Omicron BA.4/5 Neutralization and T-Cell Responses in Organ Transplant Recipients After Booster Messenger RNA Vaccine: A Multicenter Cohort Study.

BACKGROUND

In solid organ transplant (SOT) recipients, the primary vaccination series against Coronavirus Disease 2019 is 3 doses followed by boosters. We determined whether a fourth dose booster induced Omicron BA.4/5 neutralizing antibodies (nAbs) and T cells in a large multicenter cohort study.

METHODS

Serum was collected 4-6 weeks post-third and post-fourth doses of messenger RNA vaccine in 222 SOT recipients. nAbs were measured using a pseudovirus neutralization assay that targeted the Omicron BA.4/5 spike protein. A subset underwent T-cell testing.

RESULTS

The median age of the cohort was 63 years (interquartile range [IQR], 50-68) with 61.7% men. BA.4/5 nAb detection increased from 26.6% (59 of 222) post-third dose to 53.6% (119 of 222) post-fourth dose (P < .0001). In patients with breakthrough infection prior to the fourth dose (n = 27), nAbs were detected in 77.8% and median nAb titers were significantly higher compared with those with 4 vaccine doses alone (P < .0001). Factors associated with a low BA.4/5 neutralization response after the fourth dose were older age (odds ratio [OR], 0.96; 95% confidence interval [CI], .94-.99), mycophenolate use (OR, 0.39; 95% CI, .20-.77) and prednisone use (OR, 0.34; 95% CI, .18-.63), and vaccine type (OR, 0.72; 95% CI, .51-.99), while breakthrough infection prior to the 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 4 doses and were identified in 76.9% of patients at a median frequency of 213/106 cells (IQR, 98-650).

CONCLUSIONS

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 who are older and on mycophenolate and prednisone need additional preventative strategies.

Informations de copyright

© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: [e-mail].

Déclaration de conflit d'intérêts

Potential conflicts of interest. D. Kumar reports research grants from Roche and GSK and consulting fees from Roche, GSK, Merck, and Medscape. D. Kabbani reports a clinical trials grant from Pulmocide, a research grant from AVIR pharma, an educational grant from GSK, and honoraria for lectures from GSK and AVIR pharma. A. H. reports research grants and consulting fees from Merck. A.-C. G. reports receipt of funds from a research contract with Providence Therapeutics Holdings, Inc (unrelated to this work); co-PI/collab in grants from CIHR and the Ontario Research Fund on SARS-CoV-2; and unpaid roles as chair of the CIHR Institute of Genetics Advisory Board, former chair and current member of the National Research Council of Canada (NRC) HHT division, member of working parties for the COVID-19 Immunity Task Force, and pillar lead on functional genomics and structure-function at CoVaRR-Net. S. B. reports a team grant from the Vancouver Coastal Health Research Institute and the Transplant Research Foundation of British Columbia (paid to institution); consulting fees from AstraZeneca and GSK; and payment or honoraria from Merck for speaking engagements or presentations. M.-J. H. reports roles as a chairperson for the Governing Council at the Canadian Institutes of Health Research, as a Mila board member at the Institute of Artificial Intelligence, and as a board member of Hopital Ste-Justine in Quebec, Canada. V. H. F. reports grants or contracts (paid to the author’s institution) from the Canadian Institutes of Health Research, the COVID-19 Immunity Task Force, the University Health Network–Transplant Program Strategic Clinical Project Fund, and the Mount Sinai Hospital University Health Network Academic Medical Organization COVID19 Innovation Fund Project. V. G. H. reports a research stipend from the National Health Medical Research Council post graduate PhD scholarship (unrelated to this work). All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.