Vaccines (May 2024)

Antigenic Characterization of Circulating and Emerging SARS-CoV-2 Variants in the U.S. throughout the Delta to Omicron Waves

  • Han Di,
  • Elizabeth A. Pusch,
  • Joyce Jones,
  • Nicholas A. Kovacs,
  • Norman Hassell,
  • Mili Sheth,
  • Kelly Sabrina Lynn,
  • Matthew W. Keller,
  • Malania M. Wilson,
  • Lisa M. Keong,
  • Dan Cui,
  • So Hee Park,
  • Reina Chau,
  • Kristine A. Lacek,
  • Jimma D. Liddell,
  • Marie K. Kirby,
  • Genyan Yang,
  • Monique Johnson,
  • Sharmi Thor,
  • Natosha Zanders,
  • Chenchen Feng,
  • Diya Surie,
  • Jennifer DeCuir,
  • Sandra N. Lester,
  • Lydia Atherton,
  • Heather Hicks,
  • Azaibi Tamin,
  • Jennifer L. Harcourt,
  • Melissa M. Coughlin,
  • Wesley H. Self,
  • Jillian P. Rhoads,
  • Kevin W. Gibbs,
  • David N. Hager,
  • Nathan I. Shapiro,
  • Matthew C. Exline,
  • Adam S. Lauring,
  • Benjamin Rambo-Martin,
  • Clinton R. Paden,
  • Rebecca J. Kondor,
  • Justin S. Lee,
  • John R. Barnes,
  • Natalie J. Thornburg,
  • Bin Zhou,
  • David E. Wentworth,
  • Charles Todd Davis

DOI
https://doi.org/10.3390/vaccines12050505
Journal volume & issue
Vol. 12, no. 5
p. 505

Abstract

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved into numerous lineages with unique spike mutations and caused multiple epidemics domestically and globally. Although COVID-19 vaccines are available, new variants with the capacity for immune evasion continue to emerge. To understand and characterize the evolution of circulating SARS-CoV-2 variants in the U.S., the Centers for Disease Control and Prevention (CDC) initiated the National SARS-CoV-2 Strain Surveillance (NS3) program and has received thousands of SARS-CoV-2 clinical specimens from across the nation as part of a genotype to phenotype characterization process. Focus reduction neutralization with various antisera was used to antigenically characterize 143 SARS-CoV-2 Delta, Mu and Omicron subvariants from selected clinical specimens received between May 2021 and February 2023, representing a total of 59 unique spike protein sequences. BA.4/5 subvariants BU.1, BQ.1.1, CR.1.1, CQ.2 and BA.4/5 + D420N + K444T; BA.2.75 subvariants BM.4.1.1, BA.2.75.2, CV.1; and recombinant Omicron variants XBF, XBB.1, XBB.1.5 showed the greatest escape from neutralizing antibodies when analyzed against post third-dose original monovalent vaccinee sera. Post fourth-dose bivalent vaccinee sera provided better protection against those subvariants, but substantial reductions in neutralization titers were still observed, especially among BA.4/5 subvariants with both an N-terminal domain (NTD) deletion and receptor binding domain (RBD) substitutions K444M + N460K and recombinant Omicron variants. This analysis demonstrated a framework for long-term systematic genotype to antigenic characterization of circulating and emerging SARS-CoV-2 variants in the U.S., which is critical to assessing their potential impact on the effectiveness of current vaccines and antigen recommendations for future updates.

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