Mapping the antigenic diversification of SARS-CoV-2

Large-scale vaccination campaigns have prevented countless hospitalizations and deaths due to COVID-19. However, the emergence of SARS-CoV-2 variants that escape from immunity challenges the effectiveness of current vaccines. Given this continuing evolution, an important question is when and how to update SARS-CoV-2 vaccines to antigenically match circulating variants, similar to seasonal influenza viruses where antigenic drift necessitates periodic vaccine updates. Here, we studied SARS-CoV-2 antigenic drift by assessing neutralizing activity against variants-of-concern (VOCs) of a unique set of sera from patients infected with a range of VOCs. Infections with D614G or Alpha strains induced the broadest immunity, while individuals infected with other VOCs had more strain-specific responses. Omicron BA.1 and BA.2 were substantially resistant to neutralization by sera elicited by all other variants. Antigenic cartography revealed that Omicron BA.1 and BA.2 are antigenically most distinct from D614G, associated with immune escape and likely requiring vaccine updates to ensure vaccine effectiveness. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was funded by: R.W.S. and C.A.R. are recipients of Vici grants from the Netherlands Organization for Scientific Research (NWO no. 91818627 for R.W.S.). C.A.R. and A.X.H. are also supported by an ERC Consolidator Award. This work was supported by the NWO ZonMw grant agreement no. 10150062010002 to M.D.dJ., and 10430072110003 to G.J. de Bree and the Public Health Service of Amsterdam Research & Development grant number 21-14 to M. Prins (RECoVERED). J.J.S. and M.K.B. are recipients of the NWO grant agreement no. 10430022010023 and 10430022010030. ### 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: The COSCA study, the RECoVERED study and the S3-study were conducted at the Amsterdam University Medical Centres, the Netherlands, and approved the medical ethical review board of the Amsterdam University Medical Centres (NL 73281.018.20, NL73759.018.20, NL73478.029.20, respectively). All individuals provided written informed consent before participating. 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 study are available upon reasonable request to the authors.