Neutralizing antibody responses to SARS-CoV-2 variants in vaccinated Ontario long-term care home residents and workers

  1. Kento T. Abe
  2. Queenie Hu
  3. Mohammad Mozafarihashjin
  4. Reuben Samson
  5. Kathy Manguiat
  6. Alyssia Robinson
  7. Bhavisha Rathod
  8. W. Rod Hardy
  9. Jenny H. Wang
  10. Mariam Iskilova
  11. Adrian Pasculescu
  12. Mahya Fazel-Zarandi
  13. Angel Li
  14. Aimee Paterson
  15. Gary Chao
  16. Karen Green
  17. Lois Gilbert
  18. Shiva Barati
  19. Nazrana Haq
  20. Alyson Takaoka
  21. Julia Garnham Takaoka
  22. Keelia Quinn De Launay
  23. Christine Fahim
  24. Salma Sheikh-Mohamed
  25. Yuko Arita
  26. Yves Durocher
  27. Eric G. Marcusson
  28. Jennifer L. Gommerman
  29. Mario Ostrowski
  30. Karen Colwill
  31. Sharon E. Straus
  32. Heidi Wood
  33. Allison J. McGeer
  34. Anne-Claude Gingras

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Abstract

Prioritizing Ontario’s long-term care home (LTCH) residents for vaccination against severe acute respiratory syndrome coronavirus 2 has drastically reduced their disease burden; however, recent LTCH outbreaks of variants of concern (VOCs) have raised questions regarding their immune responses. In 198 residents, mRNA vaccine dose 1 elicited partial spike and receptor binding domain antibody responses, while the second elicited a response at least equivalent to convalescent individuals in most residents. Residents administered mRNA-1273 (Moderna) mounted stronger total and neutralizing antibody responses than those administered BNT162b2 (Pfizer-BioNTech). Two to four weeks after dose 2, residents ( n = 119, median age 88) produced 4.8–6.3-fold fewer neutralizing antibodies than staff ( n = 78; median age 47) against wild-type (with D614G) pseudotyped lentivirus, and residents administered BNT162b2 produced 3.89-fold fewer neutralizing antibodies than those who received mRNA-1273. These effects were exacerbated upon serum challenge with pseudotyped VOC spike, with up to 7.94-fold reductions in B.1.351 (Beta) neutralization. Cumulatively, weaker vaccine stimulation, age/comorbidities, and the VOC produced an ∼130-fold reduction in apparent neutralization titers in LTCH residents and 37.9% of BNT162b2-vaccinated residents had undetectable neutralizing antibodies to B.1.351. Continued immune response surveillance and additional vaccine doses may be required in this population with known vulnerabilities.

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  1. Version published to 10.1101/2021.08.06.21261721v2 on medRxiv
  2. ScreenIT

    SciScore for 10.1101/2021.08.06.21261721: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: The study team then contacted staff and residents/substitute decision makers for consent to participate.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    BlindingAll values are calculated using automated scripts, prior to consideration of the meta-data; the investigators performing the measurements were blinded to the sample description.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    PRNT50 titers and PRNT90 titers ≥ 20 were considered positive for SARS-CoV-2 neutralizing antibodies, whereas titers <20 were considered negative.
    SARS-CoV-2 neutralizing antibodies,
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    HEK293TN and HEK293-ACE2/TMPRSS2 cells were maintained at 85% confluency for no more than 25 passages.
    HEK293TN
    suggested: RRID:CVCL_UL49)
    HEK293-ACE2/TMPRSS2
    suggested: None
    After 1 hour of incubation at 37°C and 5% CO2, 100 μL of each antibody-virus mixture was added in duplicate to 12-well plates containing Vero E6 cells at 95–100% confluence, and 100 μL of each control was added in triplicate to two sets of 12-well plates containing Vero E6 cells.
    Vero E6
    suggested: RRID:CVCL_XD71)
    Recombinant DNA
    SentencesResources
    They were co-transfected with packaging (psPAX2, Addgene, Watertown, MA, USA, #12260) and luciferase reporter constructs (pHAGE-CMV-Luc2-IRES-ZsGreen-W, kindly provided by Jesse Bloom) into HEK293TN cells (System Biosciences, Palo Alto, CA, USA, LV900A-1)
    psPAX2
    suggested: RRID:Addgene_12260)
    pHAGE-CMV-Luc2-IRES-ZsGreen-W
    suggested: RRID:Addgene_164432)
    Software and Algorithms
    SentencesResources
    Unless otherwise specified, 50% neutralization titer (ID50) values of patient sera were calculated in GraphPad Prism 9 (GraphPad Software, San Diego, CA, USA) using a nonlinear regression (log[inhibitor] versus normalized response – variable slope) algorithm.
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)
    Analysis of factors associated with humoral response to COVID-19 vaccines: Data on clinical response and antibody titers were entered into excel, cleaned and analyzed in SAS version 0.4 for PC (SAS Institute, Cary, NC).
    SAS Institute
    suggested: (Statistical Analysis System, RRID:SCR_008567)

    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 some other limitations to this study: we have only analyzed the response to COVID-19 the mRNA vaccines, with both doses administered on the schedule recommended by the vaccine manufacturers. It is noteworthy that in Ontario, LTCH residents were prioritized for vaccination with mRNA vaccines administered according to the product monograph. However, LTCH residents in some other provinces of Canada, as well as many older adults and individuals with immune system deficiencies have been vaccinated across the country with two doses of mRNA vaccines spaced further apart in order to accommodate vaccine supply issues. Another segment of the population has been vaccinated with the ChAdOx1-S vaccine (from AstraZeneca or COVISHIELD), which yields lower neutralizing antibodies [16]. Importantly, heterologous dose regimens (particularly for those who received ChAdOx1-S vaccine as a first dose) have been widely used in Canada, but their effect on the humoral response in older adults is still not known. Furthermore, we have only looked at the response 2–4 weeks after dose 2, and it will be critical to profile the decline in antibody production in this priority population. Lastly, it is possible that as the virus continues to evolve, new variants may further evade or overwhelm the blunted humoral response generated by vaccination in these older and frail adults. In conclusion, our results raise further concern that even the most effective current vaccines provide only partial protec...

    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

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  3. Version published to 10.1101/2021.08.06.21261721v1 on medRxiv