Lu Lu1, Bobo Wing Yee Mok1, Lin Lei Chen1, Jacky Man Chun Chan2, Owen Tak Yin Tsang2, Bosco Hoi Shiu Lam3, Vivien Wai Man Chuang4, Allen Wing Ho Chu1, Wan Mui Chan1, Jonathan Daniel Ip1, Brian Pui Chun Chan1, Ruiqi Zhang5, Cyril Chik Yan Yip1,6, Vincent Chi Chung Cheng1,6, Kwok Hung Chan1, Dong Yan Jin7, Ivan Fan Ngai Hung5, Kwok Yung Yuen1,6, Honglin Chen1, Kelvin Kai Wang To1,6. 1. State Key Laboratory for Emerging Infectious Diseases, Carol Yu Centre for Infection, Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China. 2. Department of Medicine and Geriatrics, Princess Margaret Hospital, Hong Kong Special Administrative Region, People's Republic of China. 3. Department of Pathology, Princess Margaret Hospital, Hong Kong Special Administrative Region, People's Republic of China. 4. Quality & Safety Division, Hospital Authority, Hong Kong Special Administrative Region, People's Republic of China. 5. Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China. 6. Department of Microbiology, Queen Mary Hospital, Hong Kong Special Administrative Region, People's Republic of Chinaand. 7. School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, People's Republic of China.
Abstract
BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) omicron variant, designated as a variant of concern by the World Health Organization, carries numerous spike mutations that are known to evade neutralizing antibodies elicited by coronavirus disease 2019 (COVID-19) vaccines. A deeper understanding of the susceptibility of omicron variant to vaccine-induced neutralizing antibodies is urgently needed for risk assessment. METHODS: Omicron variant strains HKU691 and HKU344-R346K were isolated from patients using TMPRSS2-overexpressing VeroE6 cells. Whole genome sequence was determined using nanopore sequencing. Neutralization susceptibility of ancestral lineage A virus and the omicron, delta and beta variants to sera from 25 BNT162b2 and 25 CoronaVac vaccine recipients was determined using a live virus microneutralization assay. RESULTS: The omicron variant strain HKU344-R346K has an additional spike R346K mutation, which is present in 8.5% of strains deposited in the GISAID database. Only 20% and 24% of BNT162b2 recipients had detectable neutralizing antibody against the omicron variant HKU691 and HKU344-R346K, respectively, whereas none of the CoronaVac recipients had detectable neutralizing antibody titer against either omicron isolate. For BNT162b2 recipients, the geometric mean neutralization antibody titers (GMTs) of the omicron variant isolates (5.43 and 6.42) were 35.7-39.9-fold lower than that of the ancestral virus (229.4), and the GMTs of both omicron variant isolates were significantly lower than those of the beta and delta variants. There was no significant difference in the GMTs between HKU691 and HKU344-R346K. CONCLUSIONS: Omicron variant escapes neutralizing antibodies elicited by BNT162b2 or CoronaVac. The additional R346K mutation did not affect the neutralization susceptibility. Our data suggest that the omicron variant may be associated with lower COVID-19 vaccine effectiveness.
BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) omicron variant, designated as a variant of concern by the World Health Organization, carries numerous spike mutations that are known to evade neutralizing antibodies elicited by coronavirus disease 2019 (COVID-19) vaccines. A deeper understanding of the susceptibility of omicron variant to vaccine-induced neutralizing antibodies is urgently needed for risk assessment. METHODS: Omicron variant strains HKU691 and HKU344-R346K were isolated from patients using TMPRSS2-overexpressing VeroE6 cells. Whole genome sequence was determined using nanopore sequencing. Neutralization susceptibility of ancestral lineage A virus and the omicron, delta and beta variants to sera from 25 BNT162b2 and 25 CoronaVac vaccine recipients was determined using a live virus microneutralization assay. RESULTS: The omicron variant strain HKU344-R346K has an additional spike R346K mutation, which is present in 8.5% of strains deposited in the GISAID database. Only 20% and 24% of BNT162b2 recipients had detectable neutralizing antibody against the omicron variant HKU691 and HKU344-R346K, respectively, whereas none of the CoronaVac recipients had detectable neutralizing antibody titer against either omicron isolate. For BNT162b2 recipients, the geometric mean neutralization antibody titers (GMTs) of the omicron variant isolates (5.43 and 6.42) were 35.7-39.9-fold lower than that of the ancestral virus (229.4), and the GMTs of both omicron variant isolates were significantly lower than those of the beta and delta variants. There was no significant difference in the GMTs between HKU691 and HKU344-R346K. CONCLUSIONS: Omicron variant escapes neutralizing antibodies elicited by BNT162b2 or CoronaVac. The additional R346K mutation did not affect the neutralization susceptibility. Our data suggest that the omicron variant may be associated with lower COVID-19 vaccine effectiveness.
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Authors: Caroline G Atyeo; Lydia L Shook; Sara Brigida; Rose M De Guzman; Stepan Demidkin; Cordelia Muir; Babatunde Akinwunmi; Arantxa Medina Baez; Maegan L Sheehan; Erin McSweeney; Madeleine D Burns; Ruhi Nayak; Maya K Kumar; Chinmay D Patel; Allison Fialkowski; Dana Cvrk; Ilona T Goldfarb; Lael M Yonker; Alessio Fasano; Alejandro B Balazs; Michal A Elovitz; Kathryn J Gray; Galit Alter; Andrea G Edlow Journal: Nat Commun Date: 2022-06-28 Impact factor: 17.694