Decreased neutralization of SARS-CoV-2 global variants by therapeutic anti-spike protein monoclonal antibodies

Tada, Takuya; Dcosta, Belinda M; Zhou, Hao; Vaill, Ada; Kazmierski, Wes; Landau, Nathaniel R.

doi:10.1101/2021.02.18.431897

Cited by 69 publications

(66 citation statements)

References 32 publications

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“…In contrast, mRNA-1273 (21,22) and BNT162b2 (21,24) vaccine-induced sera showed ~3-8-fold reductions in crossneutralization of B.1.351. The REGN-COV2 antibody cocktail showed a ~10-fold reduction in cross-on May 10, 2021 by guest http://jvi.asm.org/ Downloaded from neutralization of B.1.351 in one unpublished report (25). In another unpublished report, REGN-COV2 retained cross-neutralization of B.1.351 while LY-CoV555 showed a >100-fold reduction in IC50 (21).…”

Section: Introductionmentioning

confidence: 93%

Correlates of Neutralization against SARS-CoV-2 Variants of Concern by Early Pandemic Sera

Vidal

Collier

et al. 2021

J Virol

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Emerging SARS-CoV-2 variants of concern that overcome natural and vaccine-induced immunity threaten to exacerbate the COVID-19 pandemic. Increasing evidence suggests that neutralizing antibody (NAb) responses are a primary mechanism of protection against infection. However, little is known about the extent and mechanisms by which natural immunity acquired during the early COVID-19 pandemic confers cross-neutralization of emerging variants. In this study, we investigated cross-neutralization of the B.1.1.7 and B.1.351 SARS-CoV-2 variants in a well-characterized cohort of early pandemic convalescent subjects. We observed modestly decreased cross-neutralization of B.1.1.7 but a substantial 4.8-fold reduction in cross-neutralization of B.1.351. Correlates of cross-neutralization included receptor binding domain (RBD) and N-terminal domain (NTD) binding antibodies, homologous NAb titers, and Membrane-directed T cell responses. These data shed light on cross-neutralization of emerging variants by early pandemic convalescent immune responses. IMPORTANCE Widespread immunity to SARS-CoV-2 will be necessary to end the COVID-19 pandemic. Neutralizing antibody (NAb) responses are a critical component of immunity that can be stimulated by natural infection as well as vaccines. However, SARS-CoV-2 variants are emerging that contain mutations in the Spike gene that promote evasion from NAb responses. These variants may therefore delay control of the COVID-19 pandemic. We studied whether NAb responses from early COVID-19 convalescent patients are effective against the two SARS-CoV-2 variants B.1.1.7 and B.1.351. We observed that the B.1.351 variant demonstrates significantly reduced susceptibility to early pandemic NAb responses. We additionally characterized virologic, immunologic, and clinical features that correlate with cross-neutralization. These studies increase our understanding of emerging SARS-CoV-2 variants.

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Section: Introductionmentioning

confidence: 93%

Correlates of Neutralization against SARS-CoV-2 Variants of Concern by Early Pandemic Sera

Vidal

Collier

et al. 2021

J Virol

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“…Donor age and gender were not reported. Regeneron monoclonal antibodies (REGN10933 and REGN10987) were prepared as previously described [36].…”

Section: Human Sera and Monoclonal Antibodiesmentioning

confidence: 99%

B.1.526 SARS-CoV-2 variants identified in New York City are neutralized by vaccine-elicited and therapeutic monoclonal antibodies

Zhou

Dcosta

Samanovic

et al. 2021

Preprint

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DNA sequence analysis recently identified the novel SARS-CoV-2 variant B.1.526 that is spreading at an alarming rate in the New York City area. Two versions of the variant were identified, both with the prevalent D614G mutation in the spike protein together with four novel point mutations and with an E484K or S477N mutation in the receptor binding domain, raising concerns of possible resistance to vaccine-elicited and therapeutic antibodies. We report that convalescent sera and vaccine-elicited antibodies retain full neutralizing titer against the S477N B.1.526 variant and neutralize the E484K version with a modest 3.5-fold decrease in titer as compared to D614G. The E484K version was neutralized with a 12-fold decrease in titer by the REGN10933 monoclonal antibody but the combination cocktail with REGN10987 was fully active. The findings suggest that current vaccines and therapeutic monoclonal antibodies will remain protective against the B.1.526 variants. The findings further support the value of wide-spread vaccination.

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“…11,14,15 In contrast, many of the other monoclonal antibodies being developed for Covid-19 bind to the receptor-binding motif that engages the angiotensin-converting enzyme 2 (ACE2) receptor and is one of the most mutable and immunogenic regions of the virus; in some cases, these antibodies do not retain activity against the variants. [16][17][18][19] Sotrovimab contains a two-amino acid Fc modification (termed LS) to increase half-life and potentially improve bioavailability in the respiratory mucosa through enhanced engagement with the neonatal Fc receptor. [20][21][22] This modification potentially allows therapeutic concentrations for longer durations.…”

Section: Introductionmentioning

confidence: 99%

Early Covid-19 Treatment With SARS-CoV-2 Neutralizing Antibody Sotrovimab

Gupta

Gonzalez‐Rojas²,

Juárez³

et al. 2021

Preprint

215

300

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Background: Coronavirus disease 2019 (Covid-19) disproportionately results in hospitalization and death in older patients and those with underlying comorbidities. Sotrovimab is a pan-sarbecovirus monoclonal antibody designed to treat such high-risk patients early in the course of disease, thereby preventing Covid-19 progression. Methods: In this ongoing, multicenter, double-blind, phase 3 trial, nonhospitalized patients with symptomatic Covid-19 and at least one risk factor for disease progression were randomized (1:1) to an intravenous infusion of sotrovimab 500 mg or placebo. The primary efficacy endpoint was the proportion of patients with Covid-19 progression, defined as hospitalization longer than 24 hours or death, through day 29. Results: In this preplanned interim analysis, which included an intent-to-treat population of 583 patients (sotrovimab, 291; placebo, 292), the primary efficacy endpoint was met. The risk of Covid-19 progression was significantly reduced by 85% (97.24% confidence interval, 44% to 96%; P = 0.002) with a total of three (1%) patients progressing to the primary endpoint in the sotrovimab group versus 21 (7%) patients in the placebo group. All five patients admitted to intensive care, including one who died by day 29, received placebo. Safety was assessed in 868 patients (sotrovimab, 430; placebo, 438). Adverse events were reported by 17% and 19% of patients receiving sotrovimab and placebo, respectively; serious adverse events were less common with sotrovimab (2%) versus placebo (6%). Conclusion: Sotrovimab reduced progression of Covid-19 in patients with mild/moderate disease, was well tolerated, and no safety signals were identified. Funded by Vir Biotechnology, Inc. and GlaxoSmithKline; ClinicalTrials.gov NCT04545060

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Decreased neutralization of SARS-CoV-2 global variants by therapeutic anti-spike protein monoclonal antibodies

Cited by 69 publications

References 32 publications

Correlates of Neutralization against SARS-CoV-2 Variants of Concern by Early Pandemic Sera

Correlates of Neutralization against SARS-CoV-2 Variants of Concern by Early Pandemic Sera

B.1.526 SARS-CoV-2 variants identified in New York City are neutralized by vaccine-elicited and therapeutic monoclonal antibodies

Early Covid-19 Treatment With SARS-CoV-2 Neutralizing Antibody Sotrovimab

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