Omicron extensively but incompletely escapes Pfizer BNT162b2 neutralization

Cele, Sandile; Jackson, Laurelle; Khoury, David S.; Khan, Khadija; Moyo-Gwete, Thandeka; Tegally, Houriiyah; San, James Emmanuel; Cromer, Deborah; Scheepers, Cathrine; Amoako, Daniel G.; Karim, Farina; Bernstein, Mallory; Lustig, Gila; Archary, Derseree; Smith, Muneerah; Ganga, Yashica; Jule, Zesuliwe; Reedoy, Kajal; Hwa, Shi-Hsia; Giandhari, Jennifer; Blackburn, Jonathan M.; Gosnell, Bernadett I.; Karim, Salim S. Abdool; Hanekom, Willem A.; in, Network for Genomic Surveillance; Team, Commit-Kzn; Gottberg, Anne von; Bhiman, Jinal N.; Lessells, Richard; Moosa, Mahomed-Yunus S.; Davenport, Miles P.; Oliveira, Túlio de; Moore, Penny L.; Sigal, Alex

doi:10.1038/d41586-021-03824-5

Cited by 204 publications

(201 citation statements)

References 21 publications

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“…We isolated Omicron virus without the R346K mutation from an infection in South Africa. This virus had similar neutralization escape (Fig S1 ) as a previous Omicron isolate with the R346K mutation 1 . We neutralized this isolate with plasma from the blood of 15 participants enrolled during the Omicron infection wave in South Africa, with each participant having a confirmed diagnosis of SARS-CoV-2 by qPCR.…”

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confidence: 54%

“…(https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/fil e/1043807/technical-briefing-33.pdf). In South Africa Omicron infections led to a lower incidence of severe disease relative to other variants 8 , although this can be at least partly explained by pre-existing immunity 1 . While Omicron infections are rising steeply, many countries still have high levels of infection with the Delta variant.…”

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confidence: 96%

“…The Omicron variant of SARS-CoV-2, first identified in November 2021 in South Africa and Botswana, has been shown by us 1 and others [2][3][4][5][6][7] to have extensive but incomplete escape from immunity elicited by vaccines and previous infection, with boosted is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint…”

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confidence: 99%

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Omicron infection of vaccinated individuals enhances neutralizing immunity against the Delta variant

Khan

Karim

Cele

et al. 2021

Preprint

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Omicron has been shown to be highly transmissible and have extensive evasion of neutralizing antibody immunity elicited by vaccination and previous SARS-CoV-2 infection. Omicron infections are rapidly expanding worldwide often in the face of high levels of Delta infections. Here we characterized developing immunity to Omicron and investigated whether neutralizing immunity elicited by Omicron also enhances neutralizing immunity of the Delta variant. We enrolled both previously vaccinated and unvaccinated individuals who were infected with SARS-CoV-2 in the Omicron infection wave in South Africa soon after symptom onset. We then measured their ability to neutralize both Omicron and Delta virus at enrollment versus a median of 14 days after enrollment. Neutralization of Omicron increased 14-fold over this time, showing a developing antibody response to the variant. Importantly, there was an enhancement of Delta virus neutralization, which increased 4.4-fold. The increase in Delta variant neutralization in individuals infected with Omicron may result in decreased ability of Delta to re-infect those individuals. Along with emerging data indicating that Omicron, at this time in the pandemic, is less pathogenic than Delta, such an outcome may have positive implications in terms of decreasing the Covid-19 burden of severe disease.

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confidence: 54%

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confidence: 96%

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Omicron infection of vaccinated individuals enhances neutralizing immunity against the Delta variant

Khan

Karim

Cele

et al. 2021

Preprint

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“…While for Delta S trimer, our recent work showed the open-transition ratio is 75.3%-24.7%, indicating the conformational masking mechanism may be less effective for the Delta variant 32,36 . This could contribute greatly to the striking immune evasion of the Omicron variant 15,[17][18][19][20][21][22] .…”

Section: Discussionmentioning

confidence: 99%

“…Recently, a new variant, named Omicron (B.1.1.529), was first reported in South Africa in November 2021 and classified as the fifth VOC by the World Health Organization (WHO) on 26 November 2021. Omicron exhibits a high transmission rate (R0>3) 12,13 , and, as of 22 December 2021, it has spread into 110 countries 14 .…”

Section: Introductionmentioning

confidence: 99%

Molecular basis of SARS-CoV-2 Omicron variant receptor engagement and antibody evasion and neutralization

Qin

Han

et al. 2022

Preprint

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The SARS-CoV-2 Omicron variant exhibits striking immune evasion and is spreading globally at an unprecedented speed. Understanding the underlying structural basis of the high transmissibility and greatly enhanced immune evasion of Omicron is of high importance. Here through cryo-EM analysis, we present both the closed and open states of the Omicron spike, which appear more compact than the counterparts of the G614 strain, potentially related to the Omicron substitution induced enhanced protomer-protomer and S1-S2 interactions. The closed state showing dominant population may indicate a conformational masking mechanism of immune evasion for Omicron spike. Moreover, we capture two states for the Omicron S/ACE2 complex with S binding one or two ACE2s, revealing that the substitutions on the Omicron RBM result in new salt bridges/H-bonds and more favorable electrostatic surface properties, together strengthened interaction with ACE2, in line with the higher ACE2 affinity of the Omicron relative to the G614 strain. Furthermore, we determine cryo-EM structures of the Omicron S/S3H3 Fab, an antibody able to cross-neutralize major variants of concern including Omicron, elucidating the structural basis for S3H3-mediated broad-spectrum neutralization. Our findings shed new lights on the high transmissibility and immune evasion of the Omicron variant and may also inform design of broadly effective vaccines against emerging variants.

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Association Between 3 Doses of mRNA COVID-19 Vaccine and Symptomatic Infection Caused by the SARS-CoV-2 Omicron and Delta Variants

Accorsi

Britton

Fleming-Dutra

et al. 2022

JAMA

580

562

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IMPORTANCEAssessing COVID-19 vaccine performance against the rapidly spreading SARS-CoV-2 Omicron variant is critical to inform public health guidance.OBJECTIVE To estimate the association between receipt of 3 doses of Pfizer-BioNTech BNT162b2 or Moderna mRNA-1273 vaccine and symptomatic SARS-CoV-2 infection, stratified by variant (Omicron and Delta). DESIGN, SETTING, AND PARTICIPANTSA test-negative case-control analysis among adults 18 years or older with COVID-like illness tested December 10, 2021, through January 1, 2022, by a national pharmacy-based testing program (4666 COVID-19 testing sites across 49 US states).EXPOSURES Three doses of mRNA COVID-19 vaccine (third dose Ն14 days before test and Ն6 months after second dose) vs unvaccinated and vs 2 doses 6 months or more before test (ie, eligible for a booster dose). MAIN OUTCOMES AND MEASURESAssociation between symptomatic SARS-CoV-2 infection (stratified by Omicron or Delta variants defined using S-gene target failure) and vaccination (3 doses vs unvaccinated and 3 doses vs 2 doses). Associations were measured with multivariable multinomial regression. Among cases, a secondary outcome was median cycle threshold values (inversely proportional to the amount of target nucleic acid present) for 3 viral genes, stratified by variant and vaccination status.RESULTS Overall, 23 391 cases (13 098 Omicron; 10 293 Delta) and 46 764 controls were included (mean age, 40.3 [SD, 15.6] years; 42 050 [60.1%] women). Prior receipt of 3 mRNA vaccine doses was reported for 18.6% (n = 2441) of Omicron cases, 6.6% (n = 679) of Delta cases, and 39.7% (n = 18 587) of controls; prior receipt of 2 mRNA vaccine doses was reported for 55.3% (n = 7245), 44.4% (n = 4570), and 41.6% (n = 19 456), respectively; and being unvaccinated was reported for 26.0% (n = 3412), 49.0% (n = 5044), and 18.6% (n = 8721), respectively. The adjusted odds ratio for 3 doses vs unvaccinated was 0.33 (95% CI, 0.31-0.35) for Omicron and 0.065 (95% CI, 0.059-0.071) for Delta; for 3 vaccine doses vs 2 doses the adjusted odds ratio was 0.34 (95% CI, 0.32-0.36) for Omicron and 0.16 (95% CI, 0.14-0.17) for Delta. Median cycle threshold values were significantly higher in cases with 3 doses vs 2 doses for both Omicron and Delta (

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Omicron extensively but incompletely escapes Pfizer BNT162b2 neutralization

Cited by 204 publications

References 21 publications

Omicron infection of vaccinated individuals enhances neutralizing immunity against the Delta variant

Omicron infection of vaccinated individuals enhances neutralizing immunity against the Delta variant

Molecular basis of SARS-CoV-2 Omicron variant receptor engagement and antibody evasion and neutralization

Association Between 3 Doses of mRNA COVID-19 Vaccine and Symptomatic Infection Caused by the SARS-CoV-2 Omicron and Delta Variants

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