The calibration of WHO international standards using SARS-CoV-2 ancestral multiplex sVNT was modelled (Extended Data Fig. 25) and found that the neutralization titres were reduced from ancestral SARS-CoV-2 in the following order for the human SARS-CoV-2 variants (from least to most): Alpha, Delta, Delta plus, Lambda, Gamma, Beta, Mu, Omicron BA.2 and Omicron BA.1 (Extended Data Fig. We first tested the 20-plex sVNT using the WHO international standard 20/136 (ref.

1a–d.Īll RBDs bind to human ACE2 in a dose-dependent manner in the multiplex Luminex system (Extended Data Fig.

The phylogenetic relatedness and the amino acid sequence differences of these RBDs and spikes are shown in Extended Data Fig. For clade-1a, we included human SARS-CoV-1 and bat sarbecoviruses (Rs2018B, LYRa11, RsSHC014 and WIV1). Clade-1b viruses included the ancestral SARS-CoV-2 virus (Wuhan-hu-1), variants of concern or interest (Alpha, Delta, Beta, Gamma, Delta plus, Lambda, Mu, Omicron BA.1 and Omicron BA.2) and animal sarbecoviruses (BANAL-52, BANAL-236, GD-1, RaTG13 and GX-P5L). We applied our SARS-CoV-2 surrogate virus neutralization test (sVNT) platform 23, 24 which can detect total immunodominant neutralizing antibodies targeting the viral spike (S), and differentiated antibody responses to several human and animal sarbecoviruses in a 20-plex assay that included 15 receptor binding domains (RBDs) of the SARS-CoV-2 clade (clade-1b) viruses and 5 RBDs of the SARS-CoV-1 clade (clade-1a) viruses. SARS-CoV-2 Omicron, which contains 32 amino acid mutations in the spike, was first detected in South Africa and Botswana and has rapidly spread to many countries 19, 20, 21, 22. SARS-CoV-2 VOCs have either developed resistance/escape to neutralizing antibodies 11, 12, 13, 14, 15, 16 or acquired mutations that have increased transmission or pathogenicity 17, 18. So far, five major VOCs have been recognized by the WHO (Alpha, Beta, Gamma, Delta and Omicron). SARS-CoV-2 variants of concern (VOC) have emerged since late 2020, probably in response to immune responses in the human population 10.

Multiple sarbecoviruses have been detected in bats 5, 6, 7, 8 and, more recently, in pangolins 9. Bats are reservoirs for SARS-related coronaviruses 3, 4. 1), which causes COVID-19, is a member of the subgenus Sarbecovirus, as is SARS-CoV-1, which caused the SARS epidemic 19 years ago 2. The coronavirus disease 2019 (COVID-19) pandemic started in December 2019 and has caused 591 million cases and claimed 6.4 million lives as of 19 August 2022. SARS-CoV-2 Omicron variant emerged under immune selection

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