mRNA-1273 and BNT162b2 mRNA vaccines have reduced neutralizing activity against the SARS-CoV-2 Omicron variant

Edara, Venkata Viswanadh; Manning, Kelly; Ellis, Madison; Lai, Lilin; Moore, Kathryn M.; Foster, Stephanie L.; Floyd, Katharine; Davis-Gardner, Meredith E.; Mantus, Grace; Nyhoff, Lindsay E.; Bechnack, Sarah; Alaaeddine, Ghina; Naji, Amal; Samaha, Hady; Lee, Matthew; Bristow, Laurel; Hussaini, Laila; Ciric, Caroline; Nguyen, Phuong-Vi; Gagné, Matthew; Roberts-Torres, Jesmine; Henry, Amy R.; Godbole, Sucheta; Grakoui, Arash; Sexton, Marybeth; Piantadosi, Anne; Waggoner, Jesse J.; Douek, Daniel C.; Anderson, Evan J.; Rouphael, Nadine; Wrammert, Jens; Suthar, Mehul S.

doi:10.1101/2021.12.20.473557

Cited by 43 publications

(26 citation statements)

References 9 publications

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“…It was shown, that sera from vaccinated individuals with 2 doses BNT162b2 or mRNA-1273 has 22-30-fold decrease in neutralizing activity against the Omicron variant compared with wild type virus [3][4]. A similar decrease in neutralizing activity was shown in other study comparing two vaccines: ChAdOx1-nCoV-19 and BNT162b2 [4][5].…”

Section: Introductionsupporting

confidence: 62%

Retention of Neutralizing response against SARS-CoV-2 Omicron variant in Sputnik V vaccinated individuals

Lapa

Grousova

Matusali

et al. 2022

Preprint

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The new variant Omicron (B.1.1.529) of SARS-CoV-2, first identified in November 2021, is rapidly spreading all around the world. The Omicron becomes the dominant variant of SARS-CoV-2. There are many ongoing studies evaluating the effectiveness of existing vaccines. Studies on neutralizing activity of vaccinated sera against Omicron variant are currently being carried out in many laboratories. In this study, we have shown the neutralizing activity of sera against SARS-CoV-2 Omicron (B.1.1.529) variant compared to the reference Wuhan D614G (B.1) variant in individuals vaccinated with 2 doses of Sputnik V or BNT162b2 in different time points up to 6 months after vaccination. We performed analysis on sample pools with comparable NtAb to Wuhan D614G variant. The decrease in neutralizing antibody (NtAb) to the Omicron variant was 8.1 folds for group of Sputnik V-vaccinated and 21.4 folds for group of BNT162b2-vaccinated. Analysis showed that 74.2% of Sputnik V- and 56.9% of BNT162b2-vaccinated sera had detectable NtAb to SARS-CoV-2 Omicron variant. The decrease in NtAb to SARS-CoV-2 Omicron variant compared to Wuhan variant has been shown for many COVID-19 vaccines in use, with some showing no neutralization at all. Today the necessity of third booster vaccination is obvious. And the most effective approach, already shown in several studies, is the use of heterologous booster vaccination pioneered in COVID-19 vaccines by Sputnik V.

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Section: Introductionsupporting

confidence: 62%

Retention of Neutralizing response against SARS-CoV-2 Omicron variant in Sputnik V vaccinated individuals

Lapa

Grousova

Matusali

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…Preliminary reports suggest that the Omicron variant is highly transmissible, even in fully vaccinated individuals and individuals that received a booster dose [3][4][5] . These results are congruous with recent findings that the Omicron variant is markedly resistant to neutralization by sera not only from convalescent patients, but also from individuals vaccinated with many widely used COVID-19 vaccines [6][7][8][9][10][11] . In addition, the neutralization capacity of monoclonal antibodies (mAbs) in clinical use against COVID-19 is abolished or severely impaired against the Omicron variant [12][13][14] .…”

Section: Main Textsupporting

confidence: 81%

“…SARS-CoV-2 Omicron that emerged in November 2021 disseminates quickly and may replace Delta as the dominant circulating SARS-CoV-2 variant. Current reports from epidemiology and experimental studies suggest that the Omicron variant can efficiently infect individuals after twodose of vaccination or even after receiving the third booster dose, due to its strong capacity of evading antibody neutralization [6][7][8][9][10][11] . Additional reports have demonstrated that the neutralization capacity of therapeutic monoclonal antibodies against the Omicron variant are also severely impaired, including some with completely abolished activity [12][13][14] .…”

Section: Discussionmentioning

confidence: 99%

“…A large body of timely reports has revealed that the Omicron variant can robustly escape from neutralization antibodies, allowing it to infect fully vaccinated or even booster vaccinated individuals 3,4,[6][7][8][9][10][11][12][13][14] . Our results in this study suggest that the virus replication fitness of the Omicron variant is severely compromised as a trade-off of escaping from neutralization antibodies.…”

Section: Discussionmentioning

confidence: 99%

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Attenuated replication and pathogenesis of SARS-CoV-2 B.1.1.529 Omicron

Yuen

Shuai

Chan

et al. 2021

Preprint

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SARS-CoV-2 Omicron emerged in November 2021 and is rapidly spreading among the human populations. The variant contains 34 changes in its spike protein including 15 substitutions at the receptor-binding domain (RBD). While recent reports reveal that the Omicron variant can robustly escape from vaccine and therapeutic neutralization antibodies, the pathogenicity of the virus remains unknown. Here, we investigate the virological features and pathogenesis of the Omicron variant using in vitro and in vivo models. Our results demonstrate that the replication of the Omicron variant is dramatically attenuated in Calu3 and Caco2 but not in VeroE6 cells. Further mechanistic investigations reveal that the Omicron variant is deficient in transmembrane serine protease 2 (TMPRSS2) usage in comparison to that of WT, Alpha, Beta, and Delta variant, which explained its inefficient replication in Calu3 and Caco2 cells. Importantly, the replication of the Omicron variant is markedly attenuated in both the upper and lower respiratory tract of infected K18-hACE2 mice in comparison to that of WT and Delta variant, which results in its dramatically ameliorated lung pathology. When compared with SARS-CoV-2 WT, Alpha, Beta, and Delta variant, infection by the Omicron variant causes the least body weight loss and mortality rate. Overall, our study demonstrates that the Omicron variant is significantly attenuated in virus replication and pathogenicity in comparison with WT and previous variants. Our data suggest the current global vaccination strategy has forced SARS-CoV-2 into a new evolutionary trajectory towards reduced replication fitness in exchange of better immune escape. These findings are critical for setting policy in the pandemic control and disease management of COVID-19.

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“…The COVID-19 pandemic, resulting from the zoonotic infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to rage on, fueled by continuously evolving variants, which are making current licensed vaccines less effective (Araf et al, 2022;Doria-Rose et al, 2021;Edara et al, 2021;Garcia-Beltran et al, 2022;Liu et al, 2021). Vaccines capable of neutralizing all SARS-CoV-2 variants for the foreseeable future are of high interest.…”

Section: Introductionmentioning

confidence: 99%

Vaccine-elicited murine antibody WS6 neutralizes diverse beta-coronaviruses by recognizing a helical stem supersite of vulnerability

Shi

Wang

Zhou

et al. 2022

Preprint

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Immunization with SARS-CoV-2 spike elicits diverse antibodies, but can any of these neutralize broadly? Here, we report the isolation and characterization of antibody WS6, from a mouse immunized with mRNA encoding the SARS-CoV-2 spike. WS6 bound diverse beta-coronavirus spikes and neutralized SARS-CoV-2 variants, SARS-CoV, and related sarbecoviruses. Epitope mapping revealed WS6 to target a region in the S2 subunit, which was conserved among SARS-CoV-2, MERS-CoV, and hCoV-OC43. The crystal structure at 2-angstrom resolution of WS6 with its S2 epitope revealed recognition to center on a conserved helix, which was occluded in both prefusion and post-fusion spike conformations. Structural and neutralization analyses indicated WS6 to neutralize by inhibiting fusion, post-viral attachment. Comparison of WS6 to other antibodies recently identified from convalescent donors or mice immunized with diverse spikes indicated a stem-helical supersite - centered on hydrophobic residues Phe1148, Leu1152, Tyr1155, and Phe1156 - to be a promising target for vaccine design.

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mRNA-1273 and BNT162b2 mRNA vaccines have reduced neutralizing activity against the SARS-CoV-2 Omicron variant

Cited by 43 publications

References 9 publications

Retention of Neutralizing response against SARS-CoV-2 Omicron variant in Sputnik V vaccinated individuals

Retention of Neutralizing response against SARS-CoV-2 Omicron variant in Sputnik V vaccinated individuals

Attenuated replication and pathogenesis of SARS-CoV-2 B.1.1.529 Omicron

Vaccine-elicited murine antibody WS6 neutralizes diverse beta-coronaviruses by recognizing a helical stem supersite of vulnerability

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