Neutralizing antibodies to SARS‐CoV‐2 Omicron variant after third mRNA vaccination in health care workers and elderly subjects
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Abstract
The emergence of SARS‐CoV‐2 Omicron variant (B.1.1.529) with major spike protein mutations has raised concern over potential neutralization escape and breakthrough infections among vaccinated and previously SARS‐CoV‐2‐infected subjects. We measured cross‐protective antibodies against variants in health care workers (HCW, n = 20) and nursing home residents (n = 9) from samples collected at 1–2 months, following the booster (3rd) dose. We also assessed the antibody responses in subjects infected before the Omicron era (n = 38) with subsequent administration of a single mRNA vaccine dose. Following booster vaccination, HCWs had high IgG antibody concentrations to the spike protein and neutralizing antibodies (NAb) were detectable against all variants. IgG concentrations among the elderly remained lower, and some lacked NAbs against the Beta and Omicron variants. NAb titers were significantly reduced against Delta, Beta, and Omicron compared to WT virus regardless of age. Vaccination induced high IgG concentrations and variable titers of cross‐reactive NAbs in previously infected subjects, whereas NAb titers against Omicron were barely detectable 1 month postinfection. High IgG concentrations with cross‐protective neutralizing activity were detected after three Coronavirus Disease 2019 (COVID‐19) vaccine doses in HCWs. However, lower NAb titers seen in the frail elderly suggest inadequate protection against Omicron breakthrough infections, yet protection against severe COVID‐19 is expected.
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SciScore for 10.1101/2021.12.22.21268273: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics not detected. Sex as a biological variable We invited HCWs (n=20, median age 50.2 [27.2-63.1], 100% female) and elderly in residential care home (n=9, 84.2 [71.5-89.6], 44% female) to participate and donate a blood sample for measurement of SARS-CoV-2 specific serum antibodies (Supplemental Table S1). Randomization not detected. Blinding not detected. Power Analysis not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources Briefly, sera from donors were incubated with microspheres covered with SARS-CoV-2 receptor binding domain and full-length spike glycoprotein, and bound antibodies were detected with R-Phycoerythrin (RPE)-conjugated secondary antibody. R-Phyco…SciScore for 10.1101/2021.12.22.21268273: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics not detected. Sex as a biological variable We invited HCWs (n=20, median age 50.2 [27.2-63.1], 100% female) and elderly in residential care home (n=9, 84.2 [71.5-89.6], 44% female) to participate and donate a blood sample for measurement of SARS-CoV-2 specific serum antibodies (Supplemental Table S1). Randomization not detected. Blinding not detected. Power Analysis not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources Briefly, sera from donors were incubated with microspheres covered with SARS-CoV-2 receptor binding domain and full-length spike glycoprotein, and bound antibodies were detected with R-Phycoerythrin (RPE)-conjugated secondary antibody. R-Phycoerythrinsuggested: NoneExperimental Models: Cell Lines Sentences Resources All variant viruses were isolated and propagated in VeroE6-TMPRSS2-H10 cells (42) and further propagated in Vero E6 cells for MNT. VeroE6-TMPRSS2-H10suggested: NoneVero E6suggested: RRID:CVCL_XD71)Software and Algorithms Sentences Resources Statistical analyses were performed using SPSS v27 and R (v4.0.4) with Rstudio (v1.4.1106). SPSSsuggested: (SPSS, RRID:SCR_002865)Rstudiosuggested: (RStudio, RRID:SCR_000432)Results 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: We detected the following sentences addressing limitations in the study:We acknowledge several limitations in our study due to the small number of subjects and HCW gender distribution. Also, in HCW and elderly subjects, we analyzed sera after the 3rd dose, but we did not have pre-booster samples available for comparison. However, pre-booster samples likely had very low NAb titers as low Nab activity against Omicron has been reported following the second dose (19, 20, 26); and especially as 6 to 9 months had passed before the 3rd dose was administered. In this study we only assessed humoral immune responses that are critical immune mechanisms reducing infection. SARS-CoV-2 infection and vaccination also induce durable T-cell immunity, which targets multiple epitopes in the SARS-CoV-2 spike protein and is likely to enhance protection against severe COVID-19 disease against SARS-CoV-2 variants (39). Analysis of the mutations in the spike protein sequence of the Omicron variant with computational modelling suggested that the T cell response against Omicron would remain broadly cross-protective, as only a small number of the CD4+ and CD8+ T cell epitopes, and none of the immunodominant epitopes, are affected by the Omicron specific mutations (40). In summary, the results of our study support previous findings indicating that COVID-19 booster vaccinations raise IgG concentrations, although NAb titers remain low against Omicron compared to WT and Delta variants. In this study we were able to demonstrate measurable NAbs against Delta, Beta and Omicron VO...
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.
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- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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