The Anti-SARS-CoV-2 IgG1 and IgG3 Antibody Isotypes with Limited Neutralizing Capacity against Omicron Elicited in a Latin Population a Switch toward IgG4 after Multiple Doses with the mRNA Pfizer–BioNTech Vaccine
Abstract
:1. Introduction
2. Materials and Methods
2.1. Antigen and Reagents
2.2. Study Cohorts
2.3. Ethical Statement
2.4. Detection of Anti-SARS-CoV-2 IgG Antibodies
2.5. Detection of SARS-CoV-2 IgG Subclasses
2.6. Neutralization Assay
2.7. Statistical Analysis
3. Results and Discussion
3.1. Assessment of In-House IgG and IgG Isotype ELISA Performance
3.2. The Antibody Response in Unvaccinated Convalescent COVID-19 Subjects Is Dominated by IgG1 and IgG3 Isotypes, Which Neutralize the Wild-Type Strain and the Alpha and Delta VOCs but Are Poorly Effective against Omicron
3.3. The Antibody Response in Previously Infected Subjects That Received Two Doses of the Pfizer–BioNTech or Moderna-1273 Vaccine Is Dominated by the IgG1 Isotype Which Has Potent Neutralizing Activity against the Alpha, Delta, and Omicron VOCs
3.4. Class Switch toward IgG4 Occurs in Subjects That Receive Multiple Doses of Pfizer–BioNTech Vaccine, Which Is Sustained over the Time
3.5. Switch in Class toward IgG4 Is Also Observed in Subjects with Inflammatory Bowel Disease and Received Multiple Vaccinations
4. Limitations of the Study
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Cohort-1: SARS-CoV-2 infected; convalescent not vaccinated. | |
Date of Collection | 26 April 2020 to 5 June 2020 |
Number of specimens | 85 (31 sera and 54 plasma) |
Time after infection (gap elapsed between the date of the confirmatory RT-qPCR test and the sampling date) | |
Range | 0 to 139 days |
Median | 35.5 days |
Number specimens with 0–30 days after infection. | 26 |
Median | 22 days |
Number specimens with 31–60 days after infection | 32 |
Median | 37.5 days |
Number specimens with >60 days after infection. | 11 |
Median | 84 days |
Unknown | 16 |
Cohort-5: Pre-Pandemic Samples | |
Subjects with unknown health status | |
Collection date | 2012 |
Number included | 78 (Sera) |
Other respiratory/viral infections | |
Collection date | 2018 to 2019 |
Number included | 47 (Sera) |
Respiratory allergies | 13 |
Zika virus | 5 |
Dengue virus | 5 |
Influenza A/B | 12 |
Respiratory Syncytial Virus | 6 |
Mycoplasma | 6 |
Cohort-2: Serial samples from previously SARS-CoV-2 infected subjects that received two doses of mRNA vaccine (Pfizer-BioNTech or Moderna-1273). | |
Number of subjects | 12 |
Sex | 7 female and 5 males |
Date of collection | 27 October 2020 to 20 September 2021 |
Number of specimens | 36 |
Sample 1 (Baseline) | Days after infection |
Range | |
Median | |
Sample 2 | Days after the 2nd dose |
Range | 15 to 32 days |
Median | 21.5 |
Sample 3 | Days after the 2nd dose |
Range | 74 to 169 days |
Median | 96 |
Cohort-3a: Serial samples from no previous SARS-CoV-2 infected subjects that received multiple Pfizer-BioNTech vaccinations. | |
Number of subjects | 4 |
Sex | 3 female and 1 male |
Date of collection | 10 August 2020 to10 August 2023 |
Number of specimens | 26 |
Sample 1 (baseline) | Previous 1st dose |
Sample 2 | Days after the 2nd dose |
Range | 19 to 35 days |
Median | 20 |
Sample 3 | Days after the 3rd dose |
Range | 31 to 43 days |
Median | 31 |
Sample 4 | Days after the 3rd dose |
Range | 180 to 420 days |
Median | 255 |
Sample 5 | Days after bivalent vaccine |
Median | 30 days |
Sample 6 | Days after bivalent vaccine |
Range | 90–180 days |
Median | 180 |
Cohort-3b: Single sample from no previous SARS-CoV-2 infection multiple Pfizer-BioNTech vaccinations, collected ~2 years after the last dose. | |
Number of subjects | 8 |
Sex | 4 female and 4 males |
Number of specimens | 8 |
Date of sample collection | 3 August 2023 to 23 October 2023 |
Date of last vaccination (3rd dose or bivalent) | 30 September 2021 to 28 December 2021 |
Sample 1 | Days after the 3rd dose |
Range | 351 to 723 days |
Median | 634 |
Cohort-4: Serial samples from no-previous SARS-CoV-2 infected subjects with inflammatory bowel disease (IBD) that received three doses of mRNA vaccine (Pfizer). | |
Number of subjects | 6 |
Sex | 3 female and 3 males. |
Date of collection | 14 April 2021 to 22 July 2022 |
Number of specimens | 24 |
Sample 1 (baseline) | Days after 2nd dose |
Range | 15 to 28 days |
Median | 17 |
Sample 2 | Days after 3rd dose |
Median | 60 |
Sample 3 | Days after 3rd dose |
Median | 180 |
Antibody Class/Subclass | C-PASS Neutralization Test | |||
---|---|---|---|---|
Total IgG | WT | Alpha | Delta | Omicron |
| 98.87 | 75.29 | 69.41 | 3.529 |
| 0.661 | 0.056 | 0.049 | 0.00057 |
| Substantial agreement | Slight agreement | Slight agreement | No agreement |
IgG1 | ||||
| 76.47 | 72.94 | 57.64 | 24.70 |
| 0.050 | 0.268 | −0.038 | −0.016 |
| Slight agreement | Fair agreement | No agreement | No agreement |
IgG2 | ||||
| 9.41 | 31.76 | 34.88 | -- |
| 0.002 | 0.032 | −0.014 | No computed |
| No agreement | Slight agreement | No agreement | -- |
IgG3 | ||||
| 30.58 | 48.23 | 50.58 | 69.23 |
| 0.018 | 0.151 | 0.147 | 0.006 |
| Slight agreement | Slight agreement | Slight agreement | No agreement |
IgG4 | ||||
| 14.11 | 30.588 | 35.29 | -- |
| 0.0064 | 0.011 | −0.026 | No computed |
| No agreement | Slight agreement | No agreement | -- |
IgM | ||||
| 88.23 | 77.64 | 72.94 | 16.47 |
| 0.255 | 0.298 | 0.266 | 0.0078 |
| Fair agreement | Fair agreement | Fair agreement | No agreement |
IgA | ||||
| 40.00 | 55.29 | 48.23 | 64.19 |
| 0.028 | 0.205 | 0.050 | −0.002 |
| Slight agreement | Fair agreement | Slight agreement | No agreement |
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© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
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Espino, A.M.; Armina-Rodriguez, A.; Alvarez, L.; Ocasio-Malavé, C.; Ramos-Nieves, R.; Rodriguez Martinó, E.I.; López-Marte, P.; Torres, E.A.; Sariol, C.A. The Anti-SARS-CoV-2 IgG1 and IgG3 Antibody Isotypes with Limited Neutralizing Capacity against Omicron Elicited in a Latin Population a Switch toward IgG4 after Multiple Doses with the mRNA Pfizer–BioNTech Vaccine. Viruses 2024, 16, 187. https://doi.org/10.3390/v16020187
Espino AM, Armina-Rodriguez A, Alvarez L, Ocasio-Malavé C, Ramos-Nieves R, Rodriguez Martinó EI, López-Marte P, Torres EA, Sariol CA. The Anti-SARS-CoV-2 IgG1 and IgG3 Antibody Isotypes with Limited Neutralizing Capacity against Omicron Elicited in a Latin Population a Switch toward IgG4 after Multiple Doses with the mRNA Pfizer–BioNTech Vaccine. Viruses. 2024; 16(2):187. https://doi.org/10.3390/v16020187
Chicago/Turabian StyleEspino, Ana M., Albersy Armina-Rodriguez, Laura Alvarez, Carlimar Ocasio-Malavé, Riseilly Ramos-Nieves, Esteban I. Rodriguez Martinó, Paola López-Marte, Esther A. Torres, and Carlos A. Sariol. 2024. "The Anti-SARS-CoV-2 IgG1 and IgG3 Antibody Isotypes with Limited Neutralizing Capacity against Omicron Elicited in a Latin Population a Switch toward IgG4 after Multiple Doses with the mRNA Pfizer–BioNTech Vaccine" Viruses 16, no. 2: 187. https://doi.org/10.3390/v16020187