Extremely potent monoclonal antibodies neutralize Omicron and other SARS-CoV-2 variants

Abstract

The ongoing coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has triggered a devastating global health, social and economic crisis. The RNA nature and broad circulation of this virus facilitate the accumulation of mutations, leading to the continuous emergence of variants of concern with increased transmissibility or pathogenicity1. This poses a major challenge to the effectiveness of current vaccines and therapeutic antibodies1,2. Thus, there is an urgent need for effective therapeutic and preventive measures with a broad spectrum of action, especially against variants with an unparalleled number of mutations such as the recently emerged Omicron variant, which is rapidly spreading across the globe3. Here, we used combinatorial antibody phage-display libraries from convalescent COVID-19 patients to generate monoclonal antibodies against the receptor-binding domain of the SARS-CoV-2 spike protein with ultrapotent neutralizing activity. One such antibody, NE12, neutralizes an early isolate, the WA-1 strain, as well as the Alpha and Delta variants with half-maximal inhibitory concentrations at picomolar level. A second antibody, NA8, has an unusual breadth of neutralization, with picomolar activity against both the Beta and Omicron variants. The prophylactic and therapeutic efficacy of NE12 and NA8 was confirmed in preclinical studies in the golden Syrian hamster model. Analysis by cryo-EM illustrated the structural basis for the neutralization properties of NE12 and NA8. Potent and broadly neutralizing antibodies against conserved regions of the SARS-CoV-2 spike protein may play a key role against future variants of concern that evade immune control.

Emergence of SARS-CoV-2 Omicron (B.1.1.529) variant, salient features, high global health concerns and strategies to counter it amid ongoing COVID-19 pandemic

“…Early modelling studies have predicted that the REGN-COV2 (Casirivimab and Imdevimab), as well as the Rockefeller University antibody C135 are still efficacious against the omicron ( Chen et al, 2021a ; Aleem et al, 2022 ). NA8 and NE12 are the prophylactic and therapeutic antibodies that are developed using combinatorial antibody phage-display library methodology, and are effective against Omicron in picomolar concentrations ( Chen et al, 2022 ). Future strategy to combat Omicron requires high potency drugs which could reduce viral replication and spreading, and be effective against all the circulating variants, including any possible variants that could emerge (Fang “Flora” Fang and Shi, 2021 ; Mohiuddin and Kasahara, 2021 ).…”

Susceptibility of SARS-CoV-2 Omicron Variants to Therapeutic Monoclonal Antibodies: Systematic Review and Meta-Analysis

“…As of February 22, 2022, 31 studies met the search criteria (Figure 1). Twelve of the studies were reported in a peer-reviewed publication [10][11][12][13][14][15][16][17][18][19][20][21]; 19 were published as preprints [22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40]. Two additional studies comprised data available on the NIH National Center for Advancing Translational Sciences (NCATS) SARS-CoV-2 Variants and Therapeutics open data portal [41,42].…”

New SARS-CoV-2 Omicron variant — clinical picture, treatment, prevention (literature review)

“…певтическую активность в отношении SARS-CoV-2, включая B.1.351 и B.1.1.529, в то время как клинические исследования не представили убедительных данных в отношении штамма Омикрон [47].…”