Omicron BA.4/5 neutralization and T-cell responses in organ transplant recipients after Booster mRNA vaccine: a Multicenter Cohort Study

Victor H Ferreira; Matthew Ierullo; Faranak Mavandadnejad; Alexandra Kurtesi; Queenie Hu; W Rod Hardy; Victoria G Hall; Natalia Pinzon; Demitra Yotis; Anne-Claude Gingras; Sara Belga; Sarah Shalhoub; Marie-Josée Hébert; Atul Humar; Dima Kabbani; Deepali Kumar; PREVenT Study Group

doi:10.1093/cid/ciad175

Omicron BA.4/5 neutralization and T-cell responses in organ transplant recipients after Booster mRNA vaccine: a Multicenter Cohort Study

Clin Infect Dis. 2023 Mar 28;ciad175. doi: 10.1093/cid/ciad175. Online ahead of print.

Authors

Victor H Ferreira¹, Matthew Ierullo¹, Faranak Mavandadnejad¹, Alexandra Kurtesi², Queenie Hu², W Rod Hardy², Victoria G Hall¹, Natalia Pinzon¹, Demitra Yotis³, Anne-Claude Gingras^{2

4}, Sara Belga⁵, Sarah Shalhoub⁶, Marie-Josée Hébert⁷, Atul Humar¹, Dima Kabbani⁸, Deepali Kumar¹; PREVenT Study Group

Collaborators

Affiliations

¹ Ajmera Transplant Centre, University Health Network (UHN), Toronto, ON., Canada.
² Lunenfeld-Tanenbaum Research Institute at Mount Sinai Hospital, Sinai Health, Toronto, ON., Canada.
³ Canadian Donation and Transplantation Research Program (CDTRP), Edmonton, AB., Canada.
⁴ Department of Molecular Genetics, University of Toronto, Toronto, ON., Canada.
⁵ University of British Columbia, Vancouver, BC., Canada.
⁶ London Health Sciences Centre, London, ON., Canada.
⁷ Centre Hospitalier de L'Université de Montréal (CHUM), Montréal, QC., Canada.
⁸ University of Alberta, Edmonton, AB., Canada.

PMID: 36975097
DOI: 10.1093/cid/ciad175

Abstract

Background: In solid organ transplant (SOT) recipients, the primary vaccination series against COVID-19 is three doses followed by boosters. We determined whether a fourth dose booster induced Omicron BA.4/5 neutralizing antibodies and T-cells in a large multicenter cohort study.

Methods: Serum was collected 4-6 weeks post third and fourth dose of mRNA vaccine in 222 SOT recipients. Neutralizing antibodies (nAb) were measured using a pseudovirus neutralization assay targeting the Omicron BA.4/5 spike protein. A subset underwent T-cell testing.

Results: Median age of the cohort was 63 years (IQR 50-68) with 61.7% men. BA.4/5 nAb detection increased from 26.6%(59/222) post third dose to 53.6%(119/222) post fourth dose (p<0.0001). In patients with breakthrough infection prior to fourth dose (n=27), nAb were detected in 77.8% and median nAb titers were significantly higher compared to those with four vaccine doses alone (p<0.0001). Factors associated with a low BA.4/5 neutralization response after fourth dose were older age (OR 0.96, 95%CI 0.94-0.99), mycophenolate use (OR 0.39, 95%CI 0.20-0.77) and prednisone use (OR 0.34, 95%CI 0.18-0.63), and vaccine type (OR 0.72, 95%CI 0.51-0.99) while breakthrough infection prior to fourth dose (OR 3.6, 95%CI 1.3-9.9) was associated with a greater nAb response. Polyfunctional BA.4/5-specific CD4+ T-cells significantly increased after four doses and were identified in 76.9% of patients at a median frequency of 213 per 106 cells (IQR 98-650).

Conclusion: In summary, a booster significantly increases BA.4/5-specific neutralization and polyfunctional CD4+ T-cell responses, suggesting protection from severe disease even with new Omicron variants. However, SOT recipients that are older, on mycophenolate and prednisone need further preventative strategies.

Keywords: SARS-CoV-2; immunity; immunocompromised; mRNA vaccine; prospective.