Differential neutralization and inhibition of SARS-CoV-2 variants by antibodies elicited by COVID-19 mRNA vaccines
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Abstract
The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in the emergence of new variant lineages that have exacerbated the COVID-19 pandemic. Some of those variants were designated as variants of concern/interest (VOC/VOI) by national or international authorities based on many factors including their potential impact on vaccine-mediated protection from disease. To ascertain and rank the risk of VOCs and VOIs, we analyze the ability of 14 variants (614G, Alpha, Beta, Gamma, Delta, Epsilon, Zeta, Eta, Theta, Iota, Kappa, Lambda, Mu, and Omicron) to escape from mRNA vaccine-induced antibodies. The variants show differential reductions in neutralization and replication by post-vaccination sera. Although the Omicron variant (BA.1, BA.1.1, and BA.2) shows the most escape from neutralization, sera collected after a third dose of vaccine (booster sera) retain moderate neutralizing activity against that variant. Therefore, vaccination remains an effective strategy during the COVID-19 pandemic.
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SciScore for 10.1101/2021.11.24.469906: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics Consent: This activity was approved by each participating institution, either as a research project with written informed consent or as a public health surveillance project without written informed consent.
IACUC: All personnel working with the virus were trained with relevant safety and procedure-specific protocols and their competency for performing the work in the BSL-3E laboratories was certified Recombinant DNA work was approved by CDC’s Institutional Biosafety Committee (IBC).
Field Sample Permit: The safeguard and mitigation strategies are: 1) the backbone of the reporter virus are based on the Wuhan-Hu-1 strain, which is expected to be the least transmissible strain compared to later …SciScore for 10.1101/2021.11.24.469906: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics Consent: This activity was approved by each participating institution, either as a research project with written informed consent or as a public health surveillance project without written informed consent.
IACUC: All personnel working with the virus were trained with relevant safety and procedure-specific protocols and their competency for performing the work in the BSL-3E laboratories was certified Recombinant DNA work was approved by CDC’s Institutional Biosafety Committee (IBC).
Field Sample Permit: The safeguard and mitigation strategies are: 1) the backbone of the reporter virus are based on the Wuhan-Hu-1 strain, which is expected to be the least transmissible strain compared to later variants; 2) a mNeonGreen reporter gene replaces the ORF7a in the reporter virus, which may attenuate the virus as the ORF7a protein has been reported to be an interferon antagonist21,22; 3) mutations engineered into a reporter virus are either part of or all of the spike mutations found in a natural isolate and the engineering of unnatural mutations is prohibited; 4) the reporter viruses are only to be used in in vitro studies, such as neutralization assays, and not in in vivo studies; 5) all the in vitro work is conducted in BSL-3E facilities including enhanced practices such as shower out after experiments to minimize the possibility of accidental release of the reporter virus to the environment; 6) all staff working with the reporter viruses are fully vaccinated; 7) all staff are approved for working with BSL-3E select agents with senior staff having decades of BSL-3E experience working with highly pathogenic viruses.Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Cell Line Authentication Contamination: All cells and virus stocks tested negative for mycoplasma using MycoAlert Plus reagents (Lonza) Table 2: Resources
Experimental Models: Cell Lines Sentences Resources Nucleocapsid protein expressing cell line: Vero E6 cells (ATCC, CRL-1586) were transfected using Lipofectamine 3000 (Invitrogen) with a plasmid encoding SARS-CoV-2 nucleocapsid protein via CMV3 promoter as well as mCherry2 via an IRES element. Vero E6suggested: NoneVirus rescue: To rescue the SARS-CoV-2 reporter virus, VeroE6-N cells were trypsinized, washed with Opti-MEM (ThermoFisher) and resuspended in 100 µL nucleofector solution at a concentration of 1.5 × 106 cells/100 µl following the instructions of the Nucleofector Kit V (Lonza). VeroE6-Nsuggested: NoneP1 was propagated in T-150 flasks of VeroE6/TMPRSS2 cells at a multiplicity of infection (MOI) of 0.02-0.1 for 24 hours to make the P2 working stock. VeroE6/TMPRSS2suggested: JCRB Cat# JCRB1819, RRID:CVCL_YQ49)Vero/TMPRSS2 cells growing in 96-well imaging plates were then inoculated in triplicate with 40 µL of serum-virus mixtures and incubated for 1 hour at 37°C with periodic shaking of the plates. Vero/TMPRSS2suggested: JCRB Cat# JCRB1818, RRID:CVCL_YQ48)Virus replication in Calu-3 cells: Calu-3 cells (Human lung epithelial cell line) were obtained from CDC’s Division of Scientific Resources (DSR). Calu-3suggested: BCRJ Cat# 0264, RRID:CVCL_0609)Software and Algorithms Sentences Resources Sequence confirmation: All the SARS-CoV-2 reporter viruses were sequenced by NGS to confirm the sequence of the spike gene. NGSsuggested: (PM4NGS, RRID:SCR_019164)Libraries were normalized to equimolar concentrations, pooled, and sequenced on Illumina NovaSeq 6000 (Illumina, San Diego, CA, USA) using the NovaSeq v1.5 SP Reagent Kit (300 cycles). NovaSeqsuggested: NoneThe monolayers were imaged using a BioTek Cytation3 instrument and virus foci (approximately 100-200/well in no-serum control wells) were counted using Gen5 software. Gen5suggested: (Gen5, RRID:SCR_017317)The foci counts were normalized to no-serum controls, and 4 parameter nonlinear regression analysis with bottom constraint set to 0, and top value set to 1 (GraphPad Prism v7.04) was used to fit a curve to the data and to determine the FRNT50 value. GraphPadsuggested: (GraphPad Prism, RRID:SCR_002798)Pooled Moderna or Pfizer sera was diluted to 2X or 5X concentration (FRNT50=2 or 5 against 614D reference virus) in infection media (DMEM supplemented with 2% HI-FBS and 1x pen/strep). Pfizersuggested: (Pfizer Inc., RRID:SCR_021375)Results from OddPub: Thank you for sharing your code.
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.
Results from scite Reference Check: We found no unreliable references.
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