Frontiers in Immunology (Jan 2023)

Neutralizing antibodies to Omicron after the fourth SARS-CoV-2 mRNA vaccine dose in immunocompromised patients highlight the need of additional boosters

  • Maria Rescigno,
  • Maria Rescigno,
  • Chiara Agrati,
  • Chiara Agrati,
  • Carlo Salvarani,
  • Carlo Salvarani,
  • Diana Giannarelli,
  • Massimo Costantini,
  • Alberto Mantovani,
  • Alberto Mantovani,
  • Alberto Mantovani,
  • Raffaella Massafra,
  • Pier Luigi Zinzani,
  • Pier Luigi Zinzani,
  • Aldo Morrone,
  • Stefania Notari,
  • Giulia Matusali,
  • Giuseppe Lauria Pinter,
  • Giuseppe Lauria Pinter,
  • Antonio Uccelli,
  • Antonio Uccelli,
  • Gennaro Ciliberto,
  • Fausto Baldanti,
  • Fausto Baldanti,
  • Franco Locatelli,
  • Franco Locatelli,
  • Nicola Silvestris,
  • Valentina Sinno,
  • Elena Turola,
  • Maria Teresa Lupo-Stanghellini,
  • Giovanni Apolone,
  • the VAX4FRAIL study Group,
  • Giovanni Apolone,
  • Alberto Mantovani,
  • Massimo Costantini,
  • Nicola Silvestris,
  • Chiara Agrati,
  • Fabio Ciceri,
  • Franco Locatelli,
  • Alberto Mantovani,
  • Aldo Morrone,
  • Massimo Tommasino,
  • Nicola Silvestris,
  • Giuseppe Lauri Pinter,
  • Antonio Uccelli,
  • Pier Luigi Zinzani,
  • Paolo Corradini,
  • Gennaro Ciliberto,
  • Carlo Salvarani,
  • Antonio Uccelli,
  • Maria Rescigno,
  • Daniela Fenoglio,
  • Roberta Mortarini,
  • Laura Conti,
  • Chiara Mandoj,
  • Michela Lizier,
  • Stefania Croci,
  • Vito Garrisi,
  • Fulvio Baggi,
  • Tiziana Lazzarotto,
  • Francesca Bonifazi,
  • Concetta Quintarelli,
  • Rita Carsetti,
  • Enrico Girardi,
  • Aurora Bettini,
  • Veronica Bordoni,
  • Concetta Castilletti,
  • Eleonora Cimini,
  • Rita Casetti,
  • Francesca Colavita,
  • Flavia Cristofanelli,
  • Massimo Francalancia,
  • Simona Gili,
  • Delia Goletti,
  • Giulia Gramigna,
  • Germana Grassi,
  • Daniele Lapa,
  • Sara Leone,
  • Davide Mariotti,
  • Giulia Matusali,
  • Silvia Meschi,
  • Stefania Notari,
  • Enzo Puro,
  • Marika Rubino,
  • Alessandra Sacchi,
  • Eleonora Tartaglia,
  • Paolo Corradini,
  • Silvia Damian,
  • Vincenzo Marasco,
  • Filippo de Braud ,
  • Maria Teresa Lupo Stanghellini,
  • Lorenzo Dagna,
  • Francesca Ogliari,
  • Massimo Filippi,
  • Alessandro Bruno,
  • Gloria Catalano,
  • Rosamaria Nitti,
  • Andrea Mengarelli,
  • Francesco Marchesi,
  • Giancarlo Paoletti e Gabriele Minuti,
  • Elena Papa,
  • Elena Azzolini,
  • Luca Germagnoli,
  • Carlo Selmi,
  • Maria De Santis,
  • Carmelo Carlo-Stella,
  • Alexia Bertuzzi,
  • Francesca Motta,
  • Angela Ceribelli,
  • Chiara Miggiano,
  • Giulia Fornasa,
  • Fausto Baldanti,
  • Sara Monti,
  • Carlo Maurizio Montecucco,
  • Aldo Morrone,
  • Dario Graceffa,
  • Maria Grazia Catanoso,
  • Monica Guberti,
  • Carmine Pinto,
  • Francesco Merli,
  • Franco Valzania,
  • Rosa Divella,
  • Antonio Tufaro,
  • Vito Garrisi,
  • Sabina Delcuratolo,
  • Mariana Miano ,
  • Carlo Antozzi,
  • Silvia Bonanno Rita Frangiamore,
  • Lorenzo Maggi ,
  • Antonio Uccelli,
  • Paolo Pronzato,
  • Matilde Inglese,
  • Carlo Genova,
  • Caterina Lapucci,
  • Alice Laroni,
  • Ilaria Poiré,
  • Marco Fusconi,
  • Vittorio Stefoni,
  • Maria Abbondanza Pantaleo ,
  • Diana Giannarelli,
  • Valentina Sinno,
  • Serena Di Cosimo ,
  • Elena Turola,
  • Iolanda Pulice,
  • Roberta Mennitto Fondazione,
  • Stefania Trinca,
  • Giulia Piaggio,
  • Chiara Pozzi,
  • Irene Cassaniti,
  • Alessandro Barberini,
  • Sabina Delcuratolo,
  • Rinaldi Elena,
  • Federica Bortone,
  • Maria Giovanna Dal Bello,
  • Silvia Corazza

DOI
https://doi.org/10.3389/fimmu.2023.1104124
Journal volume & issue
Vol. 14

Abstract

Read online

IntroductionImmunocompromised patients have been shown to have an impaired immune response to COVID-19 vaccines.MethodsHere 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.ResultsWe 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.DiscussionThese 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.

Keywords