SARS-CoV-2 Spike Variants Exhibit Differential Infectivity and Neutralization Resistance to Convalescent or Post-vaccination Sera

Overview

Journal Cell Host Microbe

Publisher Cell Press

Specialties Infectious Diseases
Microbiology

Date 2021 Mar 31

PMID 33789085

Citations 132

Authors

Alona Kuzmina

Yara Khalaila

Olga Voloshin

Ayelet Keren-Naus

Liora Boehm-Cohen

Yael Raviv

Yonat Shemer-Avni

Elli Rosenberg

Ran Taube

Affiliations

Soon will be listed here.

Abstract

Toward eradicating the COVID-19 pandemic, vaccines that induce high humoral and cellular immune responses are essential. However, SARS-CoV-2 variants have begun to emerge and raise concerns, as they may potentially compromise vaccine efficiency. Here, we monitored neutralization potency of convalescent or Pfizer-BTN162b2 post-vaccination sera against pseudoviruses displaying spike proteins derived from wild-type SARS-CoV-2, or its UK-B.1.1.7 and SA-B.1.351 variants. Compared to convalescent sera, vaccination induces high titers of neutralizing antibodies, which exhibit efficient neutralization potential against pseudovirus carrying wild-type SARS-CoV-2. However, while wild-type and UK-N501Y pseudoviruses were similarly neutralized, those displaying SA-N501Y/K417N/E484K spike mutations moderately resist neutralization. Contribution of single or combined spike mutations to neutralization and infectivity were monitored, highlighting mechanisms by which viral infectivity and neutralization resistance are enhanced by N501Y or E484K/K417N mutations. Our study validates the importance of the Pfizer vaccine but raises concerns regarding its efficacy against specific SARS-CoV-2 circulating variants.

Citing Articles

Navigating the COVID-19 Therapeutic Landscape: Unveiling Novel Perspectives on FDA-Approved Medications, Vaccination Targets, and Emerging Novel Strategies.

Barghash R, Gemmati D, Awad A, Elbakry M, Tisato V, Awad K Molecules. 2024; 29(23.

PMID: 39683724 PMC: 11643501. DOI: 10.3390/molecules29235564.

Evaluating the Quality of Studies Assessing COVID-19 Vaccine Neutralizing Antibody Immunogenicity.

Katzmarzyk M, Naughton R, Sitaras I, Jacobsen H, Higdon M, Knoll M Vaccines (Basel). 2024; 12(11).

PMID: 39591141 PMC: 11598362. DOI: 10.3390/vaccines12111238.

Strengths and limitations of SARS-CoV-2 virus-like particle systems.

Sultana R, Stahelin R Virology. 2024; 601:110285.

PMID: 39536645 PMC: 11624109. DOI: 10.1016/j.virol.2024.110285.

Development of pseudotyped VSV-SARS-CoV-2 spike variants for the assessment of neutralizing antibodies.

Cimen A, Celebi Torabfam G, Tok Y, Yucebag E, Arslan N, Saribal D Bioanalysis. 2024; 16(21-22):1167-1177.

PMID: 39411978 PMC: 11583609. DOI: 10.1080/17576180.2024.2411920.

An enhanced broad-spectrum peptide inhibits Omicron variants in vivo.

Bi W, Tang K, Chen G, Xie Y, Polizzi N, DeGrado W Cell Rep Med. 2024; 5(2):101418.

PMID: 38340726 PMC: 10897629. DOI: 10.1016/j.xcrm.2024.101418.

References

Chan C, Seah S, Chye D, Massey S, Torres M, Lim A . The Fc-mediated effector functions of a potent SARS-CoV-2 neutralizing antibody, SC31, isolated from an early convalescent COVID-19 patient, are essential for the optimal therapeutic efficacy of the antibody. PLoS One. 2021; 16(6):e0253487. PMC: 8221499. DOI: 10.1371/journal.pone.0253487. View

Zang R, Gomez Castro M, McCune B, Zeng Q, Rothlauf P, Sonnek N . TMPRSS2 and TMPRSS4 promote SARS-CoV-2 infection of human small intestinal enterocytes. Sci Immunol. 2020; 5(47). PMC: 7285829. DOI: 10.1126/sciimmunol.abc3582. View

Korber B, Fischer W, Gnanakaran S, Yoon H, Theiler J, Abfalterer W . Tracking Changes in SARS-CoV-2 Spike: Evidence that D614G Increases Infectivity of the COVID-19 Virus. Cell. 2020; 182(4):812-827.e19. PMC: 7332439. DOI: 10.1016/j.cell.2020.06.043. View

Xie X, Liu Y, Liu J, Zhang X, Zou J, Fontes-Garfias C . Neutralization of SARS-CoV-2 spike 69/70 deletion, E484K and N501Y variants by BNT162b2 vaccine-elicited sera. Nat Med. 2021; 27(4):620-621. DOI: 10.1038/s41591-021-01270-4. View

Ju B, Zhang Q, Ge J, Wang R, Sun J, Ge X . Human neutralizing antibodies elicited by SARS-CoV-2 infection. Nature. 2020; 584(7819):115-119. DOI: 10.1038/s41586-020-2380-z. View

Anderson E, Rouphael N, Widge A, Jackson L, Roberts P, Makhene M . Safety and Immunogenicity of SARS-CoV-2 mRNA-1273 Vaccine in Older Adults. N Engl J Med. 2020; 383(25):2427-2438. PMC: 7556339. DOI: 10.1056/NEJMoa2028436. View

Krammer F . SARS-CoV-2 vaccines in development. Nature. 2020; 586(7830):516-527. DOI: 10.1038/s41586-020-2798-3. View

Plotkin S . Correlates of protection induced by vaccination. Clin Vaccine Immunol. 2010; 17(7):1055-65. PMC: 2897268. DOI: 10.1128/CVI.00131-10. View

Tegally H, Wilkinson E, Lessells R, Giandhari J, Pillay S, Msomi N . Sixteen novel lineages of SARS-CoV-2 in South Africa. Nat Med. 2021; 27(3):440-446. DOI: 10.1038/s41591-021-01255-3. View

10.

Brouwer P, Caniels T, van der Straten K, Snitselaar J, Aldon Y, Bangaru S . Potent neutralizing antibodies from COVID-19 patients define multiple targets of vulnerability. Science. 2020; 369(6504):643-650. PMC: 7299281. DOI: 10.1126/science.abc5902. View

11.

Hoffmann M, Kleine-Weber H, Schroeder S, Kruger N, Herrler T, Erichsen S . SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell. 2020; 181(2):271-280.e8. PMC: 7102627. DOI: 10.1016/j.cell.2020.02.052. View

12.

Zhou P, Yang X, Wang X, Hu B, Zhang L, Zhang W . A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020; 579(7798):270-273. PMC: 7095418. DOI: 10.1038/s41586-020-2012-7. View

13.

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

14.

Alsoussi W, Turner J, Case J, Zhao H, Schmitz A, Zhou J . A Potently Neutralizing Antibody Protects Mice against SARS-CoV-2 Infection. J Immunol. 2020; 205(4):915-922. PMC: 7566074. DOI: 10.4049/jimmunol.2000583. View

15.

Weisblum Y, Schmidt F, Zhang F, DaSilva J, Poston D, Lorenzi J . Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants. Elife. 2020; 9. PMC: 7723407. DOI: 10.7554/eLife.61312. View

16.

Plante J, Liu Y, Liu J, Xia H, Johnson B, Lokugamage K . Spike mutation D614G alters SARS-CoV-2 fitness. Nature. 2020; 592(7852):116-121. PMC: 8158177. DOI: 10.1038/s41586-020-2895-3. View

17.

Hoffmann M, Kleine-Weber H, Pohlmann S . A Multibasic Cleavage Site in the Spike Protein of SARS-CoV-2 Is Essential for Infection of Human Lung Cells. Mol Cell. 2020; 78(4):779-784.e5. PMC: 7194065. DOI: 10.1016/j.molcel.2020.04.022. View

18.

Zhu N, Zhang D, Wang W, Li X, Yang B, Song J . A Novel Coronavirus from Patients with Pneumonia in China, 2019. N Engl J Med. 2020; 382(8):727-733. PMC: 7092803. DOI: 10.1056/NEJMoa2001017. View

19.

Wibmer C, Ayres F, Hermanus T, Madzivhandila M, Kgagudi P, Oosthuysen B . SARS-CoV-2 501Y.V2 escapes neutralization by South African COVID-19 donor plasma. Nat Med. 2021; 27(4):622-625. DOI: 10.1038/s41591-021-01285-x. View

20.

Wang C, Li W, Drabek D, Okba N, van Haperen R, Osterhaus A . A human monoclonal antibody blocking SARS-CoV-2 infection. Nat Commun. 2020; 11(1):2251. PMC: 7198537. DOI: 10.1038/s41467-020-16256-y. View