key: cord-0882717-w38f6wni
authors: Douxfils, Jonathan; Gillot, Constant; Mullier, François; Favresse, Julien
title: Post-SARS-CoV-2 vaccination specific antibody decrease — Thresholds for determining seroprevalence and seroneutralization differ
date: 2021-08-15
journal: J Infect
DOI: 10.1016/j.jinf.2021.08.023
sha: 8c9c0a1d1af8efda279d6ce6bbbb21148e789cff
doc_id: 882717
cord_uid: w38f6wni

nan

(they) "would like to re-interpret these data in a more positive way by emphasizing the high antibody titers detected in this study". The authors then discussed on selected studies supporting their assumptions, even though we previously commented on the limitations of some of these studies to appreciate the antibody response due to inadequate sample dilution. (3) In our opinion, we did not convey "bad news" and as implied by the authors of this letter, we did not use deliberately "catchy" words. We factually interpreted and discussed the analytical results we obtained. In addition, our manuscript already stipulated that "it is important to notice that all participants still had a robust antibody response at 3 months". We also added that "moreover, the vaccination with BNT162b2 elicited much higher antibody titers at 3 months compared to the titers collected in serum from convalescent patients using the same assay". (2) An interim analysis of 75 out of the 231 subjects included in the CRO-Vax HCP study (4) reports a decline of 51% and 20% between day 90 and day 180 for the seronegative and seropositive groups, respectively.

We also noticed that the authors stipulate that the upper positive threshold of the test (without using sample dilution) is already 300-fold higher than the positivity threshold (i.e. 0.8 IU/mL) and seems to use this argument to support their optimistic view on the observed declined in antibody titers. We question on the relevance of such interpretation since the threshold of 0.8 IU/mL has not been determined against the neutralizing capacity but against positive RT-PCR to detect subjects who have been in contact with the virus. According to the manufacturer, a higher threshold is needed to correlate the Roche RBD total antibody assay (Roche Diagnostics, Machelen, Belgium) with the neutralizing capacity. (5) We take the opportunity of this response to report results showing that even high antibody titers as detected by the Roche RBD total antibody assay may not be neutralizing. Neutralizing antibodies are a subset of the antibodies produced against SARS-CoV-2, but they are considered linked to protective immunity due to their ability to block the viruses from entering the host cells.(6) Among our cohort of 75 COVID-19 patients representing in total 114 samples, we determine the neutralizing capacity 3 using a pseudovirus neutralization test (pVNT) and a surrogate virus neutralization test (sVNT), two methods we described previously. (7) Results are presented in Table 1 and Figure 1 . One hundred and four samples were positive with the Roche RBD total assay but among them, 16 (15%) were negative with the pVNT though some showing high Roche RBD total antibody titers (range from 1.13 to 2,219 AU/mL). These results are consistent with those obtained with the sVNT. Therefore, such results can provide inaccurate information on the level of protection against SARS-CoV-2 since some patients generate antibodies which are not neutralizing. However, among those who produce neutralizing antibodies, there is a correlation between the level of antibodies against RBD and their neutralizing capacity (Figure 1) Finally, we would like to stress out that scientific observations should be interpreted as they are and should not be moderated under the pretext of potentially conveying « bad » news for the public.

Vaccination against COVID-19 has proven and still prove efficacy but the decline in antibody titers should question the scientific community on the long-term protection against SARS-CoV-2 infection.

5

This research has been funded in own founds from the University of Namur.

The authors declare no conflict of interest in relation to the present study. 

Post-SARS-CoV-2 vaccination specific antibody decrease : let's get the half-full glass perspective

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Elecsys Anti-SARS-CoV-2 S Immune Response to SARS-CoV-2 Infection & Vaccination -Questions & Answers

Deconstructing the Antiviral Neutralizing-Antibody Response: Implications for Vaccine Development and Immunity

Neutralizing Antibodies in COVID-19 Patients and Vaccine Recipients after Two Doses of BNT162b2

Covid-19 Breakthrough Infections in Vaccinated Health Care Workers

Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection. Nature medicine

Performance of the rapid highthroughput automated electrochemiluminescence immunoassay targeting total antibodies to the SARS-CoV-2 spike protein receptor binding domain in comparison to the neutralization assay