key: cord-1030550-daxgylpu
authors: Terpos, Evangelos; Trougakos, Ioannis P.; Apostolakou, Filia; Charitaki, Ioanna; Sklirou, Aimilia D.; Mavrianou, Nefeli; Papanagnou, Eleni‐Dimitra; Liacos, Christine‐Ivy; Gumeni, Sentiljana; Rentziou, Gianna; Korompoki, Eleni; Papassotiriou, Ioannis; Dimopoulos, Meletios A.
title: Age‐dependent and gender‐dependent antibody responses against SARS‐CoV‐2 in health workers and octogenarians after vaccination with the BNT162b2 mRNA vaccine
date: 2021-04-24
journal: Am J Hematol
DOI: 10.1002/ajh.26185
sha: 58aa01c0f42817b4c29af22e601c879a068ae751
doc_id: 1030550
cord_uid: daxgylpu

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Age-dependent and genderdependent antibody responses against SARS-CoV-2 in health workers and octogenarians after vaccination with the BNT162b2 mRNA vaccine To the Editor:

Efficacy of vaccines against SARS-CoV-2 virus is of great importance to mitigate the Covid-19 pandemic. 1 The BNT162b2 mRNA vaccine (Comirnaty) is the first approved by both FDA and EMA, due to its efficacy in apparently healthy adults. 2 Recently, an assessment of the first vaccination dose effects among nursing facility residents and staff showed that there is some protection after the first injection. 3 Here we present the kinetics of anti-SARS-CoV-2 Spike-Receptor Binding Domain (RBD) IgGs and SARS-CoV-2 neutralizing antibodies (NAbs) development in health workers and octogenarians, who participated in a prospective study (NCT04743388) studying the efficacy of vaccination for the prevention of Covid-19.

Major inclusion criteria for participation in this study included: Anti-Spike-RBD IgG antibodies (representing response to either prior infection or vaccine) and NAbs against SARS-CoV-2 were measured using FDA approved methods, that is, the Elecsys Anti-SARS-CoV-2 S assay (Roche Diagnostics GmbH, Mannheim, Germany) and the cPas SARS-CoV-2 NAbs Detection Kit Whereas, from group two, one (0.89%) was positive for anti-Spike-RBD IgGs and 10 (8.92%) for Nabs. All participants who were positive for anti-Spike-RBD IgGs on D1 were positive for NAbs; interestingly, positivity for NAbs did not always correlate with increased anti-Spike-RBD IgGs titers (data not shown) indicating the existence of NAbs to distinct non-RBD epitopes on the Spike protein. 5 Also, in agreement to recent findings, 6 IgGs was less prominent for ages 51-70 years vs 25-50 years on D22 and D36 and significantly less pronounced (vs other age groups) for octogenarians on D22 and D50 ( Figure 1A 1 ). This age-dependent pattern of immune responses was likewise evident for NAbs on D22 and D50 by comparing individuals aged 25-50 vs 51-70 years, and for both age groups vs octogenarians ( Figure 1B) .

Interestingly, the anti-Spike-RBD IgGs titer on D22 were higher in females vs males in octogenarians (Figure 1A 2 ) ; a trend for more robust female anti-Spike-RBD immune responses was also observed in the other age groups. Similarly, NAbs' titers were found higher in females vs males in octogenarians on both D22 and D50 ( Figure 1B) .

We conclude that the BNT162b2 mRNA vaccine is particularly effective in producing high anti-SARS-CoV-2 anti-RBD IgGs and NAbs titers in healthy individuals with no presence of active malignancy, autoimmune disease under immunosuppressive therapy or end-stage renal dysfunction. Interestingly, this humoral immune response is agedependent and gender-dependent (especially at octogenarians); it peaks at the highest level (independently of age or gender) 2 weeks post D22 (second dose) and starts to decline (also independently of age or gender) 4 weeks post D22. Our data also support an increased production of anti-RBD IgGs and NAbs titers after the first dose, which is similarly more robust in younger ages and in female octogenarians. These findings indicate that the second timely vaccination is critical, especially in the elderly population. Given its 18 months duration, age stratification, demographics, and combined Abs assays, our on-going study has the potential to provide critical information on the duration of the BNT162b2 mRNA vaccine-mediated protection.

Insights to SARS-CoV-2 life cycle, pathophysiology, and rationalized treatments that target COVID-19 clinical complications

Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine

First-dose COVID-19 vaccination coverage among skilled nursing facility residents and staff

A SARS-CoV-2 surrogate virus neutralization test based on antibody-mediated blockage of ACE2-spike protein-protein interaction

Isolation of potent SARS-CoV-2 neutralizing antibodies and protection from disease in a small animal model

Binding and neutralization antibody titers after a single vaccine dose in health care workers previously infected with SARS-CoV-2

We thank Tina Bagratuni, PhD, Dimitrios Patseas, PhD, Mrs Nikoletta-Aikaterini Kokkali and Mrs Stamatia Skourti for administrative, technical, and/or material support. We also thank Roche Diagnostics GmbH