SARS-CoV-2 BA.1 variant is neutralized by vaccine booster–elicited serum but evades most convalescent serum and therapeutic antibodies
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Abstract
The rapid spread of the highly contagious Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) along with its high number of mutations in the spike gene has raised alarms about the effectiveness of current medical countermeasures. To address this concern, we measured the neutralization of the Omicron BA.1 variant pseudovirus by postvaccination serum samples after two and three immunizations with the Pfizer/BioNTech162b2 SARS-CoV-2 mRNA (Pfizer/BNT162b2) vaccine, convalescent serum samples from unvaccinated individuals infected by different variants, and clinical-stage therapeutic antibodies. We found that titers against the Omicron variant were low or undetectable after two immunizations and in many convalescent serum samples, regardless of the infecting variant. A booster vaccination increased titers more than 30-fold against Omicron to values comparable to those seen against the D614G variant after two immunizations. Neither age nor sex was associated with the differences in postvaccination antibody responses. We also evaluated 18 clinical-stage therapeutic antibody products and an antibody mimetic protein product obtained directly from the manufacturers. Five monoclonal antibodies, the antibody mimetic protein, three antibody cocktails, and two polyclonal antibody preparations retained measurable neutralization activity against Omicron with a varying degree of potency. Of these, only three retained potencies comparable to the D614G variant. Two therapeutic antibody cocktails in the tested panel that are authorized for emergency use in the United States did not neutralize Omicron. These findings underscore the potential benefit of mRNA vaccine boosters for protection against Omicron and the need for rapid development of antibody therapeutics that maintain potency against emerging variants.
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SciScore for 10.1101/2021.12.22.473880: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: Ethics: The PASS (IDCRP-126) and EPICC (IDCRP-085) studies were approved by the Uniformed Services University of the Health Sciences Institutional Review Board (IRB) in compliance with all applicable Federal regulations governing the protection of human participants.
Consent: All PASS and EPICC study participants provided informed consent.Sex as a biological variable not detected. Randomization not detected. Blinding The antibody identities are blinded for publications per an agreement with the companies. Power Analysis not detected. Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources Neutralization assays were performed on 293T-ACE2/TMPRSS2 … SciScore for 10.1101/2021.12.22.473880: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: Ethics: The PASS (IDCRP-126) and EPICC (IDCRP-085) studies were approved by the Uniformed Services University of the Health Sciences Institutional Review Board (IRB) in compliance with all applicable Federal regulations governing the protection of human participants.
Consent: All PASS and EPICC study participants provided informed consent.Sex as a biological variable not detected. Randomization not detected. Blinding The antibody identities are blinded for publications per an agreement with the companies. Power Analysis not detected. Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources Neutralization assays were performed on 293T-ACE2/TMPRSS2 cells stably expressing ACE2 and transmembrane serine protease 2 (BEI # NR-55293) 293T-ACE2/TMPRSS2suggested: NoneSoftware and Algorithms Sentences Resources Vaccinated participants: Details of the PASS study protocol, including the inclusion/exclusion criteria, have been published(17). PASSsuggested: (PASS, RRID:SCR_005490)Neutralization curves were normalized to virus only controls and fitted using nonlinear regression curve (GraphPad Prism, La Jolla, CA). GraphPadsuggested: (GraphPad Prism, RRID:SCR_002798)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:The limitations of our study include the relatively small numbers of study subjects, restricted timing of sera collection, and the use of a pseudovirus platform as a surrogate to authentic SARS-CoV-2 viruses. Ultimately neutralization titers need to be tied to clinical outcomes. The rapid and unpredictable evolution of SARS-CoV-2 requires continued development and assessments of medical countermeasures.
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.
Results from scite Reference Check: We found no unreliable references.
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