SARS-CoV-2 Omicron subvariants Spike recognition and neutralization elicited after the third dose of mRNA vaccine

Several SARS-CoV-2 Omicron subvariants have recently emerged, becoming the dominant circulating strains in many countries. These variants contain a large number of mutations in their Spike glycoprotein, raising concerns about vaccine efficacy. In this study, we evaluate the ability of plasma from a cohort of individuals that received three doses of mRNA vaccine to recognize and neutralize these Omicron subvariant Spikes. We observed that BA.4/5 and BQ.1.1 Spikes are markedly less recognized and neutralized compared to the D614G and the other Omicron subvariant Spikes tested. Also, individuals who have been infected before or after vaccination present better humoral responses than SARS-CoV-2 naïve vaccinated individuals, thus indicating that hybrid immunity generates better humoral responses against these subvariants. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement 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, by an Exceptional Fund COVID-19 from the Canada Foundation for Innovation (CFI) #41027 to A.F. and by a FRQS Merit Research Scholar award (# 268471) to D.E.K. 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. This work was also partially supported by a CIHR COVID-19 rapid response grant (OV3 170632) and CIHR stream 1 SARS-CoV-2 Variant Research to M.C. A.F. is the recipient of Canada Research Chair on Retroviral Entry no. RCHS0235 950-232424. M.C is a Tier II Canada Research Chair in Molecular Virology and Antiviral Therapeutics (950-232840). C.T. is the Pfizer/Universite de Montreal Chair on HIV translational research. A.T. was supported by MITACS Acceleration postdoctoral fellowship. M.B. was the recipient of a CIHR master scholarship award. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We declare no competing interests. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: 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 Institutional Review Boards (no. 19.381 at CHUM) I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present work are contained in the manuscript