Activity of convalescent and vaccine serum against SARS-CoV-2 Omicron.

The Omicron (B.1.1.529) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was initially identified in November 2021 in South Africa and Botswana, as well as in a sample from a traveller from South Africa in Hong Kong1,2. Since then, Omicron has been detected globally. This variant appears to be at least as infectious as Delta (B.1.617.2), has already caused superspreader events3, and has outcompeted Delta within weeks in several countries and metropolitan areas. Omicron hosts an unprecedented number of mutations in its spike gene and early reports have provided evidence for extensive immune escape and reduced vaccine effectiveness2,4-6. Here we investigated the virus-neutralizing and spike protein-binding activity of sera from convalescent, double mRNA-vaccinated, mRNA-boosted, convalescent double-vaccinated and convalescent boosted individuals against wild-type, Beta (B.1.351) and Omicron SARS-CoV-2 isolates and spike proteins. Neutralizing activity of sera from convalescent and double-vaccinated participants was undetectable or very low against Omicron compared with the wild-type virus, whereas neutralizing activity of sera from individuals who had been exposed to spike three or four times through infection and vaccination was maintained, although at significantly reduced levels. Binding to the receptor-binding and N-terminal domains of the Omicron spike protein was reduced compared with binding to the wild type in convalescent unvaccinated individuals, but was mostly retained in vaccinated individuals.

Carreño JM ，Alshammary H ，Tcheou J ，Singh G ，Raskin AJ ，Kawabata H ，Sominsky LA ，Clark JJ ，Adelsberg DC ，Bielak DA ，Gonzalez-Reiche AS ，Dambrauskas N ，Vigdorovich V ，PSP-PARIS Study Group ，Srivastava K ，Sather DN ，Sordillo EM ，Bajic G ，van Bakel H ，Simon V ，Krammer F ... -  《-》

Considerable escape of SARS-CoV-2 Omicron to antibody neutralization.

The SARS-CoV-2 Omicron variant was first identified in November 2021 in Botswana and South Africa1-3. It has since spread to many countries and is expected to rapidly become dominant worldwide. The lineage is characterized by the presence of around 32 mutations in spike-located mostly in the N-terminal domain and the receptor-binding domain-that may enhance viral fitness and enable antibody evasion. Here we isolated an infectious Omicron virus in Belgium from a traveller returning from Egypt. We examined its sensitivity to nine monoclonal antibodies that have been clinically approved or are in development4, and to antibodies present in 115 serum samples from COVID-19 vaccine recipients or individuals who have recovered from COVID-19. Omicron was completely or partially resistant to neutralization by all monoclonal antibodies tested. Sera from recipients of the Pfizer or AstraZeneca vaccine, sampled five months after complete vaccination, barely inhibited Omicron. Sera from COVID-19-convalescent patients collected 6 or 12 months after symptoms displayed low or no neutralizing activity against Omicron. Administration of a booster Pfizer dose as well as vaccination of previously infected individuals generated an anti-Omicron neutralizing response, with titres 6-fold to 23-fold lower against Omicron compared with those against Delta. Thus, Omicron escapes most therapeutic monoclonal antibodies and, to a large extent, vaccine-elicited antibodies. However, Omicron is neutralized by antibodies generated by a booster vaccine dose.

Planas D ，Saunders N ，Maes P ，Guivel-Benhassine F ，Planchais C ，Buchrieser J ，Bolland WH ，Porrot F ，Staropoli I ，Lemoine F ，Péré H ，Veyer D ，Puech J ，Rodary J ，Baele G ，Dellicour S ，Raymenants J ，Gorissen S ，Geenen C ，Vanmechelen B ，Wawina-Bokalanga T ，Martí-Carreras J ，Cuypers L ，Sève A ，Hocqueloux L ，Prazuck T ，Rey FA ，Simon-Loriere E ，Bruel T ，Mouquet H ，André E ，Schwartz O ... -  《-》

Striking antibody evasion manifested by the Omicron variant of SARS-CoV-2.

The B.1.1.529/Omicron variant of SARS-CoV-2 was only recently detected in southern Africa, but its subsequent spread has been extensive, both regionally and globally1. It is expected to become dominant in the coming weeks2, probably due to enhanced transmissibility. A striking feature of this variant is the large number of spike mutations3 that pose a threat to the efficacy of current COVID-19 vaccines and antibody therapies4. This concern is amplified by the findings of our study. Here we found that B.1.1.529 is markedly resistant to neutralization by serum not only from patients who recovered from COVID-19, but also from individuals who were vaccinated with one of the four widely used COVID-19 vaccines. Even serum from individuals who were vaccinated and received a booster dose of mRNA-based vaccines exhibited substantially diminished neutralizing activity against B.1.1.529. By evaluating a panel of monoclonal antibodies against all known epitope clusters on the spike protein, we noted that the activity of 17 out of the 19 antibodies tested were either abolished or impaired, including ones that are currently authorized or approved for use in patients. Moreover, we also identified four new spike mutations (S371L, N440K, G446S and Q493R) that confer greater antibody resistance on B.1.1.529. The Omicron variant presents a serious threat to many existing COVID-19 vaccines and therapies, compelling the development of new interventions that anticipate the evolutionary trajectory of SARS-CoV-2.

Liu L ，Iketani S ，Guo Y ，Chan JF ，Wang M ，Liu L ，Luo Y ，Chu H ，Huang Y ，Nair MS ，Yu J ，Chik KK ，Yuen TT ，Yoon C ，To KK ，Chen H ，Yin MT ，Sobieszczyk ME ，Huang Y ，Wang HH ，Sheng Z ，Yuen KY ，Ho DD ... -  《-》

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

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) omicron variant emerged in November 2021 and consists of several mutations within the spike. We use serum from mRNA-vaccinated individuals to measure neutralization activity against omicron in a live-virus assay. At 2-4 weeks after a primary series of vaccinations, we observe a 30-fold reduction in neutralizing activity against omicron. Six months after the initial two-vaccine doses, sera from naive vaccinated subjects show no neutralizing activity against omicron. In contrast, COVID-19-recovered individuals 6 months after receiving the primary series of vaccinations show a 22-fold reduction, with the majority of the subjects retaining neutralizing antibody responses. In naive individuals following a booster shot (third dose), we observe a 14-fold reduction in neutralizing activity against omicron, and over 90% of subjects show neutralizing activity. These findings show that a third dose is required to provide robust neutralizing antibody responses against the omicron variant.

Edara VV ，Manning KE ，Ellis M ，Lai L ，Moore KM ，Foster SL ，Floyd K ，Davis-Gardner ME ，Mantus G ，Nyhoff LE ，Bechnak S ，Alaaeddine G ，Naji A ，Samaha H ，Lee M ，Bristow L ，Gagne M ，Roberts-Torres J ，Henry AR ，Godbole S ，Grakoui A ，Saxton M ，Piantadosi A ，Waggoner JJ ，Douek DC ，Rouphael N ，Wrammert J ，Suthar MS ... -  《-》

Antibody resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7.

Wang P ，Nair MS ，Liu L ，Iketani S ，Luo Y ，Guo Y ，Wang M ，Yu J ，Zhang B ，Kwong PD ，Graham BS ，Mascola JR ，Chang JY ，Yin MT ，Sobieszczyk M ，Kyratsous CA ，Shapiro L ，Sheng Z ，Huang Y ，Ho DD ... -  《-》