The E484K mutation in the SARS-CoV-2 spike protein reduces but does not abolish neutralizing activity of human convalescent and post-vaccination sera
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Abstract
One year in the coronavirus disease 2019 (COVID-19) pandemic, the first vaccines are being rolled out under emergency use authorizations. It is of great concern that newly emerging variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can escape antibody-mediated protection induced by previous infection or vaccination through mutations in the spike protein. The glutamate (E) to Lysine (K) substitution at position 484 (E484K) in the receptor binding domain (RBD) of the spike protein is present in the rapidly spreading variants of concern belonging to the B.1.351 and P.1 lineages. We performed in vitro microneutralization assays with both the USA-WA1/2020 virus and a recombinant (r)SARS-CoV-2 virus that is identical to USA-WA1/2020 except for the E484K mutation introduced in the spike RBD. We selected 34 sera from study participants based on their SARS-CoV-2 spike ELISA antibody titer (negative [N=4] versus weak [N=8], moderate [N=11] or strong positive [N=11]). In addition, we included sera from five individuals who received two doses of the Pfizer SARS-CoV-2 vaccine BNT162b2. Serum neutralization efficiency was lower against the E484K rSARS-CoV-2 (vaccination samples: 3.4 fold; convalescent low IgG: 2.4 fold, moderate IgG: 4.2 fold and high IgG: 2.6 fold) compared to USA-WA1/2020. For some of the convalescent donor sera with low or moderate IgG against the SARS-CoV-2 spike, the drop in neutralization efficiency resulted in neutralization ID 50 values similar to negative control samples, with low or even absence of neutralization of the E484K rSARS-CoV-2. However, human sera with high neutralization titers against the USA-WA1/2020 strain were still able to neutralize the E484K rSARS-CoV-2. Therefore, it is important to aim for the highest titers possible induced by vaccination to enhance protection against newly emerging SARS-CoV-2 variants. Two vaccine doses may be needed for induction of high antibody titers against SARS-CoV-2. Postponing the second vaccination is suggested by some public health authorities in order to provide more individuals with a primer vaccination. Our data suggests that this may leave vaccinees less protected against newly emerging variants.
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SciScore for 10.1101/2021.01.26.21250543: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: Serum samples from human subjects: The study protocols for the collection of clinical specimens from individuals with and without SARS-CoV-2 infection by the Personalized Virology Initiative were reviewed and approved by the Mount Sinai Hospital Institutional Review Board (IRB-16-00791; IRB-20-03374).
Consent: All participants provided informed consent prior to collection of specimen and clinical information.Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources After blocking, the cells were incubated with … SciScore for 10.1101/2021.01.26.21250543: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: Serum samples from human subjects: The study protocols for the collection of clinical specimens from individuals with and without SARS-CoV-2 infection by the Personalized Virology Initiative were reviewed and approved by the Mount Sinai Hospital Institutional Review Board (IRB-16-00791; IRB-20-03374).
Consent: All participants provided informed consent prior to collection of specimen and clinical information.Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources After blocking, the cells were incubated with anti-SARS-CoV-2 NP and anti-spike monoclonal antibodies, mixed in 1:1 ratio, for 1.5 hours at room temperature. anti-SARS-CoV-2 NPsuggested: Noneanti-spikesuggested: NoneThe cells were washed in 1xPBS and incubated with 1:5000 diluted HRP-conjugated anti-mouse IgG secondary antibody for 1 hour at RT followed by a brief PBS wash. anti-mouse IgGsuggested: NoneExperimental Models: Cell Lines Sentences Resources For TCID50 calculation, the virus stock was serially diluted 10-fold starting with 1:10 dilution and incubated on Vero-E6 cells for 48 hours followed by fixation in 4% Formaldehyde. Vero-E6suggested: NoneResults from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
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