The development timeline of COVID-19 vaccines is unprecedented, with more than 300 vaccine developers active worldwide. 1 Vaccine candidates developed with various technology platforms targeting different epitopes of SARS-CoV-2 are in the pipeline. Vaccine developers are using a range of immunoassays with different readouts to measure immune responses after vaccination, making comparisons of the immunogenicity of different COVID-19 vaccine candidates challenging. In April, 2020, in a joint effort, the Coalition for Epidemic Preparedness Innovations (CEPI), the National Institute for Biological Standards and Control (NIBSC), and WHO provided vaccine developers and the entire scientific community with a research reagent for an anti-SARS-CoV-2 antibody. The availability of this material was crucial for facilitating the development of diagnostics, vaccines, and therapeutic preparations. This effort was an initial response when NIBSC, in its capacity as a WHO collaborating centre, was working on the preparation of the WHO International Standards. This work included a collaborative study that was launched in July, 2020, to test serum samples and plasma samples sourced from convalescent patients with the aim of selecting the most suitable candidate material for the WHO International Standards for anti-SARS-CoV-2 immunoglobulin. The study involved 44 laboratories from 15 countries and the use of live and pseudotype-based neutralisation assays, ELISA, rapid tests, and other methods. The outcomes of the study were submitted to WHO in November, 2020. The inter-laboratory variation was reduced more than 50 times for neutralisation and

Tetherin is an IFN-inducible restriction factor that inhibits HIV-1 particle release in the absence of the HIV-1 countermeasure, viral protein U (Vpu). Although ubiquitous in HIV-1 and simian immunodeficiency viruses from chimpanzees, greater spot nosed monkeys, mustached monkeys, and Mona monkeys, other primate lentiviruses do not encode a Vpu protein. Here we demonstrate that SIV from Tantalus monkeys (SIVtan) encodes an envelope glycoprotein (SIVtan Env) able to counteract tetherin from Tantalus monkeys, rhesus monkeys, sooty mangabeys, and humans, but not from pigs. We show that sensitivity to Vpu but not SIVtan Env can be transferred with the human tetherin transmembrane region. We also identify a mutation in the tetherin extracellular domain, which almost completely abolishes sensitivity of human tetherin to SIVtan Env without compromising antiviral activity or sensitivity to Vpu. SIVtan Env expression results in a reduction of surface tetherin, as well as reduction in tetherin co-localization with mature surface-associated virus. Immuno-electron microscopy reveals co-localization of SIVtan Env with tetherin in intracellular tubulo-vesicular structures, suggesting that tetherin is sequestered away from budding virions at the cell surface. Along with HIV-1 Vpu and SIV Nef, envelope glycoprotein is the third and most broadly active lentiviral-encoded tetherin countermeasure to be described. Our observations emphasize the importance of tetherin in protecting mammals against viral infection and suggest that HIV-1 Vpu inhibitors may select active envelope mutants.HIV ͉ restriction ͉ innate immunity

The first WHO International Standard and International Reference Panel for anti-SARS-CoV-2 immunoglobulin were established by the WHO Expert Committee on Biological Standardization in December, 2020. The WHO International Antibody Standards are intended to serve as global reference reagents, against which national reference preparations or secondary standards can be calibrated. Calibration will facilitate comparison of results of assays (eg, of the neutralising antibody response to candidate COVID-19 vaccines) conducted in different countries. Use of these standards is expected to contribute to better understanding of the immune response, and particularly of the correlates of protection. This Personal View provides some technical details of the WHO Antibody Standards for SARS-CoV-2, focusing specifically on the use of these standards for the evaluation of the immune response to COVID-19 vaccines, rather than other applications (eg, diagnostic or therapeutic). The explanation with regard to why rapid adoption of the standards is crucial is also included, as well as how funders, journals, regulators, and ethics committees could drive adoption in the interest of public health.

(MP). Data Availability. The cryo-EM maps and the refined atomic model of DmSERINC were deposited in the EMDB and wwPDB, respectively, with accession codes EMD-10277 and EMD-10279 and PDB 6SP2. Source data for Figures 4a, 4b, 4c, 4e and for Extended Data Figures 1a, 1c, 1d, 1e, 2b, 3b, 4g-i, 6e-g, are available with the paper online. Author Contributions V.E.P. expressed, purified and characterised DmSERINC, built the atomic model, developed and conducted thermostability assays; V.E.P., P.C., and A.B.-C. prepared and screened cryo-EM grids; A.N. collected all cryo-EM data; V.E.P. and P.C. refined the DmSERINC structure; A.R. and P.C. generated stable cell line for SERINC5 expression, purified and characterised SERINC5 and determined the structure; A.R. conducted thermostability assays on SERINC5 and purified the Fab; P.C. produced mutant SERINC5 constructs; M.P. and C.B. developed and performed assays to measure surface exposure, restriction activity and virion incorporation of SERINC5 variants; W.

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