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Published in: Infection 6/2022

Open Access 11-04-2022 | Vaccination | Original Paper

Humoral immunity in dually vaccinated SARS-CoV-2-naïve individuals and in booster-vaccinated COVID-19-convalescent subjects

Authors: Vivian Glück, Leonid Tydykov, Anna-Lena Mader, Anne-Sophie Warda, Manuela Bertok, Tanja Weidlich, Christine Gottwald, Josef Köstler, Bernd Salzberger, Ralf Wagner, Michael Koller, André Gessner, Barbara Schmidt, Thomas Glück, David Peterhoff

Published in: Infection | Issue 6/2022

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Abstract

Background

The immune response to COVID-19-vaccination differs between naïve vaccinees and those who were previously infected with SARS-CoV-2. Longitudinal quantitative and qualitative serological differences in these two distinct immunological subgroups in response to vaccination are currently not well studied.

Methods

We investigate a cohort of SARS-CoV-2-naïve and COVID-19-convalescent individuals immediately after vaccination and 6 months later. We use different enzyme-linked immunosorbent assay (ELISA) variants and a surrogate virus neutralization test (sVNT) to measure IgG serum titers, IgA serum reactivity, IgG serum avidity and neutralization capacity by ACE2 receptor competition.

Results

Anti-receptor-binding domain (RBD) antibody titers decline over time in dually vaccinated COVID-19 naïves whereas titers in single dose vaccinated COVID-19 convalescents are higher and more durable. Similarly, antibody avidity is considerably higher among boosted COVID-19 convalescent subjects as compared to dually vaccinated COVID-19-naïve subjects. Furthermore, sera from boosted convalescents inhibited the binding of spike-protein to ACE2 more efficiently than sera from dually vaccinated COVID-19-naïve subjects.

Conclusions

Long-term humoral immunity differs substantially between dually vaccinated SARS-CoV-2-naïve and COVID-19-convalescent individuals. Booster vaccination after COVID-19 induces a more durable humoral immune response in terms of magnitude and quality as compared to two-dose vaccination in a SARS-CoV-2-naïve background.
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Literature
1.
go back to reference Tenforde MW, Self WH, Adams K, Gaglani M, Ginde AA, McNeal T, et al. Association between mRNA vaccination and COVID-19 hospitalization and disease severity. JAMA. 2021;326:2043.CrossRefPubMed Tenforde MW, Self WH, Adams K, Gaglani M, Ginde AA, McNeal T, et al. Association between mRNA vaccination and COVID-19 hospitalization and disease severity. JAMA. 2021;326:2043.CrossRefPubMed
3.
go back to reference Haas EJ, McLaughlin JM, Khan F, Angulo FJ, Anis E, Lipsitch M, et al. Infections, hospitalisations, and deaths averted via a nationwide vaccination campaign using the Pfizer–BioNTech BNT162b2 mRNA COVID-19 vaccine in Israel: a retrospective surveillance study. Lancet Infect Dis. 2021;22:357–66.CrossRefPubMedPubMedCentral Haas EJ, McLaughlin JM, Khan F, Angulo FJ, Anis E, Lipsitch M, et al. Infections, hospitalisations, and deaths averted via a nationwide vaccination campaign using the Pfizer–BioNTech BNT162b2 mRNA COVID-19 vaccine in Israel: a retrospective surveillance study. Lancet Infect Dis. 2021;22:357–66.CrossRefPubMedPubMedCentral
4.
go back to reference 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;27:2136–43.CrossRefPubMed 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;27:2136–43.CrossRefPubMed
5.
go back to reference Bergwerk M, Gonen T, Lustig Y, Amit S, Lipsitch M, Cohen C, et al. Covid-19 breakthrough infections in vaccinated health care workers. N Engl J Med. 2021;385:1474–84.CrossRefPubMed Bergwerk M, Gonen T, Lustig Y, Amit S, Lipsitch M, Cohen C, et al. Covid-19 breakthrough infections in vaccinated health care workers. N Engl J Med. 2021;385:1474–84.CrossRefPubMed
6.
go back to reference Glück V, Grobecker S, Tydykov L, Salzberger B, Glück T, Weidlich T, et al. SARS-CoV-2-directed antibodies persist for more than six months in a cohort with mild to moderate COVID-19. Infection. 2021;49:739–46.CrossRefPubMedPubMedCentral Glück V, Grobecker S, Tydykov L, Salzberger B, Glück T, Weidlich T, et al. SARS-CoV-2-directed antibodies persist for more than six months in a cohort with mild to moderate COVID-19. Infection. 2021;49:739–46.CrossRefPubMedPubMedCentral
9.
go back to reference Einhauser S, Peterhoff D, Niller HH, Beileke S, Günther F, Steininger P, et al. Spectrum bias and individual strengths of SARS-CoV-2 serological tests—a population-based evaluation. Diagnostics (Basel). 2021;11:1843.CrossRefPubMed Einhauser S, Peterhoff D, Niller HH, Beileke S, Günther F, Steininger P, et al. Spectrum bias and individual strengths of SARS-CoV-2 serological tests—a population-based evaluation. Diagnostics (Basel). 2021;11:1843.CrossRefPubMed
10.
go back to reference Peterhoff D, Glück V, Vogel M, Schuster P, Schütz A, Neubert P, et al. A highly specific and sensitive serological assay detects SARS-CoV-2 antibody levels in COVID-19 patients that correlate with neutralization. Infection. 2021;49:75–82.CrossRefPubMed Peterhoff D, Glück V, Vogel M, Schuster P, Schütz A, Neubert P, et al. A highly specific and sensitive serological assay detects SARS-CoV-2 antibody levels in COVID-19 patients that correlate with neutralization. Infection. 2021;49:75–82.CrossRefPubMed
11.
go back to reference Correa VA, Rodrigues TS, Portilho AI, de Trzewikoswki LG, De Gaspari E. Modified ELISA for antibody avidity evaluation: the need for standardization. Biomed J. 2021;44:433–8.CrossRefPubMed Correa VA, Rodrigues TS, Portilho AI, de Trzewikoswki LG, De Gaspari E. Modified ELISA for antibody avidity evaluation: the need for standardization. Biomed J. 2021;44:433–8.CrossRefPubMed
12.
go back to reference Girl P, Zwirglmaier K, von Buttlar H, Wölfel R, Müller K. Evaluation of two rapid lateral flow tests and two surrogate ELISAs for the detection of SARS-CoV-2 specific neutralizing antibodies. SSRN Journal. 2021. https://www.ssrn.com/abstract=3963559. Accessed 23 Jan 2022. Girl P, Zwirglmaier K, von Buttlar H, Wölfel R, Müller K. Evaluation of two rapid lateral flow tests and two surrogate ELISAs for the detection of SARS-CoV-2 specific neutralizing antibodies. SSRN Journal. 2021. https://​www.​ssrn.​com/​abstract=​3963559. Accessed 23 Jan 2022.
13.
go back to reference Shalash AO, Azuar A, Madge HYR, Modhiran N, Amarilla AA, Liang B, et al. Detection and quantification of SARS-CoV-2 receptor binding domain neutralization by a sensitive competitive ELISA assay. Vaccines. 2021;9:1493.CrossRefPubMedPubMedCentral Shalash AO, Azuar A, Madge HYR, Modhiran N, Amarilla AA, Liang B, et al. Detection and quantification of SARS-CoV-2 receptor binding domain neutralization by a sensitive competitive ELISA assay. Vaccines. 2021;9:1493.CrossRefPubMedPubMedCentral
15.
go back to reference England CG, Ehlerding EB, Cai W. NanoLuc: a small luciferase is brightening up the field of bioluminescence. Bioconjugate Chem. 2016;27:1175–87.CrossRef England CG, Ehlerding EB, Cai W. NanoLuc: a small luciferase is brightening up the field of bioluminescence. Bioconjugate Chem. 2016;27:1175–87.CrossRef
16.
17.
go back to reference 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;27:2032–40.CrossRefPubMedPubMedCentral 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;27:2032–40.CrossRefPubMedPubMedCentral
18.
go back to reference 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;39:4423–8.CrossRefPubMedPubMedCentral 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;39:4423–8.CrossRefPubMedPubMedCentral
19.
go back to reference 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;27:1205–11.CrossRefPubMed 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;27:1205–11.CrossRefPubMed
20.
go back to reference Levin EG, Lustig Y, Cohen C, Fluss R, Indenbaum V, Amit S, et al. Waning immune humoral response to BNT162b2 Covid-19 vaccine over 6 months. N Engl J Med. 2021;385: e84.CrossRefPubMed Levin EG, Lustig Y, Cohen C, Fluss R, Indenbaum V, Amit S, et al. Waning immune humoral response to BNT162b2 Covid-19 vaccine over 6 months. N Engl J Med. 2021;385: e84.CrossRefPubMed
22.
go back to reference Al-Sadeq DW, Shurrab FM, Ismail A, Amanullah FH, Thomas S, Aldewik N, et al. Comparison of antibody immune responses between BNT162b2 and mRNA-1273 SARS-CoV-2 vaccines in naïve and previously infected individuals. J Travel Med. 2021;28:taab190.CrossRefPubMed Al-Sadeq DW, Shurrab FM, Ismail A, Amanullah FH, Thomas S, Aldewik N, et al. Comparison of antibody immune responses between BNT162b2 and mRNA-1273 SARS-CoV-2 vaccines in naïve and previously infected individuals. J Travel Med. 2021;28:taab190.CrossRefPubMed
23.
go back to reference Gray AN, Martin-Blais R, Tobin NH, Wang Y, Brooker SL, Li F, et al. Humoral responses to SARS-CoV-2 mRNA vaccines: role of past infection. Nasrallah GK, editor. PLoS One. 2021;16: e0259703.CrossRefPubMedPubMedCentral Gray AN, Martin-Blais R, Tobin NH, Wang Y, Brooker SL, Li F, et al. Humoral responses to SARS-CoV-2 mRNA vaccines: role of past infection. Nasrallah GK, editor. PLoS One. 2021;16: e0259703.CrossRefPubMedPubMedCentral
24.
go back to reference Tang J, Grubbs G, Lee Y, Huang C, Ravichandran S, Forgacs D, et al. Antibody affinity maturation and cross-variant activity following SARS-CoV-2 mRNA vaccination: impact of prior exposure and sex. EBioMedicine. 2021;74:103748.CrossRefPubMedPubMedCentral Tang J, Grubbs G, Lee Y, Huang C, Ravichandran S, Forgacs D, et al. Antibody affinity maturation and cross-variant activity following SARS-CoV-2 mRNA vaccination: impact of prior exposure and sex. EBioMedicine. 2021;74:103748.CrossRefPubMedPubMedCentral
25.
go back to reference Löfström E, Eringfält A, Kötz A, Wickbom F, Tham J, Lingman M, et al. Dynamics of IgG-avidity and antibody levels after Covid-19. J Clin Virol. 2021;144:104986.CrossRefPubMedPubMedCentral Löfström E, Eringfält A, Kötz A, Wickbom F, Tham J, Lingman M, et al. Dynamics of IgG-avidity and antibody levels after Covid-19. J Clin Virol. 2021;144:104986.CrossRefPubMedPubMedCentral
26.
go back to reference Scheiblauer H, Nübling CM, Wolf T, Khodamoradi Y, Bellinghausen C, Sonntagbauer M, et al. Antibody response to SARS-CoV-2 for more than one year—kinetics and persistence of detection are predominantly determined by avidity progression and test design. J Clin Virol. 2022;146:105052.CrossRefPubMed Scheiblauer H, Nübling CM, Wolf T, Khodamoradi Y, Bellinghausen C, Sonntagbauer M, et al. Antibody response to SARS-CoV-2 for more than one year—kinetics and persistence of detection are predominantly determined by avidity progression and test design. J Clin Virol. 2022;146:105052.CrossRefPubMed
27.
go back to reference Abu-Raddad LJ, Chemaitelly H, Ayoub HH, Yassine HM, Benslimane FM, Al Khatib HA, et al. Association of prior SARS-CoV-2 infection with risk of breakthrough infection following mRNA vaccination in Qatar. JAMA. 2021;326:1930.CrossRefPubMed Abu-Raddad LJ, Chemaitelly H, Ayoub HH, Yassine HM, Benslimane FM, Al Khatib HA, et al. Association of prior SARS-CoV-2 infection with risk of breakthrough infection following mRNA vaccination in Qatar. JAMA. 2021;326:1930.CrossRefPubMed
29.
go back to reference Koutsakos M, Lee WS, Wheatley AK, Kent SJ, Juno JA. T follicular helper cells in the humoral immune response to SARS-CoV-2 infection and vaccination. J Leukoc Biol. 2021;111:355–65.CrossRefPubMed Koutsakos M, Lee WS, Wheatley AK, Kent SJ, Juno JA. T follicular helper cells in the humoral immune response to SARS-CoV-2 infection and vaccination. J Leukoc Biol. 2021;111:355–65.CrossRefPubMed
30.
go back to reference Neidleman J, Luo X, McGregor M, Xie G, Murray V, Greene WC, et al. mRNA vaccine-induced T cells respond identically to SARS-CoV-2 variants of concern but differ in longevity and homing properties depending on prior infection status. Elife. 2021;10: e72619.CrossRefPubMedPubMedCentral Neidleman J, Luo X, McGregor M, Xie G, Murray V, Greene WC, et al. mRNA vaccine-induced T cells respond identically to SARS-CoV-2 variants of concern but differ in longevity and homing properties depending on prior infection status. Elife. 2021;10: e72619.CrossRefPubMedPubMedCentral
31.
go back to reference Bozio CH, Grannis SJ, Naleway AL, Ong TC, Butterfield KA, DeSilva MB, et al. Laboratory-confirmed COVID-19 among adults hospitalized with COVID-19-like illness with infection-induced or mRNA vaccine-induced SARS-CoV-2 immunity—Nine States, January–September 2021. MMWR Morb Mortal Wkly Rep. 2021;70:1539–44.CrossRefPubMedPubMedCentral Bozio CH, Grannis SJ, Naleway AL, Ong TC, Butterfield KA, DeSilva MB, et al. Laboratory-confirmed COVID-19 among adults hospitalized with COVID-19-like illness with infection-induced or mRNA vaccine-induced SARS-CoV-2 immunity—Nine States, January–September 2021. MMWR Morb Mortal Wkly Rep. 2021;70:1539–44.CrossRefPubMedPubMedCentral
Metadata
Title
Humoral immunity in dually vaccinated SARS-CoV-2-naïve individuals and in booster-vaccinated COVID-19-convalescent subjects
Authors
Vivian Glück
Leonid Tydykov
Anna-Lena Mader
Anne-Sophie Warda
Manuela Bertok
Tanja Weidlich
Christine Gottwald
Josef Köstler
Bernd Salzberger
Ralf Wagner
Michael Koller
André Gessner
Barbara Schmidt
Thomas Glück
David Peterhoff
Publication date
11-04-2022
Publisher
Springer Berlin Heidelberg
Published in
Infection / Issue 6/2022
Print ISSN: 0300-8126
Electronic ISSN: 1439-0973
DOI
https://doi.org/10.1007/s15010-022-01817-8

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