Antibody Escape of SARS-CoV-2 Omicron BA.4 and BA.5 from Vaccine and BA.1 Serum

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 2022 Jun 30

PMID 35772405

Authors

Aekkachai Tuekprakhon

Rungtiwa Nutalai

Aiste Dijokaite-Guraliuc

Daming Zhou

Helen M Ginn

Muneeswaran Selvaraj

Chang Liu

Alexander J Mentzer

Piyada Supasa

Helen M E Duyvesteyn

Raksha Das

Donal Skelly

Thomas G Ritter

Ali Amini

Sagida Bibi

Sandra Adele

Sile Ann Johnson

Bede Constantinides

Hermione Webster

Nigel Temperton

Paul Klenerman

Eleanor Barnes

Susanna J Dunachie

Derrick Crook

Andrew J Pollard

Teresa Lambe

Philip Goulder

Neil G Paterson

Mark A Williams

David R Hall

Elizabeth E Fry

Jiandong Huo

Juthathip Mongkolsapaya

Jingshan Ren

David I Stuart

Gavin R Screaton

Affiliations

Soon will be listed here.

Abstract

The Omicron lineage of SARS-CoV-2, which was first described in November 2021, spread rapidly to become globally dominant and has split into a number of sublineages. BA.1 dominated the initial wave but has been replaced by BA.2 in many countries. Recent sequencing from South Africa's Gauteng region uncovered two new sublineages, BA.4 and BA.5, which are taking over locally, driving a new wave. BA.4 and BA.5 contain identical spike sequences, and although closely related to BA.2, they contain further mutations in the receptor-binding domain of their spikes. Here, we study the neutralization of BA.4/5 using a range of vaccine and naturally immune serum and panels of monoclonal antibodies. BA.4/5 shows reduced neutralization by the serum from individuals vaccinated with triple doses of AstraZeneca or Pfizer vaccine compared with BA.1 and BA.2. Furthermore, using the serum from BA.1 vaccine breakthrough infections, there are, likewise, significant reductions in the neutralization of BA.4/5, raising the possibility of repeat Omicron infections.

Citing Articles

Impact of African-Specific ACE2 Polymorphisms on Omicron BA.4/5 RBD Binding and Allosteric Communication Within the ACE2-RBD Protein Complex.

Barozi V, Tastan Bishop O Int J Mol Sci. 2025; 26(3).

PMID: 39941135 PMC: 11818624. DOI: 10.3390/ijms26031367.

SARS-CoV-2 Variants: Genetic Insights, Epidemiological Tracking, and Implications for Vaccine Strategies.

Alhamlan F, Al-Qahtani A Int J Mol Sci. 2025; 26(3).

PMID: 39941026 PMC: 11818319. DOI: 10.3390/ijms26031263.

Humoral and cellular immune durability of different COVID-19 vaccine platforms following homologous/heterologous boosters: one-year post vaccination.

Awadalla M, AlRawi H, Henawi R, Barnawi F, Alkadi H, Alyami A Front Immunol. 2025; 16:1526444.

PMID: 39911379 PMC: 11794813. DOI: 10.3389/fimmu.2025.1526444.

SARS-CoV-2 surveillance in a hospital and control of an outbreak on a geriatric ward using whole genome sequencing.

Schmidt H, Lemmermann N, Linke M, Bikar S, Runkel S, Schweiger-Seemann S Infect Prev Pract. 2025; 6(3):100383.

PMID: 39886645 PMC: 11780369. DOI: 10.1016/j.infpip.2024.100383.

A human antibody derived from original SARS-CoV-2 infection effectively neutralizes omicron.

Li T, Zhou B, Dong H, Lavillette D, Li D Adv Biotechnol (Singap). 2025; 2(1):2.

PMID: 39883245 PMC: 11740836. DOI: 10.1007/s44307-024-00011-1.

References

Zahradnik J, Marciano S, Shemesh M, Zoler E, Harari D, Chiaravalli J . SARS-CoV-2 variant prediction and antiviral drug design are enabled by RBD in vitro evolution. Nat Microbiol. 2021; 6(9):1188-1198. DOI: 10.1038/s41564-021-00954-4. View

Cele S, Jackson L, Khoury D, Khan K, Moyo-Gwete T, Tegally H . Omicron extensively but incompletely escapes Pfizer BNT162b2 neutralization. Nature. 2022; 602(7898):654-656. PMC: 8866126. DOI: 10.1038/s41586-021-04387-1. View

Dejnirattisai W, Zhou D, Ginn H, Duyvesteyn H, Supasa P, Case J . The antigenic anatomy of SARS-CoV-2 receptor binding domain. Cell. 2021; 184(8):2183-2200.e22. PMC: 7891125. DOI: 10.1016/j.cell.2021.02.032. View

Cerutti G, Guo Y, Zhou T, Gorman J, Lee M, Rapp M . Potent SARS-CoV-2 neutralizing antibodies directed against spike N-terminal domain target a single supersite. Cell Host Microbe. 2021; 29(5):819-833.e7. PMC: 7953435. DOI: 10.1016/j.chom.2021.03.005. View

Huo J, Zhao Y, Ren J, Zhou D, Duyvesteyn H, Ginn H . Neutralization of SARS-CoV-2 by Destruction of the Prefusion Spike. Cell Host Microbe. 2020; 28(3):445-454.e6. PMC: 7303615. DOI: 10.1016/j.chom.2020.06.010. View

Walls A, Tortorici M, Snijder J, Xiong X, Bosch B, Rey F . Tectonic conformational changes of a coronavirus spike glycoprotein promote membrane fusion. Proc Natl Acad Sci U S A. 2017; 114(42):11157-11162. PMC: 5651768. DOI: 10.1073/pnas.1708727114. View

Liu C, Ginn H, Dejnirattisai W, Supasa P, Wang B, Tuekprakhon A . Reduced neutralization of SARS-CoV-2 B.1.617 by vaccine and convalescent serum. Cell. 2021; 184(16):4220-4236.e13. PMC: 8218332. DOI: 10.1016/j.cell.2021.06.020. View

Nie J, Li Q, Wu J, Zhao C, Hao H, Liu H . Establishment and validation of a pseudovirus neutralization assay for SARS-CoV-2. Emerg Microbes Infect. 2020; 9(1):680-686. PMC: 7144318. DOI: 10.1080/22221751.2020.1743767. View

Liu C, Zhou D, Nutalai R, Duyvesteyn H, Tuekprakhon A, Ginn H . The antibody response to SARS-CoV-2 Beta underscores the antigenic distance to other variants. Cell Host Microbe. 2021; 30(1):53-68.e12. PMC: 8626228. DOI: 10.1016/j.chom.2021.11.013. View

10.

Dong J, Zost S, Greaney A, Starr T, Dingens A, Chen E . Genetic and structural basis for SARS-CoV-2 variant neutralization by a two-antibody cocktail. Nat Microbiol. 2021; 6(10):1233-1244. PMC: 8543371. DOI: 10.1038/s41564-021-00972-2. View

11.

Winter G, Waterman D, Parkhurst J, Brewster A, Gildea R, Gerstel M . DIALS: implementation and evaluation of a new integration package. Acta Crystallogr D Struct Biol. 2018; 74(Pt 2):85-97. PMC: 5947772. DOI: 10.1107/S2059798317017235. View

12.

Lan J, Ge J, Yu J, Shan S, Zhou H, Fan S . Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor. Nature. 2020; 581(7807):215-220. DOI: 10.1038/s41586-020-2180-5. View

13.

Flaxman A, Marchevsky N, Jenkin D, Aboagye J, Aley P, Angus B . Reactogenicity and immunogenicity after a late second dose or a third dose of ChAdOx1 nCoV-19 in the UK: a substudy of two randomised controlled trials (COV001 and COV002). Lancet. 2021; 398(10304):981-990. PMC: 8409975. DOI: 10.1016/S0140-6736(21)01699-8. View

14.

Dejnirattisai W, Zhou D, Supasa P, Liu C, Mentzer A, Ginn H . Antibody evasion by the P.1 strain of SARS-CoV-2. Cell. 2021; 184(11):2939-2954.e9. PMC: 8008340. DOI: 10.1016/j.cell.2021.03.055. View

15.

Wrapp D, Wang N, Corbett K, Goldsmith J, Hsieh C, Abiona O . Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science. 2020; 367(6483):1260-1263. PMC: 7164637. DOI: 10.1126/science.abb2507. View

16.

Yuan M, Liu H, Wu N, Lee C, Zhu X, Zhao F . Structural basis of a shared antibody response to SARS-CoV-2. Science. 2020; 369(6507):1119-1123. PMC: 7402627. DOI: 10.1126/science.abd2321. View

17.

Folegatti P, Ewer K, Aley P, Angus B, Becker S, Belij-Rammerstorfer S . Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial. Lancet. 2020; 396(10249):467-478. PMC: 7445431. DOI: 10.1016/S0140-6736(20)31604-4. View

18.

Aricescu A, Lu W, Jones E . A time- and cost-efficient system for high-level protein production in mammalian cells. Acta Crystallogr D Biol Crystallogr. 2006; 62(Pt 10):1243-50. DOI: 10.1107/S0907444906029799. View

19.

Pinto D, Park Y, Beltramello M, Walls A, Tortorici M, Bianchi S . Cross-neutralization of SARS-CoV-2 by a human monoclonal SARS-CoV antibody. Nature. 2020; 583(7815):290-295. DOI: 10.1038/s41586-020-2349-y. View

20.

Domingo E . Mechanisms of viral emergence. Vet Res. 2010; 41(6):38. PMC: 2831534. DOI: 10.1051/vetres/2010010. View