On the 24 th November 2021 the sequence of a new SARS CoV-2 viral isolate Omicron-B.1.1.529 was announced, containing far more mutations in Spike (S) than previously reported variants. Neutralization titres of Omicron by sera from vaccinees and convalescent subjects infected with early pandemic as well as Alpha, Beta, Gamma, Delta are substantially reduced or fail to neutralize. Titres against Omicron are boosted by third vaccine doses and are high in cases both vaccinated and infected by Delta. Mutations in Omicron knock out or substantially reduce neutralization by most of a large panel of potent monoclonal antibodies and antibodies under commercial development. Omicron S has structural changes from earlier viruses, combining mutations conferring tight binding to ACE2 to unleash evolution driven by immune escape, leading to a large number of mutations in the ACE2 binding site which rebalance receptor affinity to that of early pandemic viruses.

SARS-CoV-2 has undergone progressive change with variants conferring advantage rapidly becoming dominant lineages e.g. B.1.617. With apparent increased transmissibility variant B.1.617.2 has contributed to the current wave of infection ravaging the Indian subcontinent and has been designated a variant of concern in the UK. Here we study the ability of monoclonal antibodies, convalescent and vaccine sera to neutralize B.1.617.1 and B.1.617.2 and complement this with structural analyses of Fab/RBD complexes and map the antigenic space of current variants. Neutralization of both viruses is reduced when compared with ancestral Wuhan related strains but there is no evidence of widespread antibody escape as seen with B.1.351. However, B.1.351 and P.1 sera showed markedly more reduction in neutralization of B.1.617.2 suggesting that individuals previously infected by these variants may be more susceptible to reinfection by B.1.617.2. This observation provides important new insight for immunisation policy with future variant vaccines in non-immune populations.

Highlights d Generated 674 antibodies from patients infected with SARS-CoV-2 Beta variant d 18 of 27 most potent mAbs target the 3 mutations in Beta RBD d A major response to N501Y includes a public IgVH4-39 sequence d Two antibodies recognize a neutralizing epitope conserved between SARS-CoV-1 and -2

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2 Public Health England (PHE) ObjectivesTo enhance the research value and capability of its primary care database, the Clinical Practice Research Datalink (CPRD) has collaborated with Public Health England (PHE)âĂŹs National Cancer Registration and Analysis Service to facilitate access to linked cancer registration data for use in research, pharmacovigilance, drug monitoring and health outcomes analysis. Since 2009, access to this linked resource has been co-managed by CPRD and PHE, through two parallel, independent approvals processes: (a) the MHRA Independent Scientific Advisory Committee (ISAC) and (b) the PHE Office for Data Release (ODR). In upholding the Office for Life Science Ministerial Industry Strategy Group (Health Data Programme)'s vision to minimise process barriers to accessing real world data, CPRD and PHE have worked together to unify and streamline these two processes into a single end-to-end application and approval process. ApproachEach organisation reviewed each other's approval processes to achieve an improved mutual understanding of the respective organisation's governance approach, the risk based assessments applied to disclosure risk, risk appetites and policies, with the goal to harmonise these into a single approval process. ResultsCPRD and PHE are finalising a contract establishing a clear operating framework allowing CPRD to grant approval to researchers for the use of linked cancer registry data. The contract names CPRD as a joint data controller and sets out the purposes for processing, the manner of processing and the means by which joint data controller responsibilities will be satisfied. An associated service level agreement is in discussion which will enable robust timelines and performance management for both organisations. These developments are important milestones towards achieving the single approval process by allowing CPRD to review applications for cancer registry data in-house, simultaneously to the ISAC review. ConclusionThe strong relationship built between CPRD and PHE, and willingness to develop a single application and approval process, will strengthen and streamline access to these data, whilst assuring patients and the public that scientific integrity is maintained and proportionate information governance checks are in place. Upon completion of this work, applicants will experience associated faster review and feedback time, ultimately leading to faster approvals. Researchers wishing to utilise these linked data will soon be able to submit one application to ISAC, have one point of contact and one approval.