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Antibody titers and breakthrough infections with Omicron SARS-CoV-2

Published:February 03, 2022DOI:https://doi.org/10.1016/j.jinf.2022.01.044
      Dear Editor,
      Recent studies indicated that the strong immune evasion potential of the most recent SARS-CoV-2 variant, Omicron, results in more frequent reinfections and breakthrough infections despite the widespread delivery of mRNA vaccine booster doses .
      • Kuhlmann C.
      • Konstanze Mayer C.
      • Claassen M.
      • Maponga T.
      • Burgers W.A.
      • Keeton R.
      Breakthrough infections with SARS-CoV-2 omicron despite mRNA vaccine booster dose.
      ,
      • Lu L.
      • Mok B.W.
      • Chen L.L.
      • Chan J.M.
      • Tsang O.T.
      • Lam B.H.
      • et al.
      Neutralization of SARS-CoV-2 Omicron variant by sera from BNT162b2 or Coronavac vaccine recipients.
      Antispike antibody titers greater than 141 binding antibody units (BAU) per milliliter are correlated with the presence of neutralizing antibodies (the most widely accepted marker of protection) against wild-type virus and the Alpha variant,
      • Dimeglio C.
      • Herin F.
      • Martin-Blondel G.
      • Miedougé M.
      • Izopet J.
      Antibody titers and protection against a SARS-CoV-2 infection.
      but neutralization of the Delta and Omicron variants probably requires higher antibody titers. Recent results showed that there was evidence of significant waning of antibody reactivity against Delta and Omicron six months after the second dose of vaccine.
      • Faustini S.
      • Shields A.
      • Banham G.
      • Wall N.
      • Al-Taei S.
      • Tanner C.
      • et al.
      Cross reactivity of spike glycoprotein induced antibody against delta and omicron variants before and after third SARS-CoV-2 vaccine dose in healthy and immunocompromised individuals.
      In this complementary study, we compared the concentrations of binding antibodies before breakthrough infections with Delta or Omicron SARS-CoV-2 variants.
      We measured the antibody titers in 1169 vaccinated individuals shortly before their breakthrough infection with the Omicron SARS-CoV-2 variant (1 November – 31 December 2021). Total SARS-CoV-2 antibodies were measured with a quantitative enzyme-linked immunosorbent assay (ELISA) (Wantai Biological Pharmacy Enterprise Co., Ltd, China).
      • Chapuy-Regaud S.
      • Miédougé M.
      • Abravanel F.
      • Da Silva I.
      • Porcheron M.
      • Fillaux J.
      • et al.
      Evaluation of three quantitative anti-SARS-CoV-2 antibody immunoassays.
      Symptomatic and asymptomatic infections were detected between 15 November 2021 and 12 January 2022 using a nucleic-acid amplification method (Aptima™ SARS-CoV-2 assay, Panther™ system, Hologic, USA).
      • Trémeaux P.
      • Lhomme S.
      • Abravanel F.
      • et al.
      Evaluation of the Aptima™ transcription-mediated amplification assay (Hologic®) for detecting SARS-CoV-2 in clinical specimens.
      Viral genotyping was performed using Pacific Biosciences Technology.
      • Lhomme S.
      • Latour J.
      • Jeanne N.
      • Trémeaux P.
      • Ranger N.
      • Migueres M.
      • et al.
      Prediction of SARS-CoV-2 variant lineages using the S1-encoding region sequence obtained by pacbio single-molecule real-time sequencing.
      We matched for age, gender and vaccination status (1, 2 or 3 doses) each Omicron-infected individual with a person infected with the Delta variant identified between September 1 and December 1, 2021 for whom we had a total antibody titer 15 days to 2 months before infection. The antibody concentrations at the time of infection were estimated with an exponential decay model.
      • Dimeglio C.
      • Herin F.
      • Da-Silva I.
      • Porcheron M.
      • Martin-Blondel G.
      • Chapuy-Regaud S.
      • Izopet J.
      Post-vaccination SARS-CoV-2 antibody kinetics and protection duration.
      These analyses were part of the national SARS-CoV-2 surveillance. French law (CSP Art.L1121–1.1) does not require institutional review board approval for anonymous non-interventional studies.
      The median age of the 1169 individuals (602; 51.5 males) was 45 years (interquartile range [IQR] 29–71). 258 (22.1%) had been given one, 859 (73.5%) two, and 52 (4.4%) three doses of mRNA vaccine. The ELISA analyses indicated that 90% of the Omicron infections occurred in people whose total antibody concentration was less than or equal to 6967 BAU/ml. In contrast, 90% of the Delta infections involved people with binding antibody concentrations below 2905 BAU/ml (Fig. 1, p<0.01, Wilcoxon signed rank test).
      Fig. 1
      Fig. 1: Distributions of binding antibody concentrations before infection with Delta or Omicron Sars-CoV-2 variants.
      These figures suggest that infections with the Omicron SARS-CoV-2 variant can occur despite high binding antibody concentrations, even at concentrations 2.4 higher than infections with the Delta SARS-CoV-2 variant. This is consistent with a recent study indicating that a booster Pfizer dose as well as vaccination of previously infected individuals generated an anti-Omicron neutralizing response, with titers 6 - 23 times lower against Omicron than those against Delta.
      • Planas D.
      • Saunders N.
      • Maes P.
      • Guivel-Benhassine F.
      • Planchais C.
      • Buchrieser J.
      • Bolland W.H.
      • et al.
      Considerable escape of SARS-CoV-2 Omicron to antibody neutralization.
      This is also consistent with another study showing that the neutralization titers of anti-Omicron antibodies in the serum of plasma donors were 17 to 22 times lower than they are against the Delta variant.

      Aggarwal, A. et al. SARS-Cov-2 Omicron: evasion of potent humoral responses and resistance to clinical immunotherapeutics relative to viral variants of concern. medRxiv. doi: https://doi.org/10.1101/2021.12.14.21267772

      The antibody thresholds found in our study should be compared to those obtained in further studies on other populations.

      Declaration of Competing Interest

      The authors declare no conflict of interest

      Funding

      No specific funding

      Acknowledgments

      The English text was edited by Dr Owen Parkes.

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