SARS-CoV-2-variants-Monoclonal-Antibodies
SARS-CoV-2 variants

The evolution of SARS-CoV-2 variants

Like other viruses, SARS-CoV-2 evolves through mutation of its genetic code.1 These mutations create variant strains of SARS-CoV-2 that have been discovered circulating in different world populations.1
It is important to track and monitor the spread of emergent variants as they could have important implications for the diagnosis, prevention, and treatment of COVID-19.1

The purpose of this information is to share the in vitro data against tested emergent variants of concern for sotrovimab in a timely manner

In vitro pseudovirus neutralization for sotrovimab against emergent SARS-CoV-2 variants2,3

As SARS-CoV-2 evolves, it is important to evaluate if existing vaccines and treatments work against variant strains of the virus.1,4 To assess the neutralizing ability of mAbs against SARS-CoV-2 variants, pseudotyped virus assays have been developed as rapid, accurate, and convenient in vitro laboratory assessments.5,6

Scientific analysis in pseudotyped virus systems demonstrates that sotrovimab retains activity in vitro against tested emergent variants of concern.3,7,8

Methodology used: a pseudo-type virus artificially created to contain envelope proteins from the virus to be assessed, in this case Vesicular Stomatitis Virus [VSV]-luciferase pseudotyped with SARS-CoV-2 spike, is being used for the assessment of neutralization capacity against spike variants (eg, natural variants, potential escape mutations).3

WHO Label9 SARS-CoV-2
Variant Name2,3,9, *
Changes in Tested Spike Sequence2,3,* Average Fold Change
in IC50 vs Wild-type2,3"
Neutralization,
Retained/Lost2,3,†
Alpha UK (B.1.1.7) H69-, V70-, Y144-, N501Y, A570D, D614G, P681H, T716I, S982A, D1118H 2.3 Retained activity
Beta South Africa (B.1.351) L18F, D80A, D215G, R246I, K417N, E484K, N501Y, D614G, A701V 0.6 Retained activity
Gamma Brazil (P.1) D138Y, D614G, E484K, H655Y, K417T, L18F, N501Y, P26S, R190S, T1027I, T20N, V1176F 0.4 Retained activity
Delta India (B.1.617.2) T19R, G142D, E156G, F157-, R158-, L452R, T478K, D614G, P681R, D950N 1.0 Retained activity
Kappa India (B.1.617.1) T95I, G142D, E154K, L452R, E484Q, D614G, P681R, Q1071H 0.7 Retained activity
Epsilon US (B.1.427/B.1.429) S13I, W152C, L452R, D614G 0.7 Retained activity
Eta Nigeria (B.1.525) Q52R, A67V, H69-, V70-, Y144-, E484K, D614G, Q677H, F888L 0.9 Retained activity
Iota New York (B.1.526) L5F, T95I, D253G, E484K, D614G, A701V 0.6 Retained activity
Lambda Peru (C.37) G75V, T76I, del246-252, L452Q, F490S, T859N 1.5 Retained activity
Delta Plus India (AY.1) T19R, T95I, G142D, E156G, F157-, R158-, W258L, K417N, L452R, T478K, D614G, P681R, D950N 1.1 Retained activity
Delta Plus India (AY.2) T19R, V70F, G142D, E156G, F157-, R158-, A222V, K417N, L452R, T478K, D614G, P681R, D950N 1.3 Retained activity
N/A Mexico/Swiss (B.1.1.519) T478K, D614G, P681H, T732A 0.8 Retained activity
N/A Scotland (B.1.258) H69-, V70-, N439K, D614G 0.9 Retained activity
N/A US (R.2) E484K, D614G, Q677H, T732S, E1202Q 0.8 Retained activity
N/A Liverpool (A.23.1) R102I, F157L, V367F, E484K, Q613H, P681R 1.1 Retained activity
N/A Bristol (B.1.1.7 + E484K) H69-, V70-, Y144-, E484K, N501Y, A570D, D614G, P681H, T716I, S982A, D1118H 1.7 Retained activity
N/A Cameroon (B.1.619) I210T, N440K, E484K, D614G, D936N, S939F, T1027I 1.3 Retained activity

Table last updated June 24, 20213

*A SARS-CoV-2 variant has one or more mutations that differentiate it from other variant strains of the virus.1 In an effort to understand the outbreak and global trends, scientists compare the genetic differences to identify variants and how they relate to one another.1

Retained activity is defined as <3-fold reduction in average fold change3; the clinical significance of pseudovirus neutralization data is unknown.

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References

  1. Centers for Disease Control and Prevention, SARS-CoV Variant Classifications and Definitions. Available at https://www.cdc.gov/coronavirus/2019-ncov/variants/variant-info.html. Accessed June 29, 2021.
  2. US Food and Drug Administration, Sotrovimab Fact Sheet for Healthcare Providers. Available at https://www.fda.gov/media/149534/download. Accessed June 18, 2021
  3. Cathcart AL, Havenar-Daughton C, Lempp FL, et al. The dual function monoclonal antibodies VIR-7831 and VIR-7832 demonstrate potent in vitro and in vivo activity against SARS-CoV-2. bioRxiv. 2021. doi:10.1101/2021.03.09.434607.
  4. GISAID database. Available at https://www.gisaid.org/phylodynamics/global/nextstrain/. Accessed June 18, 2021.
  5. Schmidt F, Weisblum Y, Muecksch, F, et al. Measuring SARS-CoV-2 neutralizing antibody activity using pseudotyped and chimeric viruses. Journal of Experimental Medicine. 2020;217(11):e20201181.
  6. Neerukonda SN, Vassell R, Herrup R, et al. Establishment of a well-characterized SARS-CoV-2 lentiviral pseudovirus neutralization assay using 293T cells with stable expression of ACE2 and TMPRSS2. PLoS One. 2021;16(3):e0248348.
  7. Thompson EC, Rosen LE, Shepherd JG, et al. Circulating SARS-CoV-2 spike N439K variants maintain fitness while evading antibody-mediated immunity. Cell. 2021;184(5):1171-1187.e20.
  8. Wang P, Nair MS, Liu L, et al. Antibody Resistance of SARS-CoV-2 Variants B.1.351 and B.1.1.7. Nature. 2021;593(7857):130-135.
  9. World Health Organization, Tracking SARS-CoV-2 Variants. Available at https://www.who.int/en/activities/tracking-SARS-CoV-2-variants/. Accessed June 29, 2021.

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