Mucosal and systemic responses to SARS-CoV-2 vaccination in infection naïve and experienced individuals

  1. Mohammad M. Sajadi
  2. Amber Myers
  3. James Logue
  4. Saman Saadat
  5. Narjes Shokatpour
  6. James Quinn
  7. Michelle Newman
  8. Megan Deming
  9. Zahra Rikhtegaran Tehrani
  10. Maryam Karimi
  11. Abdolrahim Abbasi
  12. Mike Shlyak
  13. Matthew B. Frieman
  14. Shane Crotty
  15. Anthony D. Harris

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Abstract

With much of the world infected with or vaccinated against SARS-CoV-2, understanding the immune responses to the SARS-CoV-2 spike (S) protein in different situations is crucial to controlling the pandemic. We studied the clinical, systemic, mucosal, and cellular responses to two doses of SARS-CoV-2 mRNA vaccines in 62 individuals with and without prior SARS-CoV-2 exposure that were divided into three groups based on serostatus and/or degree of symptoms: Antibody negative, Asymptomatic, and Symptomatic. In the previously SARS-CoV-2-infected (SARS2-infected) Asymptomatic and Symptomatic groups, symptoms related to a recall response were elicited after the first vaccination. Anti-S trimer IgA and IgG levels peaked after 1 st vaccination in the SARS2-infected groups, and were higher that the in the SARS2-naive group in the plasma and nasal samples at all time points. Neutralizing antibodies titers were also higher against the WA-1 and B.1.617.2 (Delta) variants of SARS-CoV-2 in the SARS2-infected compared to SARS2-naïve vaccinees. After the first vaccination, differences in cellular immunity were not evident between groups, but the AIM + CD4 + cell response correlated with durability of humoral immunity against the SARS-CoV-2 S protein. In those SARS2-infected, the number of vaccinations needed for protection, the durability, and need for boosters are unknown. However, the lingering differences between the SARS2-infected and SARS2-naïve up to 10 months post-vaccination could explain the decreased reinfection rates in the SARS2-infected vaccinees recently reported and suggests that additional strategies (such as boosting of the SARS2-naïve vaccinees) are needed to narrow the differences observed between these groups.

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  1. ScreenIT

    SciScore for 10.1101/2021.12.13.472159: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: All volunteers in this study provided informed consent for the IRB approved study (University of Maryland, Baltimore).
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Study Design: HCW who had previously enrolled in a hospital-wide serosurvey study in the summer of 2020 (4), conducted at the University of Maryland Medical Center, were randomly contacted based on stratification into three groups, as previously described (13): SARS-CoV-2 IgG antibody negative (Ab negative); IgG positive asymptomatic and minimally symptomatic COVID-19 (Asymptomatic); and IgG positive with history of symptomatic (> 3 days of symptoms) COVID-19 (Symptomatic).
    SARS-CoV-2 IgG
    suggested: None
    Additionally, antibody responses to the secretory component (SC), indicative of secretory IgA or IgM, were evaluated in nasal and plasma samples.
    IgM
    suggested: None
    Fifteen minutes prior to the addition of the MPs, 0.5 μg/mL anti-CD40 mAb (Miltenyi Biotec) and CXCR5 antibody were added.
    anti-CD40
    suggested: None
    CXCR5
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    This admixture was added to Vero cells, and cytopathic effect was assayed visually.
    Vero
    suggested: CLS Cat# 605372/p622_VERO, RRID:CVCL_0059)
    Software and Algorithms
    SentencesResources
    T cell data was analyzed using FlowJo 10.7.1.
    FlowJo
    suggested: (FlowJo, RRID:SCR_008520)
    Statistical analysis was carried out with GraphPad Prism 5 (GraphPad Software).
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    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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  2. Version published to 10.1101/2021.12.13.472159v1 on bioRxiv