SARS-CoV-2 BA.4/5 Spike recognition and neutralization elicited after the third dose of mRNA vaccine


The SARS-CoV-2 Omicron BA.4 and BA.5 subvariants have recently emerged, with BA.5 becoming the dominant circulating strain in many countries. Both variants share the same Spike glycoprotein sequence which contains a large number of mutations, raising concerns about vaccine efficacy. In this study, we evaluated the ability of plasma from a cohort of individuals that received three doses of mRNA vaccine to recognize and neutralize the BA.4/5 Spike. We observed that BA.4/5 Spike is markedly less recognized and neutralized compared to the D614G and Omicron BA.2 Spike variants. Individuals who have been infected before or after vaccination present better humoral responses than SARS-CoV-2 naive vaccinated individuals, thus indicating that hybrid immunity generates better humoral responses against this subvariant.

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. 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.


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.


I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as 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).


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Data Availability

All data produced in the present work are contained in the manuscript

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