Increased resistance of SARS-CoV-2 Omicron variant to neutralization by vaccine-elicited and therapeutic antibodies

Tada, Takuya; Zhou, Hao; Dcosta, Belinda M; Samanovic, Marie I.; Chivukula, Vidya; Herati, Ramin S.; Hubbard, Stevan R.; Mulligan, Mark J.; Landau, Nathaniel R.

doi:10.1016/j.ebiom.2022.103944

Cited by 128 publications

(117 citation statements)

References 43 publications

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“…In fact, this may be also another reason for the slowdown registered in most countries regarding to the third dose. Although new studies have suggested that COVID-19 vaccines are slightly less effective against new variants, COVID-19 vaccines still appear to provide protection against severe COVID-19 [ 24 , 25 , 26 ].…”

Section: Discussionmentioning

confidence: 99%

Citizen Stance towards Mandatory COVID-19 Vaccination and Vaccine Booster Doses: A Study in Colombia, El Salvador and Spain

et al. 2022

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The infections and deaths resulting from Coronavirus Disease 2019 (COVID-19) triggered the need for some governments to make COVID-19 vaccines mandatory. The present study aims to analyze the position of 3026 adults in Colombia, El Salvador, and Spain regarding the possibility of making COVID-19 vaccine mandatory and the intention to be vaccinated with the booster or possible successive doses. Data from an online survey conducted from August to December 2021 among a non-representative sample of Spanish-speaking countries were collected. Multinomial Logistic Regression Models were used. A total of 77.4% of Colombians were in favor of mandatory vaccination compared to 71.5% of Salvadorians and 65.4% of Spaniards (p < 0.000). Women and people over 65 years of age were the groups most in favor of making the vaccine mandatory (p < 0.000). A total of 79.4% said they had received a third dose or would intend to receive the third dose or future doses, if necessary, compared with 9.4% who expressed doubts and 9.9% who refused to be vaccinated or did not intend to be vaccinated. Among the measures that could be taken to motivate vaccination, 63.0% and 60.6% were in favor of requiring a negative test to enter any place of leisure or work, respectively, compared to 16.2% in favor of suspension from work without pay. The acceptance of mandatory vaccination and of third or future doses varies greatly according to sociodemographic characteristics and work environment. As such, it is recommended that policy makers adapt public health strategies accordingly.

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Section: Discussionmentioning

confidence: 99%

Citizen Stance towards Mandatory COVID-19 Vaccination and Vaccine Booster Doses: A Study in Colombia, El Salvador and Spain

et al. 2022

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“…After 1 day, virus-containing supernatants were harvested and passed through a 0.45 µm filter. The filtered supernatant was concentrated by ultracentrifugation at 30,000× g for 90 min at 4 • C. The viruses were resuspended in DMEM containing 10% FBS and normalized for reverse transcriptase (RT) activity [12,24].…”

Section: Sars-cov-2 Spike Proteins Lentiviral Pseudotypesmentioning

confidence: 99%

“…The highly transmissible variant further mutated to generate sublineages BA.1, BA.2, BA.3, BA.4, and BA.5, with BA.1 and BA.2 responsible for most transmissions worldwide. Although BA.1 and BA.2 are less pathogenic [2][3][4][5][6], BA.1 evades antibody neutralization by the sera of vaccinated donors and escapes neutralization by most of the emergency use authorized therapeutic monoclonal antibodies [7][8][9][10][11][12][13][14][15][16]. BA.2 is 1.5-fold more transmissible than BA.1 and is currently the prevalent variant in the United States (85.9% as of 9 April 2022) [17].…”

Section: Introductionmentioning

confidence: 99%

“…Of the monoclonal antibodies authorized by the Food and Drug Administration for emergency use [21], Regeneron REGN10933 (Casirivimab) and REGN10987 (Imdevimab), Eli Lilly LY-CoV555 (Bamlanivimab) and LY-CoV016 (Etesevimab), and the GlaxoSmithKline/Vir monoclonal antibody Vir-7831 (Sotrovimab) have been found to be largely inactive against BA.1 and discontinued for clinical use while Evusheld, a cocktail consisting of monoclonal antibodies AZD8895 (Tixagevimab) and AZD1061 (Cilgavimab) formulated for slow release for prophylactic use in immunocompromised individuals [22] retains considerable neutralizing titer against BA.1 [12,22,23]. LY-CoV1404 (Bebtelovimab), identified in a high throughput screen of B-cells from a convalescent individual [23], was given Emergency Use Authorization in February 2022 and is currently used clinically.…”

Section: Introductionmentioning

confidence: 99%

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Resistance of SARS-CoV-2 Omicron BA.1 and BA.2 Variants to Vaccine-Elicited Sera and Therapeutic Monoclonal Antibodies

Zhou

Dcosta

Landau

et al. 2022

Viruses

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The recent emergence of the Omicron BA.1 and BA.2 variants with heavily mutated spike proteins has posed a challenge to the effectiveness of current vaccines and to monoclonal antibody therapy for severe COVID-19. After two immunizations of individuals with no history of previous SARS-CoV-2 infection with BNT162b2 vaccine, neutralizing titer against BA.1 and BA.2 were 20-fold decreased compared to titers against the parental D614G virus. A third immunization boosted overall neutralizing titers by about 5-fold but titers against BA.1 and BA.2 remained about 10-fold below that of D614G. Both Omicron variants were highly resistant to several of the emergency use authorized therapeutic monoclonal antibodies. The variants were highly resistant to Regeneron REGN10933 and REGN10987 and Lilly LY-CoV555 and LY-CoV016 while Vir-7831 and the mixture of AstraZeneca monoclonal antibodies AZD8895 and AZD1061 were significantly decreased in neutralizing titer. Strikingly, a single monoclonal antibody LY-CoV1404 potently neutralized both Omicron variants.

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“…At the time of manuscript preparation, the Omicron variant had become the dominant strain due to the highest transmissibility and the possibility to evade humoral immune response induced by all the major vaccines (14). Most of FDA approved therapeutic monoclonal antibodies including REGN10933, REG10987, LY-CoV555, LY-CoV016, AZD8895, and AZD1061 were found to be ineffective against the Omicron BA.1/BA.2 variants, while AZD7442 (Tixagevimab–Cilgavimab) and Sotrovimab were partially effective (15), (16), (17). Moreover, it was suggested that Sotrovimab (and others that form the few monoclonal antibodies, that are potentially effective against Omicron) could drive SARS-CoV-2 escape in immunocompromised patients (18).…”

Section: Discussionmentioning

confidence: 99%

Development of an Escape-resistant SARS CoV-2 Neutralizing Synthetic Nanobody

Dormeshkin

Shapira

Dubovik

et al. 2022

Preprint

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An emerging COVID-19 pandemic resulted in a global crisis, but also accelerated vaccine development and antibody discovery. In this work, we identified a number of nanomolar-range affinity VHH binders to SARS-CoV-2 variants of concern (VoC) receptor binding domains (RBD), by screening synthetic humanized antibody library with more than 1e11 diversity. In order to explore the most robust and fast method for affinity improvement, we performed affinity maturation by CDR1 and CDR2 shuffling and avidity engineering by multivalent trimeric VHH fusion protein construction. As a result, H7-Fc and G12x3-Fc binders were developed with the affinities in nM and pM range respectively. Importantly, their affinities are weakly influenced by SARS-CoV-2 VoC mutations. The plaque reduction neutralization test (PRNT) resulted in IC50 = 100 ng\ml and 9.6 ng\ml for H7-Fc and G12x3-Fc antibodies respectively for emerging Omicron variant. Therefore, these VHH could expand the present landscape of SARS-CoV-2 neutralization binders with the therapeutic potential for present and future SARS-CoV-2 variants.

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Increased resistance of SARS-CoV-2 Omicron variant to neutralization by vaccine-elicited and therapeutic antibodies

Cited by 128 publications

References 43 publications

Citizen Stance towards Mandatory COVID-19 Vaccination and Vaccine Booster Doses: A Study in Colombia, El Salvador and Spain

Citizen Stance towards Mandatory COVID-19 Vaccination and Vaccine Booster Doses: A Study in Colombia, El Salvador and Spain

Resistance of SARS-CoV-2 Omicron BA.1 and BA.2 Variants to Vaccine-Elicited Sera and Therapeutic Monoclonal Antibodies

Development of an Escape-resistant SARS CoV-2 Neutralizing Synthetic Nanobody

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