Live virus neutralisation testing in convalescent patients and subjects vaccinated against 19A, 20B, 20I/501Y.V1 and 20H/501Y.V2 isolates of SARS-CoV-2

Background SARS-CoV-2 mutations appeared recently and can lead to conformational changes in the spike protein and probably induce modifications in antigenicity. In this study, we wanted to assess the neutralizing capacity of antibodies to prevent cell infection, using a live virus neutralisation test. Methods Sera samples were collected from different populations: two-dose vaccinated COVID-19-naïve healthcare workers (HCWs; Pfizer-BioNTech BNT161b2), 6-months post mild COVID-19 HCWs, and critical COVID-19 patients. We tested various clades such as 19A (initial one), 20B (B.1.1.241 lineage), 20I/501Y.V1 (B.1.1.7 lineage), and 20H/501Y.V2 (B.1.351 lineage). Results No significant difference was observed between the 20B and 19A isolates for HCWs with mild COVID-19 and critical patients. However, a significant decrease in neutralisation ability was found for 20I/501Y.V1 in comparison with 19A isolate for critical patients and HCWs 6-months post infection. Concerning 20H/501Y.V2, all populations had a significant reduction in neutralising antibody titres in comparison with the 19A isolate. Interestingly, a significant difference in neutralisation capacity was observed for vaccinated HCWs between the two variants whereas it was not significant for the convalescent groups. Conclusion Neutralisation capacity was slightly reduced for critical patients and HCWs 6-months post infection. No neutralisation escape could be feared concerning the two variants of concern in both populations. The reduced neutralising response observed towards the 20H/501Y.V2 in comparison with the 19A and 20I/501Y.V1 isolates in fully immunized subjects with the BNT162b2 vaccine is a striking finding of the study. ### Competing Interest Statement Antonin Bal received a grant from bioMerieux and served as consultant for bioMerieux for work and research not related to this manuscript. Sophie Trouillet-Assant received a research grant from bioMerieux concerning previous works not related to this manuscript. The other authors have no relevant affiliations or financial involvement with any organisation or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. ### Funding Statement This research is being supported by Hospices Civils de Lyon and by Fondation des Hospices Civils de Lyon. The GIMAP team of the University Hospital of Saint-Etienne is supported by a donation from the ‘ASSE coeur-vert’ association (grant ref. no. COVID-19). ### 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: Written informed consent was obtained from all HCWs; ethics approval was obtained from the national review board for biomedical research in April 2020 (Comité de Protection des Personnes Sud Méditerranée I, Marseille, France; ID RCB 2020-A00932-37), and the study was registered on [ClinicalTrials.gov][1] ([NCT04341142][2]). Concerning critical patients, this study was approved by the ethics committee of the university hospital of Saint-Etienne (reference number IRBN512020/CHUSTE). All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. 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][1]. 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 GISAID accession numbers: EPI\_ISL\_1707038 EPI\_ISL\_1707039 EPI\_ISL\_1707040 EPI\_ISL\_768828 [1]: http://ClinicalTrials.gov [2]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT04341142&atom=%2Fmedrxiv%2Fearly%2F2021%2F05%2F11%2F2021.05.11.21256578.atom