, Maria Teresa
AU - Apolone, Giovanni
PY - 2023
Y1 - 2023
N2 - Introduction: Immunocompromised patients have been shown to have an impaired immune response to COVID-19 vaccines. Methods: Here we compared the B-cell, T-cell and neutralizing antibody response to WT and Omicron BA.2 SARS-CoV-2 virus after the fourth dose of mRNA COVID-19 vaccines in patients with hematological malignancies (HM, n=71), solid tumors (ST, n=39) and immune-rheumatological (IR, n=25) diseases. The humoral and T-cell responses to SARS-CoV-2 vaccination were analyzed by quantifying the anti-RBD antibodies, their neutralization activity and the IFN-γ released after spike specific stimulation. Results: We show that the T-cell response is similarly boosted by the fourth dose across the different subgroups, while the antibody response is improved only in patients not receiving B-cell targeted therapies, independent on the pathology. However, 9% of patients with anti-RBD antibodies did not have neutralizing antibodies to either virus variants, while an additional 5.7% did not have neutralizing antibodies to Omicron BA.2, making these patients particularly vulnerable to SARS-CoV-2 infection. The increment of neutralizing antibodies was very similar towards Omicron BA.2 and WT virus after the third or fourth dose of vaccine, suggesting that there is no preferential skewing towards either virus variant with the booster dose. The only limited step is the amount of antibodies that are elicited after vaccination, thus increasing the probability of developing neutralizing antibodies to both variants of virus. Discussion: These data support the recommendation of additional booster doses in frail patients to enhance the development of a B-cell response directed against Omicron and/or to enhance the T-cell response in patients treated with anti-CD20.
AB - Introduction: Immunocompromised patients have been shown to have an impaired immune response to COVID-19 vaccines. Methods: Here we compared the B-cell, T-cell and neutralizing antibody response to WT and Omicron BA.2 SARS-CoV-2 virus after the fourth dose of mRNA COVID-19 vaccines in patients with hematological malignancies (HM, n=71), solid tumors (ST, n=39) and immune-rheumatological (IR, n=25) diseases. The humoral and T-cell responses to SARS-CoV-2 vaccination were analyzed by quantifying the anti-RBD antibodies, their neutralization activity and the IFN-γ released after spike specific stimulation. Results: We show that the T-cell response is similarly boosted by the fourth dose across the different subgroups, while the antibody response is improved only in patients not receiving B-cell targeted therapies, independent on the pathology. However, 9% of patients with anti-RBD antibodies did not have neutralizing antibodies to either virus variants, while an additional 5.7% did not have neutralizing antibodies to Omicron BA.2, making these patients particularly vulnerable to SARS-CoV-2 infection. The increment of neutralizing antibodies was very similar towards Omicron BA.2 and WT virus after the third or fourth dose of vaccine, suggesting that there is no preferential skewing towards either virus variant with the booster dose. The only limited step is the amount of antibodies that are elicited after vaccination, thus increasing the probability of developing neutralizing antibodies to both variants of virus. Discussion: These data support the recommendation of additional booster doses in frail patients to enhance the development of a B-cell response directed against Omicron and/or to enhance the T-cell response in patients treated with anti-CD20.
KW - Omicron neutralization
KW - SARS-CoV-2 mRNA vaccine
KW - T cell response
KW - cross immunity
KW - humoral response
KW - immunocompromised patients
KW - Omicron neutralization
KW - SARS-CoV-2 mRNA vaccine
KW - T cell response
KW - cross immunity
KW - humoral response
KW - immunocompromised patients
UR - http://hdl.handle.net/10807/229765
U2 - 10.3389/fimmu.2023.1104124
DO - 10.3389/fimmu.2023.1104124
M3 - Article
SN - 1664-3224
VL - 14
SP - 1
EP - 10
JO - Frontiers in Immunology
JF - Frontiers in Immunology
ER -