Antibody-Mediated Immunogenicity Against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Following Priming, Boosting, and Hybrid Immunity: Insights From 11 Months of Follow-up of a Healthcare Worker Cohort in Israel, December 2020-October 2021

Michael Edelstein, Karine Wiegler Beiruti, Hila Ben-Amram, Naor Bar-Zeev, Christian Sussan, Hani Asulin, David Strauss, Younes Bathish, Salman Zarka, Kamal Abu Jabal

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND: We determined circulating anti-S severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin G (IgG) antibody titers in a vaccinated healthcare workers (HCWs) cohort from Northern Israel in the 11 months following primary vaccination according to age, ethnicity, and previous infection status. METHODS: All consenting HCWs were invited to have their IgG levels measured before vaccination and at 6 subsequent timepoints using a quantitative S1/S2 IgG assay. All HCWs with suspected coronavirus disease 2019 (COVID-19) were polymerase chain reaction (PCR) tested. We described trends in circulating IgG geometric mean concentration (GMC) by age, ethnicity, timing of boosting, and previous infection status and compared strata using Kruskall-Wallis tests. RESULTS: Among 985 vaccinated HCWs, IgG titers between 1 month post 2nd dose to pre-boosting gradually decreased in all age groups. Younger or previously infected individuals had higher initial post-vaccination IgG levels (P < .001 in both cases); differences substantially decreased or disappeared at 7-9 months, before boosting. The proportion of individuals infected prior to initiating vaccination and re-infected after dose 1 was comparable to the proportion of breakthrough infection post-dose 2 in those not previously infected (4.2 vs 4.7%). Pre-infection IgG levels in the 40 participants with breakthrough infection after dose 2 were similar to levels measured at the same timepoint in vaccinated HCWs who remained uninfected (P > .3). Post-dose3 IgG levels were more than 10-fold those 1 month post-dose 2. CONCLUSIONS: Immunity waned in all age groups and previously infected individuals, reversed by boosting. IgG titers decrease and reinfections in individuals with hybrid immunity (infection + vaccination) suggests they may also require further doses. Our study also highlights the difficulty in determining protective IgG levels.

Original languageEnglish
Pages (from-to)e572-e578
JournalClinical Infectious Diseases
Volume75
Issue number1
DOIs
StatePublished - 24 Aug 2022
Externally publishedYes

Bibliographical note

Funding Information:
Z.M. was supported by The Single Cell Gene Expression Atlas grant 108437/Z/15/Z from the Wellcome Trust. E.W. was supported by the French National Program Investissement d’Avenir (Labex NetRNA) administered by the Agence National de la Recherche (ANR-10-LABX-0036_NETRNA). Y.X. was supported by NSFC under Grant No. 31570722 and 11874162. M.S. and her group were supported by the Polish National Science Center (NCN; 2016/23/B/ST6/03931) and by the statutory funds of Poznan University of Technology, Poland. S-J.C was supported by NIH R01-GM117059 (S.-J.C) and NIH R01-GM063732 (S.-J.C). R.D. and his group were supported by NIH R35 GM122579 and R21 CA219847. D.M.J.L. group was funded by Cancer Research UK program grant A18604. R.T.B. and his group were funded by NIH R01-GM073850. J.M.B. and his group were supported by the Polish National Science Center (NCN; 2012/04/A/NZ2/ 00455 to J.M.B. and 2015/17/N/NZ2/03360 to M.M), and by the Foundation for Polish Science (FNP; POIR.04.04.00-00-3CF0/16). Support from the National Institutes for Health (5R01GM123247, 2R01 GM114015, and 1R35 GM134864 to N.V.D.) and the Passan Foundation are acknowledged. The project described was also supported by the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant UL1 TR002014 (J.W. and N.V.D.). Funding for the open access charge was provided by Shanghai Fourth People’s Hospital. The authors thank the Lee group at the Korea Institute for Advanced Study and an anonymous group for their participation in RNA-Puzzles. The authors also thank the members of the Bujnicki group for technical contributions, including Stanisław Dunin-Horkawicz (IIMCB), Grzegorz Chojnowski (IIMCB), Wayne Dawson (IIMCB), Dorota Matelska (IIMCB), Catarina Almeida (IIMCB), Bharat Madan (IIMCB), Grzegorz Lach (IIMCB). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Funding Information:
Z.M. was supported by The Single Cell Gene Expression Atlas grant 108437/Z/15/Z from the Wellcome Trust. E.W. was supported by the French National Program Investissement d'Avenir (Labex NetRNA) administered by the Agence National de la Recherche (ANR-10-LABX-0036_NETRNA). Y.X. was supported by NSFC under Grant No. 31570722 and 11874162. M.S. and her group were supported by the Polish National Science Center (NCN; 2016/23/B/ST6/03931) and by the statutory funds of Poznan University of Technology, Poland. S-J.C was supported by NIH R01-GM117059 (S.-J.C) and NIH R01-GM063732 (S.-J.C). R.D. and his group were supported by NIH R35 GM122579 and R21 CA219847. D.M.J.L. group was funded by Cancer Research UK program grant A18604. R.T.B. and his group were funded by NIH R01-GM073850. J.M.B. and his group were supported by the Polish National Science Center (NCN; 2012/04/A/NZ2/ 00455 to J.M.B. and 2015/17/N/NZ2/03360 to M.M), and by the Foundation for Polish Science (FNP; POIR.04.04.00-00-3CF0/16). Support from the National Institutes for Health (5R01GM123247, 2R01 GM114015, and 1R35 GM134864 to N.V.D.) and the Passan Foundation are acknowledged. The project described was also supported by the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant UL1 TR002014 (J.W. and N.V.D.). Funding for the open access charge was provided by Shanghai Fourth People's Hospital. The authors thank the Lee group at the Korea Institute for Advanced Study and an anonymous group for their participation in RNA-Puzzles. The authors also thank the members of the Bujnicki group for technical contributions, including Stanis?aw Dunin-Horkawicz (IIMCB), Grzegorz Chojnowski (IIMCB), Wayne Dawson (IIMCB), Dorota Matelska (IIMCB), Catarina Almeida (IIMCB), Bharat Madan (IIMCB), Grzegorz Lach (IIMCB). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Author contributions: E.W. conceived and supervised the project, coordinated the collaboration, and wrote the manuscript. Z.M. organized the prediction, analyzed the results, built the website, and wrote the manuscript. All other authors predicted the structures, analyzed the results, and wrote the manuscript.

Publisher Copyright:
© The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America.

Keywords

  • COVID-19
  • Israel
  • SARS-CoV-2
  • vaccine immunogenicity
  • vaccines

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

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