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Abstract

Background

The risk of SARS-CoV-2 (re-)infection remains present given waning of vaccine-induced and infection-acquired immunity, and ongoing circulation of new variants.

Aim

To develop a method that predicts virus neutralisation and disease protection based on variant-specific antibody measurements to SARS-CoV-2 antigens.

Methods

To correlate antibody and neutralisation titres, we collected 304 serum samples from individuals with either vaccine-induced or infection-acquired SARS-CoV-2 immunity. Using the association between antibody and neutralisation titres, we developed a prediction model for SARS-CoV-2-specific neutralisation titres. From predicted neutralising titres, we inferred protection estimates to symptomatic and severe COVID-19 using previously described relationships between neutralisation titres and protection estimates. We estimated population immunity in a French longitudinal cohort of 905 individuals followed from April 2020 to November 2021.

Results

We demonstrated a strong correlation between anti-SARS-CoV-2 antibodies measured using a low cost high-throughput assay and antibody response capacity to neutralise live virus. Participants with a single vaccination or immunity caused by infection were especially vulnerable to symptomatic or severe COVID-19. While the median reduced risk of COVID-19 from Delta variant infection in participants with three vaccinations was 96% (IQR: 94–98), median reduced risk among participants with infection-acquired immunity was only 42% (IQR: 22–66).

Conclusion

Our results are consistent with data from vaccine effectiveness studies, indicating the robustness of our approach. Our multiplex serological assay can be readily adapted to study new variants and provides a framework for development of an assay that would include protection estimates.

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/content/10.2807/1560-7917.ES.2023.28.25.2200681
2023-06-22
2024-04-27
http://instance.metastore.ingenta.com/content/10.2807/1560-7917.ES.2023.28.25.2200681
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References

  1. World Health Organization (WHO). Weekly epidemiological update on COVID-19—16 March 2023. Geneva: WHO; 2023. Available from: https://www.who.int/publications/m/item/weekly-epidemiological-update-on-covid-19---16-march-2023
  2. European Centre for Disease Prevention and Control (ECDC). COVID-19 Vaccine Tracker. Stockholm: ECDC. [Accessed: 16 Mar 2023]. Available from: https://vaccinetracker.ecdc.europa.eu/public/extensions/covid-19/vaccine-tracker.html#uptake-tab
  3. Feng S, Phillips DJ, White T, Sayal H, Aley PK, Bibi S, et al. Correlates of protection against symptomatic and asymptomatic SARS-CoV-2 infection. Nat Med. 2021;27(11):2032-40.  https://doi.org/10.1038/s41591-021-01540-1  PMID: 34588689 
  4. Plotkin SA. Vaccines: correlates of vaccine-induced immunity. Clin Infect Dis. 2008;47(3):401-9.  https://doi.org/10.1086/589862  PMID: 18558875 
  5. Khoury DS, Cromer D, Reynaldi A, Schlub TE, Wheatley AK, Juno JA, et al. Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection. Nat Med. 2021;27(7):1205-11.  https://doi.org/10.1038/s41591-021-01377-8  PMID: 34002089 
  6. Earle KA, Ambrosino DM, Fiore-Gartland A, Goldblatt D, Gilbert PB, Siber GR, et al. Evidence for antibody as a protective correlate for COVID-19 vaccines. Vaccine. 2021;39(32):4423-8.  https://doi.org/10.1016/j.vaccine.2021.05.063  PMID: 34210573 
  7. Cohen JA, Stuart RM, Rosenfeld K, Lyons H, White M, Kerr CC, et al. Quantifying the role of naturally- and vaccine-derived neutralizing antibodies as a correlate of protection against COVID-19 variants. medRxiv. 2021:2021.05.31.21258018 https://doi.org/10.1101/2021.05.31.21258018 
  8. Gilbert PB, Donis RO, Koup RA, Fong Y, Plotkin SA, Follmann D. A covid-19 milestone attained - a correlate of protection for vaccines. N Engl J Med. 2022;387(24):2203-6.  https://doi.org/10.1056/NEJMp2211314  PMID: 36507702 
  9. Planas D, Bruel T, Grzelak L, Guivel-Benhassine F, Staropoli I, Porrot F, et al. Sensitivity of infectious SARS-CoV-2 B.1.1.7 and B.1.351 variants to neutralizing antibodies. Nat Med. 2021;27(5):917-24.  https://doi.org/10.1038/s41591-021-01318-5  PMID: 33772244 
  10. Planas D, Veyer D, Baidaliuk A, Staropoli I, Guivel-Benhassine F, Rajah MM, et al. Reduced sensitivity of SARS-CoV-2 variant Delta to antibody neutralization. Nature. 2021;596(7871):276-80.  https://doi.org/10.1038/s41586-021-03777-9  PMID: 34237773 
  11. Cromer D, Steain M, Reynaldi A, Schlub TE, Wheatley AK, Juno JA, et al. Neutralising antibody titres as predictors of protection against SARS-CoV-2 variants and the impact of boosting: a meta-analysis. Lancet Microbe. 2022;3(1):e52-61.  https://doi.org/10.1016/S2666-5247(21)00267-6  PMID: 34806056 
  12. Planas D, Saunders N, Maes P, Guivel-Benhassine F, Planchais C, Buchrieser J, et al. Considerable escape of SARS-CoV-2 Omicron to antibody neutralization. Nature. 2022;602(7898):671-5.  https://doi.org/10.1038/s41586-021-04389-z  PMID: 35016199 
  13. Fontanet A, Tondeur L, Grant R, Temmam S, Madec Y, Bigot T, et al. SARS-CoV-2 infection in schools in a northern French city: a retrospective serological cohort study in an area of high transmission, France, January to April 2020. Euro Surveill. 2021;26(15):2001695.  https://doi.org/10.2807/1560-7917.ES.2021.26.15.2001695  PMID: 33860747 
  14. Pelleau S, Woudenberg T, Rosado J, Donnadieu F, Garcia L, Obadia T, et al. Kinetics of the severe acute respiratory syndrome coronavirus 2 antibody response and serological estimation of time since infection. J Infect Dis. 2021;224(9):1489-99.  https://doi.org/10.1093/infdis/jiab375  PMID: 34282461 
  15. Garcia L, Woudenberg T, Rosado J, Dyer AH, Donnadieu F, Planas D, et al. Kinetics of the SARS-CoV-2 antibody avidity response following infection and vaccination. Viruses. 2022;14(7):1491.  https://doi.org/10.3390/v14071491  PMID: 35891471 
  16. Rosado J, Pelleau S, Cockram C, Merkling SH, Nekkab N, Demeret C, et al. Multiplex assays for the identification of serological signatures of SARS-CoV-2 infection: an antibody-based diagnostic and machine learning study. Lancet Microbe. 2021;2(2):e60-9.  https://doi.org/10.1016/S2666-5247(20)30197-X  PMID: 33521709 
  17. Woudenberg T, Pelleau S, Anna F, Attia M, Donnadieu F, Gravet A, et al. Humoral immunity to SARS-CoV-2 and seasonal coronaviruses in children and adults in north-eastern France. EBioMedicine. 2021;70:103495.  https://doi.org/10.1016/j.ebiom.2021.103495  PMID: 34304047 
  18. Hozé N, Paireau J, Lapidus N, Tran Kiem C, Salje H, Severi G, et al. Monitoring the proportion of the population infected by SARS-CoV-2 using age-stratified hospitalisation and serological data: a modelling study. Lancet Public Health. 2021;6(6):e408-15.  https://doi.org/10.1016/S2468-2667(21)00064-5  PMID: 33838700 
  19. Lauring AS, Tenforde MW, Chappell JD, Gaglani M, Ginde AA, McNeal T, et al. Clinical severity and mRNA vaccine effectiveness for Omicron, Delta, and Alpha SARS-CoV-2 variants in the United States: a prospective observational study. medRxiv. 2022:2022.02.06.22270558 https://doi.org/10.1101/2022.02.06.22270558 
  20. Buchan SA, Chung H, Brown KA, Austin PC, Fell DB, Gubbay JB, et al. Estimated effectiveness of COVID-19 vaccines against Omicron or Delta symptomatic infection and severe outcomes. JAMA Netw Open. 2022;5(9):e2232760.  https://doi.org/10.1001/jamanetworkopen.2022.32760  PMID: 36136332 
  21. Nasreen S, Chung H, He S, Brown KA, Gubbay JB, Buchan SA, et al. Effectiveness of COVID-19 vaccines against symptomatic SARS-CoV-2 infection and severe outcomes with variants of concern in Ontario. Nat Microbiol. 2022;7(3):379-85.  https://doi.org/10.1038/s41564-021-01053-0  PMID: 35132198 
  22. Skowronski DM, Febriani Y, Ouakki M, Setayeshgar S, El Adam S, Zou M, et al. Two-dose severe acute respiratory syndrome coronavirus 2 vaccine effectiveness with mixed schedules and extended dosing intervals: test-negative design studies from British Columbia and Quebec, Canada. Clin Infect Dis. 2022;75(11):1980-92.  https://doi.org/10.1093/cid/ciac290  PMID: 35438175 
  23. Tang P, Hasan MR, Chemaitelly H, Yassine HM, Benslimane FM, Al Khatib HA, et al. BNT162b2 and mRNA-1273 COVID-19 vaccine effectiveness against the SARS-CoV-2 Delta variant in Qatar. Nat Med. 2021;27(12):2136-43.  https://doi.org/10.1038/s41591-021-01583-4  PMID: 34728831 
  24. Andrews N, Stowe J, Kirsebom F, Toffa S, Sachdeva R, Gower C, et al. Effectiveness of COVID-19 booster vaccines against COVID-19-related symptoms, hospitalization and death in England. Nat Med. 2022;28(4):831-7.  https://doi.org/10.1038/s41591-022-01699-1  PMID: 35045566 
  25. Accorsi EK, Britton A, Fleming-Dutra KE, Smith ZR, Shang N, Derado G, et al. Association between 3 doses of mRNA COVID-19 vaccine and symptomatic infection caused by the SARS-CoV-2 Omicron and Delta variants. JAMA. 2022;327(7):639-51.  https://doi.org/10.1001/jama.2022.0470  PMID: 35060999 
  26. Nordström P, Ballin M, Nordström A. Risk of SARS-CoV-2 reinfection and COVID-19 hospitalisation in individuals with natural and hybrid immunity: a retrospective, total population cohort study in Sweden. Lancet Infect Dis. 2022;22(6):781-90.  https://doi.org/10.1016/S1473-3099(22)00143-8  PMID: 35366962 
  27. Bruel T, Pinaud L, Tondeur L, Planas D, Staropoli I, Porrot F, et al. Neutralising antibody responses to SARS-CoV-2 omicron among elderly nursing home residents following a booster dose of BNT162b2 vaccine: A community-based, prospective, longitudinal cohort study. EClinicalMedicine. 2022;51:101576.  https://doi.org/10.1016/j.eclinm.2022.101576  PMID: 35891947 
  28. Grifoni A, Sidney J, Vita R, Peters B, Crotty S, Weiskopf D, et al. SARS-CoV-2 human T cell epitopes: Adaptive immune response against COVID-19. Cell Host Microbe. 2021;29(7):1076-92.  https://doi.org/10.1016/j.chom.2021.05.010  PMID: 34237248 
  29. Gilbert PB, Montefiori DC, McDermott AB, Fong Y, Benkeser D, Deng W, et al. Immune correlates analysis of the mRNA-1273 COVID-19 vaccine efficacy clinical trial. Science. 2022;375(6576):43-50.  https://doi.org/10.1126/science.abm3425  PMID: 34812653 
  30. Stærke NB, Reekie J, Nielsen H, Benfield T, Wiese L, Knudsen LS, et al. Levels of SARS-CoV-2 antibodies among fully vaccinated individuals with Delta or Omicron variant breakthrough infections. Nat Commun. 2022;13(1):4466.  https://doi.org/10.1038/s41467-022-32254-8  PMID: 35915081 
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