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

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.

A number of linear and conformation-dependent neutralizing monoclonal antibodies (MAbs) have been mapped to the first and second variable (Vi and V2) domains of human immunodeficiency virus type 1 (HIV-1) gp120. The majority of these MAbs are as effective at neutralizing HIV-i infectivity as MAbs to the V3 domain and the CD4 binding site. The linear MAbs bind to amino acid residues 162 to 171, and changes at residues 183/184 (PI/SG) and 191/192/193 (YSVGSS) within the V2 domain abrogate the binding of the two conformation-dependent MAbs, 11/68b and CRA-4, respectively. Surprisingly, a change at residue 435 (Y/H or Y/S), in a region of gpl20 near the CD4 binding site (M.

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Vaccination with live attenuated simian immunodeficiency virus (SIVmacC8) confers potent, reproducible protection against homologous wild-type virus challenge (SIVmacJ5). The ability of SIVmacC8 to confer resistance to superinfection with an uncloned ex vivo derivative of SIVmac251 (SIVmac32H/L28) was investigated. In naïve, Mauritian-derived cynomolgus macaques (Macaca fascicularis), SIVmac32H/L28 replicated to high peak titres (.10 8 SIV RNA copies ml), persisted at high levels and induced distinctive pathology in lymphoid tissues. In cynomolgus macaques vaccinated with SIVmacC8, no evidence of detectable superinfection was observed in 3/8 vaccinates following challenge 3 or 20 weeks later with SIVmac32H/L28. Analyses after SIVmac32H/L28 challenge revealed a significant reduction in viral RNA (P,0.001) and DNA levels between 20 week vaccinates and challenge controls. Amongst 3 week vaccinates, less potent protection was observed. However, analysis of env from breakthrough virus indicated .99 % sequence similarity with the vaccine virus. Highly sensitive PCR assays that distinguish vaccine and challenge virus stocks demonstrated restimulation of replication of the vaccine virus SIVmacC8 in the face of potent protection against a vigorous, homologous challenge virus. Vaccine-induced antiviral neutralizing antibodies and anti-Nef CD8 + cytotoxic T cell responses did not correlate with the outcome of the challenge. Defining the mechanism of vaccine protection will need to account for the effective control of a genetically closely related challenge virus whilst remaining unable to suppress replication of the pre-existing vaccine virus. The role of innate and intrinsic anti-retroviral immunity in the protection conferred by live attenuated SIV vaccines warrants careful study.