Waning of IgG, Total and Neutralizing Antibodies 6 Months Post-Vaccination with BNT162b2 in Healthcare Workers

Abstract

Data about the long-term duration of antibodies after SARS-CoV-2 vaccination are still scarce and are important to design vaccination strategies. In this study, 231 healthcare professionals received the two-dose regimen of BNT162b2. Of these, 158 were seronegative and 73 were seropositive at baseline. Samples were collected at several time points. The neutralizing antibodies (NAbs) and antibodies against the nucleocapsid and the spike protein of SARS-CoV-2 were measured. At day 180, a significant antibody decline was observed in seronegative (−55.4% with total antibody assay; −89.6% with IgG assay) and seropositive individuals (−74.8% with total antibody assay; −79.4% with IgG assay). The estimated half-life of IgG from the peak humoral response was 21 days (95% CI: 13–65) in seronegative and 53 days (95% CI: 40–79) in seropositive individuals. The estimated half-life of total antibodies was longer and ranged from 68 days (95% CI: 54–90) to 114 days (95% CI: 87–167) in seropositive and seronegative individuals, respectively. The decline of NAbs was more pronounced (−98.6%) and around 45% of the subjects tested were negative at day 180. Whether this decrease correlates with an equivalent drop in the clinical effectiveness against the virus would require appropriate clinical studies.

Dynamics of Neutralizing Antibody Responses Following Natural SARS-CoV-2 Infection and Correlation with Commercial Serologic Tests. A Reappraisal and Indirect Comparison with Vaccinated Subjects

“…Having these data in mind, it is difficult to definitely conclude that these tests showed a better ability to detect NAbs than the other tests evaluated in this study [5]. In addition, our group and others previously showed that the positivity threshold reported in the instructions for using the Roche Elecsys ® anti-SARS-CoV-2 spike is not a threshold for correlating with neutralization [6][7][8][9][10][11]. It was demonstrated that higher antibody titers are needed to correlate with seroneutralization although this is subject to the diversity of antibody response among individuals [7,11].…”

Answer to the letter of Lippi & Plebani entitled “Not all SARS-CoV-2 IgG and neutralizing antibody assays are created equal”

“…Further on, all cited studies did not assess whether patients were infected by the Wuhan original strain or a variant strain, which, for the above reasons, could affect inter-assays harmonization. As to the study by Bayart et al [10] , which showed a much faster decline in neutralizing antibody titers using a live VNT than we assessed with our sVNT, available literature has so far provided contrasting results about long-term decay of circulating antibodies after mRNA vaccination, with some studies providing evidence for persistent and sustained neutralizing bioactivity of serum up to 6 months from vaccination [11] , [12] . It’s our opinion that such discrepancies are resulting from multiple factors, including but not limited to inter-assays inconsistencies, such as previous exposure to cross-reacting common cold coronaviruses, age, history of previous COVID-19, sex, and other comorbidities in vaccinated cohorts.…”

“…On the other hand, as repeatedly shown by comparative analyses in vaccinated cohorts [7] , [8] , [9] , the diagnostic reliability of sVNT seems to be retained when assessing vaccine-induced immune-responses, provided that the mRNA sequence of the vaccine RBD matches that of the recombinant RBD in the binding and competition assays. The cross-sectional studies cited by Lippi and Plebani [5] , [6] quantified humoral immunogenicity markers in two cohorts of convalescent COVID-19 patients while the cohort studied by Bayart et al [10] is as well affected by a large number (31%) of individuals with a positive serological scrutiny for SARS-CoV-2 infection before vaccination. In fact, the primary aim of the study by Meyer et al [5] was the diagnostic value and comparability of different immune assay platforms for a diagnosis of SARS-CoV-2 infection rather than the long-term monitoring of the immune response to a spike-based vaccine.…”

SARS-CoV-2 attack rate and population immunity in southern New England, March 2020 - May 2021

“…The most important information to integrate into the next phase of attack-rate estimation and population-immunity estimation in the US is the rate of antibody waning following SARS-CoV-2 infection and SARS-CoV-2 vaccination. Average waning rates are now known for the short-term post-infection [ 39 – 42 ] and post-vaccination [ 43 – 46 ][ 47 ], and this may be enough to estimate a recent attack rate [ 48 ] which can either be reported as such or chained together with other recent attack-rate estimates to provide an annual attack-rate estimate. Although the initial live integration of these data streams will no doubt be challenging, the benefit will be a situationally-aware susceptibility estimate that will allow us to evaluate the invasion ability of a new high-transmissibility variants (such as Alpha or Delta) or the inevitable immune-escape variants – like the Omicron lineage [ 49 , 50 ] – that will likely continue appearing in 2022 and 2023.…”