Comparison of SARS-CoV-2 Antibody Response by Age Among Recipients of the BNT162b2 vs the mRNA-1273 Vaccine | Infectious Diseases | JAMA Network Open | JAMA Network
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Figure.  Levels of IgG to SARS-CoV-2 Spike RBD in an Employee Vaccine Cohort
Levels of IgG to SARS-CoV-2 Spike RBD in an Employee Vaccine Cohort

Preboost is 14 to 28 days after the primary immunization and postboost is 7 to 31 days after the boost immunization. Data are presented as geometric means with 95% CI and comparisons with Mann-Whitney U test. The dotted lines denotes cutoff of assay, as previously described.3 Accounting for multiple comparisons, P < .0125 was considered as significant.

aP < .001.

bP < .05.

Table.  Characteristics of Vaccinated Study Population
Characteristics of Vaccinated Study Population
1.
Polack  FP, Thomas  SJ, Kitchin  N,  et al; C4591001 Clinical Trial Group.  Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine.   N Engl J Med. 2020;383(27):2603-2615. doi:10.1056/NEJMoa2034577PubMedGoogle ScholarCrossref
2.
Baden  LR, El Sahly  HM, Essink  B,  et al; COVE Study Group.  Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine.   N Engl J Med. 2021;384(5):403-416. doi:10.1056/NEJMoa2035389PubMedGoogle ScholarCrossref
3.
Keshavarz  B, Wiencek  JR, Workman  LJ,  et al.  Quantitative measurement of IgG to severe acute respiratory syndrome coronavirus-2 proteins using ImmunoCAP.   Int Arch Allergy Immunol. 2021;182(5):417-424. doi:10.1159/000514203PubMedGoogle ScholarCrossref
4.
Müller  L, Andrée  M, Moskorz  W,  et al.  Age-dependent immune response to the Biontech/Pfizer BNT162b2 COVID-19 vaccination.   Clin Infect Dis. 2021;ciab381. doi:10.1093/cid/ciab381PubMedGoogle Scholar
5.
Abu Jabal  K, Ben-Amram  H, Beiruti  K,  et al.  Impact of age, ethnicity, sex and prior infection status on immunogenicity following a single dose of the BNT162b2 mRNA COVID-19 vaccine: real-world evidence from healthcare workers, Israel, December 2020 to January 2021.   Euro Surveill. 2021;26(6):2100096. doi:10.2807/1560-7917.ES.2021.26.6.2100096PubMedGoogle Scholar
6.
Wajnberg  A, Amanat  F, Firpo  A,  et al.  Robust neutralizing antibodies to SARS-CoV-2 infection persist for months.   Science. 2020;370(6521):1227-1230. doi:10.1126/science.abd7728PubMedGoogle ScholarCrossref
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    Research Letter
    Infectious Diseases
    September 2, 2021

    Comparison of SARS-CoV-2 Antibody Response by Age Among Recipients of the BNT162b2 vs the mRNA-1273 Vaccine

    Author Affiliations
    • 1Division of Allergy and Clinical Immunology, University of Virginia, Charlottesville
    JAMA Netw Open. 2021;4(9):e2124331. doi:10.1001/jamanetworkopen.2021.24331
    Introduction

    Two COVID-19 mRNA vaccines, BNT162b2 (ie, Pfizer/BioNTech) and mRNA-1273 (ie, Moderna), were approved via the US Food and Drug Administration Emergency Use Authorization (FDA-EUA) for adults in December 2020. Both incorporate mRNA that encodes for the prefusion stabilized spike glycoprotein, use a prime-boost strategy, and have shown strong immunogenicity in preclinical and clinical studies.1,2 Although the 2 vaccines share similar features and both showed strong efficacy in clinical trials, there are formulation differences, and there has been little head-to-head evaluation of antibody responses. In this cohort study, we used a quantitative assay for IgG to SARS-CoV-2 spike-receptor binding protein to compare antibody responses in an employee cohort in which both BNT162b2 and mRNA-1273 were administered. We hypothesized that there could be differences in antibody levels elicited by the 2 vaccines and explored the effect of age on immunogenicity.

    Methods

    This cohort study was approved by the University of Virginia institutional review board. Written informed consent was provided. This study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline.

    Adults affiliated with the University of Virginia, the majority of whom were employed by the Health System, were recruited to participate in this study. The analysis included all individuals who received 2 doses of either BNT162b2 or mRNA-1273 and had a blood sample drawn 7 to 31 days after the second vaccine (ie, postboost). Of note, the vaccine that was received depended on local availability. Some recipients also had a baseline (ie, within 7 days prior to the first vaccine) or preboost (ie, 14-28 days after the first vaccine but preceding the second vaccine) blood sample collected. Serum was isolated and IgG to SARS-CoV-2 spike RBD and nucleocapsid were measured with a quantitative ImmunoCAP-based system using a Phadia 250 (Thermo-Fisher/Phadia), as previously described.3 Statistical analysis was performed with GraphPad Prism 8 (GraphPad Software). Antibody levels were expressed by geometric mean with 95% CIs and comparisons were made between groups with the Mann-Whitney U test. To account for multiple comparisons, P < .0125 was considered significant. Additional methods are available in the Supplement. Statistical analysis was done in June 2021.

    Results

    The median age of the 167 recipients was 42 (interquartile range, 32-57 years), with 63 recipients (38%) aged 50 years or greater; 120 recipients (72%) were women (Table). There were no differences in age, sex, or race between those who received BNT162b2 (n = 79) or mRNA-1273 (n = 88). Only 6 (4%) of the participants had serologic evidence of prior COVID-19. Levels of IgG to SARS-CoV-2 spike RBD were lower in recipients of BNT162b2 as compared with mRNA-1273 at both the preboost blood draw (5.9 μg/mL [95% CI, 3.7-9.6 μg/mL] vs 19.1 μg/mL [95% CI, 15.8-23.1 μg/mL]) and postboost blood draw (45.9 μg/mL [95% CI, 37.0-57.0 μg/mL] vs 68.5 μg/mL [95% CI 61.9-75.7 μg/mL]) (Figure). Recipients aged 50 years and older who received BNT162b2 had preboost IgG levels (2.1 μg/mL [95% CI, 1.0-4.3 μg/mL]) that were lower than levels in recipients younger than 50 years who received BNT162b2 (10.2 μg/mL [95% CI, 6.0-17.5 μg/mL]) and also as compared with age-similar peers who received mRNA-1273 (14.7 μg/mL [95% CI, 10.0-21.2 μg/mL]) (Figure). Recipients aged 50 years and older who received BNT162b2 had postboost IgG levels (31.1 μg/mL [95% CI, 19.9-48.7 μg/mL]) that were lower than the levels in younger recipients of BNT162b2 (59.0 μg/mL [95% CI, 48.8-71.4 μg/mL]) and age-similar peers who received mRNA-1273 (71.8 μg/mL [95% CI, 58.1-88.8 μg/mL]) (Figure).

    Discussion

    In this cohort study, we used a quantitative assay and found that BNT162b2 elicited relatively lower antibody levels in older adults vs younger adults, which is consistent with emerging reports.4,5 By contrast, there was no difference in postboost antibody levels in older adults vs younger adults who received mRNA-1273. One explanation for the difference in immunogenicity observed in older adults could relate to the amount of mRNA used in the respective vaccines, with 30 μg contained in BNT162b2 and 100 μg in mRNA-1273.1,2 A limitation of this study is that the neutralizing antibodies were not measured; however, several groups have reported a strong correlation between SARS-CoV-2 binding and neutralizing antibodies.6 Additional studies are warranted to determine whether binding antibodies to SARS-CoV-2 can be used to predict clinical protection against COVID-19.

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    Article Information

    Accepted for Publication: June 29, 2021.

    Published: September 2, 2021. doi:10.1001/jamanetworkopen.2021.24331

    Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2021 Richards NE et al. JAMA Network Open.

    Corresponding Author: Jeffrey M. Wilson, MD, PhD, Division of Allergy and Clinical Immunology, University of Virginia, PO Box 801355, Charlottesville, VA, 22908 (jmw2gc@virginia.edu).

    Author Contributions: Dr Wilson had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Drs Richards and Keshavarz contributed equally.

    Concept and design: Richards, Keshavarz, Platts-Mills, Wilson.

    Acquisition, analysis, or interpretation of data: All authors.

    Drafting of the manuscript: Workman, Nelson, Platts-Mills, Wilson.

    Critical revision of the manuscript for important intellectual content: Richards, Keshavarz, Nelson, Platts-Mills.

    Statistical analysis: Keshavarz, Wilson.

    Obtained funding: Platts-Mills, Wilson.

    Administrative, technical, or material support: Richards, Workman, Nelson, Platts-Mills.

    Supervision: Richards, Platts-Mills, Wilson.

    Conflict of Interest Disclosures: Drs Platts-Mills and Wilson reported receiving assay support from Thermo-Fisher/Phadia outside the submitted work. Dr Wilson reported receiving consultancy fees from Thermo-Fisher/Phadia and funding for this project from the University of Virginia Manning COVID-19 Research Fund during the conduct of this study. Dr Wilson reported receiving ongoing salary support from AAAAI Faculty Development Award. No other disclosures were reported.

    Funding/Support: Dr Platts Mills was supported by grant R37-20565 from the National Institutes of Health.

    Role of the Funder/Sponsor: The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

    Additional Contributions: We thank all of the study participants.

    References
    1.
    Polack  FP, Thomas  SJ, Kitchin  N,  et al; C4591001 Clinical Trial Group.  Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine.   N Engl J Med. 2020;383(27):2603-2615. doi:10.1056/NEJMoa2034577PubMedGoogle ScholarCrossref
    2.
    Baden  LR, El Sahly  HM, Essink  B,  et al; COVE Study Group.  Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine.   N Engl J Med. 2021;384(5):403-416. doi:10.1056/NEJMoa2035389PubMedGoogle ScholarCrossref
    3.
    Keshavarz  B, Wiencek  JR, Workman  LJ,  et al.  Quantitative measurement of IgG to severe acute respiratory syndrome coronavirus-2 proteins using ImmunoCAP.   Int Arch Allergy Immunol. 2021;182(5):417-424. doi:10.1159/000514203PubMedGoogle ScholarCrossref
    4.
    Müller  L, Andrée  M, Moskorz  W,  et al.  Age-dependent immune response to the Biontech/Pfizer BNT162b2 COVID-19 vaccination.   Clin Infect Dis. 2021;ciab381. doi:10.1093/cid/ciab381PubMedGoogle Scholar
    5.
    Abu Jabal  K, Ben-Amram  H, Beiruti  K,  et al.  Impact of age, ethnicity, sex and prior infection status on immunogenicity following a single dose of the BNT162b2 mRNA COVID-19 vaccine: real-world evidence from healthcare workers, Israel, December 2020 to January 2021.   Euro Surveill. 2021;26(6):2100096. doi:10.2807/1560-7917.ES.2021.26.6.2100096PubMedGoogle Scholar
    6.
    Wajnberg  A, Amanat  F, Firpo  A,  et al.  Robust neutralizing antibodies to SARS-CoV-2 infection persist for months.   Science. 2020;370(6521):1227-1230. doi:10.1126/science.abd7728PubMedGoogle ScholarCrossref
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