4.8 Article

Reduced sensitivity of SARS-CoV-2 variant Delta to antibody neutralization

Journal

NATURE
Volume 596, Issue 7871, Pages 276-+

Publisher

NATURE PORTFOLIO
DOI: 10.1038/s41586-021-03777-9

Keywords

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Funding

  1. Institut Pasteur
  2. Region Ile de France (DIM1Health)
  3. Urgence COVID-19 Fundraising Campaign of Institut Pasteur
  4. Fondation pour la Recherche Medicale (FRM)
  5. ANRS
  6. Vaccine Research Institute [ANR-10-LABX-77]
  7. Labex IBEID [ANR-10-LABX-62-IBEID]
  8. ANR/FRM Flash Covid PROTEO-SARS-CoV-2
  9. IDISCOVR
  10. UPBI [ANR10-INSB-04-01]
  11. Region Ile-de-France program DIM1-Health
  12. Vaccine Research Institute
  13. Institut Pasteur, the Milieu Interieur Program [ANR-10-LABX-69-01]
  14. INSERM
  15. REACTing
  16. EU (RECOVER)
  17. Fondation de France [00106077]
  18. Strasbourg University Hospitals [PRI 7782]
  19. Programme Hospitalier de Recherche Clinique [6997]
  20. Agence Nationale de la Recherche [ANR-18-CE17-0028]
  21. Laboratoire d'Excellence TRANSPLANTEX [ANR-11-LABX-0070_TRANSPLANTEX]
  22. Institut National de la Sante et de la Recherche Medicale [UMR_S 1109]
  23. French Government's Investissement d'Avenir programme
  24. Laboratoire d'Excellence 'Integrative Biology of Emerging Infectious Diseases' [ANR-10-LABX62-IBEID]

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The SARS-CoV-2 B.1.617 Delta variant, first identified in India in 2020, has become dominant in some regions and is spreading to many countries. This variant shows resistance to certain monoclonal antibodies and antibodies in convalescent sera, as well as reduced neutralization by some COVID-19 vaccines. Administration of two doses of the vaccine is needed for a neutralizing response against the Delta variant.
The SARS-CoV-2 B.1.617 lineage was identified in October 2020 in India(1-5). Since then, it has become dominant in some regions of India and in the UK, and has spread to many other countries(6). The lineage includes three main subtypes (B1.617.1, B.1.617.2 and B.1.617.3), which contain diverse mutations in the N-terminal domain (NTD) and the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein that may increase the immune evasion potential of these variants. B.1.617.2-also termed the Delta variant-is believed to spread faster than other variants. Here we isolated an infectious strain of the Delta variant from an individual with COVID-19 who had returned to France from India. We examined the sensitivity of this strain to monoclonal antibodies and to antibodies present in sera from individuals who had recovered from COVID-19 (hereafter referred to as convalescent individuals) or who had received a COVID-19 vaccine, and then compared this strain with other strains of SARS-CoV-2. The Delta variant was resistant to neutralization by some anti-NTD and anti-RBD monoclonal antibodies, including bamlanivimab, and these antibodies showed impaired binding to the spike protein. Sera collected from convalescent individuals up to 12 months after the onset of symptoms were fourfold less potent against the Delta variant relative to the Alpha variant (B.1.1.7). Sera from individuals who had received one dose of the Pfizer or the AstraZeneca vaccine had a barely discernible inhibitory effect on the Delta variant. Administration of two doses of the vaccine generated a neutralizing response in 95% of individuals, with titres three- to fivefold lower against the Delta variant than against the Alpha variant. Thus, the spread of the Delta variant is associated with an escape from antibodies that target non-RBD and RBD epitopes of the spike protein.

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