While SARS-CoV-2 mRNA vaccination has been shown to be safe and effective in the general population, immunocompromised solid organ transplant recipients (SOTR) were reported to have impaired immune responses after one or two doses of vaccine. In this study, we examined humoral responses induced after the second and the third dose of mRNA vaccine in different SOTR (kidney, liver, lung and heart). Compared to a cohort of SARS-CoV-2 naive immunocompetent health care workers (HCW), the second dose induced weak humoral responses in SOTR, except for the liver recipients. The third dose boosted these responses but they did not reach the same level as in HCW. Interestingly, while the neutralizing activity against Delta and Omicron variants remained very low after the third dose, Fc-mediated effector functions in SOTR reached similar levels as in the HCW cohort. Whether these responses will suffice to protect SOTR from severe outcome remains to be determined.

The authors have declared no competing interest.

This work was supported by le Ministere de l Economie et de l Innovation du Quebec, Programme de soutien aux organismes de recherche et d innovation to A.F. and by the Fondation du CHUM. This work was also supported by a CIHR foundation grant #352417, by a CIHR operating Pandemic and Health Emergencies Research grant #177958, to A.F., and by an Exceptional Fund COVID-19 from the Canada Foundation for Innovation (CFI) #41027 to D.E.K. and A.F. This work was also supported by a FRQS Pandemic Initiatives COVID-19 grant #308941 to M.J.H and in-kind contribution from Canadian Donation and Transplantation Research Program (CDTRP). Work on variants presented was also supported by the Sentinelle COVID Quebec network led by the LSPQ in collaboration with Fonds de Recherche du Quebec Sante (FRQS) to A.F. A.F. is the recipient of Canada Research Chair on Retroviral Entry no. RCHS0235 950-232424. M.-J. H. holds the Shire Chair in Nephrology, Transplantation and Renal Regeneration of Universite de Montreal. C.T holds the Pfizer - Universite de Montreal Chair on HIV translational research. V.M.L. is supported by a FRQS Junior 1 salary award. D.E.K. is a FRQS Merit Research Scholar. G.B.B. is the recipient of a FRQS PhD fellowship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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All work was conducted in accordance with the Declaration of Helsinki in terms of informed consent and approval by an appropriate institutional board. Blood samples were obtained from donors who consented to participate in this research project at Centre Hospitalier de l Universite de Montreal (CHUM). The study was approved by the Centre Hospitalier de l Universite de Montreal Institutional Review Board (no. 19.381 and 21.001).

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