Neutralization of Severe Acute Respiratory Syndrome Coronavirus 2 Omicron Variant by Sera From BNT162b2 or CoronaVac Vaccine Recipients

  1. Lu Lu
  2. Bobo Wing Yee Mok
  3. Lin Lei Chen
  4. Jacky Man Chun Chan
  5. Owen Tak Yin Tsang
  6. Bosco Hoi Shiu Lam
  7. Vivien Wai Man Chuang
  8. Allen Wing Ho Chu
  9. Wan Mui Chan
  10. Jonathan Daniel Ip
  11. Brian Pui Chun Chan
  12. Ruiqi Zhang
  13. Cyril Chik Yan Yip
  14. Vincent Chi Chung Cheng
  15. Kwok Hung Chan
  16. Dong Yan Jin
  17. Ivan Fan Ngai Hung
  18. Kwok Yung Yuen
  19. Honglin Chen
  20. Kelvin Kai Wang To

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Abstract

Background

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) omicron variant, designated as a variant of concern by the World Health Organization, carries numerous spike mutations that are known to evade neutralizing antibodies elicited by coronavirus disease 2019 (COVID-19) vaccines. A deeper understanding of the susceptibility of omicron variant to vaccine-induced neutralizing antibodies is urgently needed for risk assessment.

Methods

Omicron variant strains HKU691 and HKU344-R346K were isolated from patients using TMPRSS2-overexpressing VeroE6 cells. Whole genome sequence was determined using nanopore sequencing. Neutralization susceptibility of ancestral lineage A virus and the omicron, delta and beta variants to sera from 25 BNT162b2 and 25 CoronaVac vaccine recipients was determined using a live virus microneutralization assay.

Results

The omicron variant strain HKU344-R346K has an additional spike R346K mutation, which is present in 8.5% of strains deposited in the GISAID database. Only 20% and 24% of BNT162b2 recipients had detectable neutralizing antibody against the omicron variant HKU691 and HKU344-R346K, respectively, whereas none of the CoronaVac recipients had detectable neutralizing antibody titer against either omicron isolate. For BNT162b2 recipients, the geometric mean neutralization antibody titers (GMTs) of the omicron variant isolates (5.43 and 6.42) were 35.7–39.9-fold lower than that of the ancestral virus (229.4), and the GMTs of both omicron variant isolates were significantly lower than those of the beta and delta variants. There was no significant difference in the GMTs between HKU691 and HKU344-R346K.

Conclusions

Omicron variant escapes neutralizing antibodies elicited by BNT162b2 or CoronaVac. The additional R346K mutation did not affect the neutralization susceptibility. Our data suggest that the omicron variant may be associated with lower COVID-19 vaccine effectiveness.

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  1. ScreenIT

    SciScore for 10.1101/2021.12.13.21267668: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    EthicsField Sample Permit: Serum specimens from recipients of BNT162b2 or Coronavac vaccines were collected in a vaccine trial conducted at two vaccination centers in Hong Kong [12].
    IRB: This study was approved by the the Institutional Review Board of the University of Hong Kong/Hospital Authority Hong Kong West Cluster (UW 13-265; UW-21-214), and the Kowloon West Cluster REC (KW/EX-20-038[144-26]).
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Experimental Models: Cell Lines
    SentencesResources
    Duplicates of each serum was mixed with 100 TCID50 of a lineage A virus (GISAID accession number: EPI_ISL_434571), a B.1.351 (Beta variant) (GISAID accession number: EPI_ISL_2423556), B.1.617.2 (delta variant) (GISAID accession number: EPI_ISL_3221329) virus isolates for 1 hour, and the serum-virus mixture was then added to VeroE6/TMPRSS2 cells.
    VeroE6/TMPRSS2
    suggested: JCRB Cat# JCRB1819, RRID:CVCL_YQ49)
    Software and Algorithms
    SentencesResources
    Statistical analysis: Statistical analysis was performed using SPSS 26.0 (IBM SPSS Statistics) and GraphPad PRISM 9.1.1 (
    SPSS
    suggested: (SPSS, RRID:SCR_002865)
    GraphPad PRISM
    suggested: (GraphPad Prism, RRID:SCR_002798)
    GraphPad Software, San Diego CA, USA)
    GraphPad
    suggested: (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:
    There are several limitations in this study. First, we assessed serum specimens that were collected 56 days after the first dose of vaccine. Since antibody waning is well reported [27], it is likely that the neutralization antibody titer and seropositive rate would be lower for serum collected longer after the vaccination. Second, this study only included adult vaccine recipients. Since the antibody titer can be higher among adolescents and children, studies in the pediatric age group would be required. Third, we have not assessed the T cell immunity against the Omicron variant, which correlates with disease severity. Fourth, since all Coronavac recipients had an MN titer of <10 against the Omicron variant and the GMT against the ancestral virus is only 21.73, an accurate fold-reduction in neutralizing antibody titer cannot be determined. In conclusion, the reduced susceptibility of Omicron variant to vaccine-induced neutralizing antibody, together with the rapid spread of this variant, suggests that newer generation vaccines should be designed to cover this variant. However, before the availability of these next generation vaccines, booster doses of currently available vaccines will likely render most people having protective levels of neutralizing antibody titers.

    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.

    About SciScore

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  2. Version published to 10.1093/cid/ciab1041
  3. Version published to 10.1101/2021.12.13.21267668v1 on medRxiv