CMV seropositivity in older adults changes the T cell repertoire, but does not prevent antibody or cellular responses to SARS-CoV-2 vaccination

  1. Jessica A. Breznik
  2. Angela Huynh
  3. Ali Zhang
  4. Lucas Bilaver
  5. Hina Bhakta
  6. Hannah D. Stacey
  7. Jann C. Ang
  8. Jonathan L. Bramson
  9. Ishac Nazy
  10. Matthew S. Miller
  11. Judah Denburg
  12. Andrew P. Costa
  13. Dawn M. E. Bowdish
  14. other members of the COVID-in-LTC Investigator Group

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Abstract

Chronic infection with human cytomegalovirus (CMV) may contribute to poor vaccine efficacy in older adults. We assessed effects of CMV serostatus on antibody quantity and quality, as well as cellular memory recall responses, after 2 and 3 SARS-CoV-2 mRNA vaccine doses, in older adults in assisted living facilities. CMV serostatus did not affect anti-Spike and anti-RBD IgG antibody levels, nor neutralization capacity against wildtype or beta variants of SARS-CoV-2 several months after vaccination. CMV seropositivity altered T cell expression of senescence-associated markers and increased T EMRA cell numbers, as has been previously reported; however, this did not impact Spike-specific CD4 + T cell memory recall responses. CMV seropositive individuals did not have a higher incidence of COVID-19, though prior infection influenced humoral immunity. Therefore, CMV seropositivity may alter T cell composition but does not impede the durability of humoral protection or cellular memory responses after SARS-CoV-2 mRNA vaccination in older adults.

Key Points

CMV seropositive older adults have more EMRA and terminally differentiated T cells CMV seropositivity does not prevent antibody maintenance after SARS-CoV-2 vaccination CMV seropositivity does not impede SARS-CoV-2 vaccine T cell memory recall responses

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  1. Version published to 10.1101/2022.05.27.22275673v2 on medRxiv
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    SciScore for 10.1101/2022.05.27.22275673: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: All protocols were approved by the Hamilton Integrated Research Ethics Board, and informed consent was obtained.
    Consent: All protocols were approved by the Hamilton Integrated Research Ethics Board, and informed consent was obtained.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Measurements of Anti-SARS-CoV-2 Antibodies and Neutralizing Capacity: Serum anti-SARS-CoV-2 spike (S) protein and receptor binding domain (RBD) IgG, IgA and IgM antibodies were measured by a validated ELISA as previously described47, 52, with assay cut-off 3 standard deviations above the mean of a pre-COVID-19 population from the same geographic region.
    Anti-SARS-CoV-2
    suggested: None
    anti-SARS-CoV-2 spike (S) protein and receptor binding domain (RBD) IgG
    suggested: None
    IgM
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Antibody neutralization capacity was assessed by cell culture assays with Vero E6 (ATCC CRL-1586) cells and live SARS-CoV-2, with data reported as geometric microneutralization titers at 50% (MNT50), which ranged from below detection (MNT50 = 5; 1:10 dilution) to MNT50 = 128052.
    Vero E6
    suggested: None
    Software and Algorithms
    SentencesResources
    Data was gated with FlowJo V10.8.1 (TreeStar, Inc.) as previously published47.
    FlowJo
    suggested: (FlowJo, RRID:SCR_008520)
    Negative control (unstimulated wells) and positive control (polyclonal stimulation with CytoStim™ (0.5 µL/well, #130-092-173; Miltenyi Biotec, Bergisch Gladbach, Germany) conditions were included with each sample, as was stimulation with influenza hemagglutinin (HA) antigens (4 µL; AgriFlu, Alfuria® Tetra Inactivated Influenza Vaccine 2020-2021 season, Seqirus, UK).
    CytoStim™
    suggested: None
    The beta variant was obtained through BEI Resources, NIAID, NIH: SARS-Related Coronavirus 2, Isolate hCoV-19/South Africa/KRISP-K005325/2020, NR-54009, contributed by Alex Sigal and Tulio de Oliveira. Statistical Analysis: Statistical analyses were conducted using GraphPad Prism version 9 (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: 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.

    About SciScore

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  3. Version published to 10.1101/2022.05.27.22275673v1 on medRxiv