Long-term Decay of Anti-RBD IgG Titers After BNT162b2 Vaccination is Not Mirrored by Loss of Neutralizing Bioactivity Against SARS-CoV-2

Overview

Journal Clin Chim Acta

Specialty Biochemistry

Date 2021 Nov 29

PMID 34843705

Citations 15

Authors

Giacomo Malipiero

Pierlanfranco DAgaro

Ludovica Segat

Anna Moratto

Danilo Villalta

Affiliations

Soon will be listed here.

Abstract

Background And Aims: Long-term kinetics of anti-RBD IgG and neutralizing antibodies were analyzed in a cohort of COVID-19 naïve health care workers (HCW) undergoing SARS-CoV-2 vaccination.

Methods: An anti-RBD IgG immunoassay and a surrogate virus neutralization test (sVNT) were performed at different time points up to 6 months after vaccination in 57 HCWs. Values of anti-RBD IgG predicting an high neutralizing bioactivity (>60%) were also calculated.

Results: Mean (range) values of anti-RBD IgG were 294.7 (11.6-1554), 2583 (398-8391), 320.4 (42.3-1134) BAU/mL at T1 (21 days after the 1st dose [T0]), T2 (30 days after the 2nd dose) and T3 (+180 days after T0), respectively. Mean (range) percentages of neutralization (NS%) were 24 (0-76), 86 (59-96) and 82 (52-99) at T1, T2 and T3, respectively. Anti-RBD IgG values and NS% were positively correlated at T2 and T3 while anti-RBD IgG value predicting a NS% > 60 markedly differed at T2 and T3 (594 vs. 108 BAU/mL, respectively).

Conclusion: While a high neutralizing bioactivity was maintained at least 6 months after vaccination in almost all individuals, the mean values of anti-RBD-IgG showed a marked decline at 6 months. The absolute value of anti-RBD IgG is a poor marker of neutralizing bioactivity.

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References

Papenburg J, Cheng M, Corsini R, Caya C, Mendoza E, Manguiat K . Evaluation of a Commercial Culture-Free Neutralization Antibody Detection Kit for Severe Acute Respiratory Syndrome-Related Coronavirus-2 and Comparison With an Antireceptor-Binding Domain Enzyme-Linked Immunosorbent Assay. Open Forum Infect Dis. 2021; 8(6):ofab220. PMC: 8135688. DOI: 10.1093/ofid/ofab220. View

Bauer G . The variability of the serological response to SARS-corona virus-2: Potential resolution of ambiguity through determination of avidity (functional affinity). J Med Virol. 2020; 93(1):311-322. PMC: 7361859. DOI: 10.1002/jmv.26262. View

Peterhoff D, Gluck V, Vogel M, Schuster P, Schutz A, Neubert P . A highly specific and sensitive serological assay detects SARS-CoV-2 antibody levels in COVID-19 patients that correlate with neutralization. Infection. 2020; 49(1):75-82. PMC: 7441844. DOI: 10.1007/s15010-020-01503-7. View

Douxfils J, Gillot C, Mullier F, Favresse J . Post-SARS-CoV-2 vaccination specific antibody decrease - Thresholds for determining seroprevalence and seroneutralization differ. J Infect. 2021; 83(4):e4-e5. PMC: 8364678. DOI: 10.1016/j.jinf.2021.08.023. View

Stromer A, Rose R, Grobe O, Neumann F, Fickenscher H, Lorentz T . Kinetics of Nucleo- and Spike Protein-Specific Immunoglobulin G and of Virus-Neutralizing Antibodies after SARS-CoV-2 Infection. Microorganisms. 2020; 8(10). PMC: 7650537. DOI: 10.3390/microorganisms8101572. View

Sariol C, Pantoja P, Serrano-Collazo C, Rosa-Arocho T, Armina-Rodriguez A, Cruz L . Function Is More Reliable than Quantity to Follow Up the Humoral Response to the Receptor-Binding Domain of SARS-CoV-2-Spike Protein after Natural Infection or COVID-19 Vaccination. Viruses. 2021; 13(10). PMC: 8538099. DOI: 10.3390/v13101972. View

Goel R, Apostolidis S, Painter M, Mathew D, Pattekar A, Kuthuru O . Distinct antibody and memory B cell responses in SARS-CoV-2 naïve and recovered individuals following mRNA vaccination. Sci Immunol. 2021; 6(58). PMC: 8158969. DOI: 10.1126/sciimmunol.abi6950. View

Feng S, Phillips D, White T, Sayal H, Aley P, Bibi S . Correlates of protection against symptomatic and asymptomatic SARS-CoV-2 infection. Nat Med. 2021; 27(11):2032-2040. PMC: 8604724. DOI: 10.1038/s41591-021-01540-1. View

Hillus D, Schwarz T, Tober-Lau P, Vanshylla K, Hastor H, Thibeault C . Safety, reactogenicity, and immunogenicity of homologous and heterologous prime-boost immunisation with ChAdOx1 nCoV-19 and BNT162b2: a prospective cohort study. Lancet Respir Med. 2021; 9(11):1255-1265. PMC: 8360702. DOI: 10.1016/S2213-2600(21)00357-X. View

10.

Favresse J, Gillot C, Di Chiaro L, Eucher C, Elsen M, Van Eeckhoudt S . Neutralizing Antibodies in COVID-19 Patients and Vaccine Recipients after Two Doses of BNT162b2. Viruses. 2021; 13(7). PMC: 8309994. DOI: 10.3390/v13071364. View

11.

Michos A, Tatsi E, Filippatos F, Dellis C, Koukou D, Efthymiou V . Association of total and neutralizing SARS-CoV-2 spike -receptor binding domain antibodies with epidemiological and clinical characteristics after immunization with the 1 and 2 doses of the BNT162b2 vaccine. Vaccine. 2021; 39(40):5963-5967. PMC: 8302834. DOI: 10.1016/j.vaccine.2021.07.067. View

12.

Muecksch F, Weisblum Y, Barnes C, Schmidt F, Schaefer-Babajew D, Wang Z . Affinity maturation of SARS-CoV-2 neutralizing antibodies confers potency, breadth, and resilience to viral escape mutations. Immunity. 2021; 54(8):1853-1868.e7. PMC: 8323339. DOI: 10.1016/j.immuni.2021.07.008. View

13.

Bayart J, Douxfils J, Gillot C, David C, Mullier F, Elsen M . Waning of IgG, Total and Neutralizing Antibodies 6 Months Post-Vaccination with BNT162b2 in Healthcare Workers. Vaccines (Basel). 2021; 9(10). PMC: 8540417. DOI: 10.3390/vaccines9101092. View

14.

Rowntree L, Chua B, Nicholson S, Koutsakos M, Hensen L, Douros C . Robust correlations across six SARS-CoV-2 serology assays detecting distinct antibody features. Clin Transl Immunology. 2021; 10(3):e1258. PMC: 7916820. DOI: 10.1002/cti2.1258. View

15.

Pichler D, Baumgartner M, Kimpel J, Rossler A, Riepler L, Bates K . Marked Increase in Avidity of SARS-CoV-2 Antibodies 7-8 Months After Infection Is Not Diminished in Old Age. J Infect Dis. 2021; 224(5):764-770. PMC: 8195195. DOI: 10.1093/infdis/jiab300. View

16.

Angel Y, Spitzer A, Henig O, Saiag E, Sprecher E, Padova H . Association Between Vaccination With BNT162b2 and Incidence of Symptomatic and Asymptomatic SARS-CoV-2 Infections Among Health Care Workers. JAMA. 2021; 325(24):2457-2465. PMC: 8220476. DOI: 10.1001/jama.2021.7152. View

17.

Bauer G . The potential significance of high avidity immunoglobulin G (IgG) for protective immunity towards SARS-CoV-2. Int J Infect Dis. 2021; 106:61-64. PMC: 7944804. DOI: 10.1016/j.ijid.2021.01.061. View

18.

Addetia A, Crawford K, Dingens A, Zhu H, Roychoudhury P, Huang M . Neutralizing Antibodies Correlate with Protection from SARS-CoV-2 in Humans during a Fishery Vessel Outbreak with a High Attack Rate. J Clin Microbiol. 2020; 58(11). PMC: 7587101. DOI: 10.1128/JCM.02107-20. View

19.

Chia W, Zhu F, Ong S, Young B, Fong S, Bert N . Dynamics of SARS-CoV-2 neutralising antibody responses and duration of immunity: a longitudinal study. Lancet Microbe. 2021; 2(6):e240-e249. PMC: 7987301. DOI: 10.1016/S2666-5247(21)00025-2. View

20.

Savage H, Santos V, Edwards T, Giorgi E, Krishna S, Planche T . Prevalence of neutralising antibodies against SARS-CoV-2 in acute infection and convalescence: A systematic review and meta-analysis. PLoS Negl Trop Dis. 2021; 15(7):e0009551. PMC: 8291969. DOI: 10.1371/journal.pntd.0009551. View