T-cell and antibody immunity after COVID-19 mRNA vaccines in healthy and immunocompromised subjects-An exploratory study

  1. Rakesh Sindhi
  2. Chethan Ashokkumar
  3. Brianna Spishock
  4. Maggie Saunders
  5. Angelo Mabasa
  6. Pradeep Sethi
  7. Ashok Reddy
  8. Bobby Nibhanupudy

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Abstract

Background

In recent studies, up to half of immunocompromised (IC) subject populations fail to develop antibodies after COVID-19 vaccination.

Purpose and Methods

Here, we explore whether T-cells which respond to the spike (S) antigenic sequence and its less conserved S1, and the conserved S2 component are present in serial samples before and after each dose of mRNA1273 or BNT162b2 vaccines in 20 healthy immunocompetent subjects. Single samples from 7 vaccinated IC subjects were also tested. Simultaneously, we measured IgG antibodies to the receptor binding domain (RBD) of S1, and anti-S IgG, and frequencies of monocytic CD14+HLA-DR-(M-MDSC) and polymorphonuclear CD14-CD15+CD11b+ (PMN-MDSC) myeloid-derived suppressor cells.

Results

In healthy subjects, S1-, S2-, and S-reactive CD4 and CD8 T-cell frequencies showed a numeric but not statistically significant decrease after the first vaccine dose and were accompanied by increased MDSC frequencies (p<0.05). After the second dose, S2-and S-reactive CD4 and CD8 cells and MDSC approached pre-vaccination levels. In healthy subjects, a) S1-reactive CD8 frequencies were significantly higher after the second dose compared with pre-vaccination levels (p=0.015), b) anti-RBD and anti-S IgG were present in all after the second dose. Among seven IC subjects, anti-RBD and anti-S IgG were absent in 4 and 3 subjects, respectively. S1-reactive CD8 cells were identified in 2 of 4 anti-RBD negative subjects. S-reactive CD4 or CD8 cells were identified in all three anti-S negative subjects.

Conclusions

In healthy immunocompetent subjects, mRNA vaccines induce antibodies to the spike antigenic sequences and augment CD8 cells reactive to the S1 spike sequence, which is more specific for the SARS-CoV-2 virus. In this exploratory cohort of vaccinated immunocompromised subjects, S1-reactive CD8 cells can be detected in some who are negative for RBD antibody, and S-reactive T-cells are present in all who are negative for spike antibody.

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  1. ScreenIT

    SciScore for 10.1101/2021.05.21.21257442: (What is this?)

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

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Statistical analysis and correlations were performed using SPSS.
    SPSS
    suggested: (SPSS, RRID:SCR_002865)
    Dot plots were generated with GraphPad prism 9.
    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:
    The limitations of our exploratory study include the small numbers of immunocompromised vaccinated patients with different underlying conditions, our use of a single marker, CD154, in lieu of IFNγ as the marker of viral-antigen-specific cytotoxic T-cells, lack of longer-term serial immunity data from immunocompetent subjects, and single measurements from IC patients. However, our exploratory study shows that vaccination enhances T-cell immunity to SARS-CoV-2 in the form of S1-reactive CD154+CD8 T-cells in healthy immunocompetent subjects. Among IC subjects who failed to develop antibodies after vaccination, the presence of these S1-reactive CD8 cells is encouraging and warrants longitudinal confirmation in larger numbers of immunocompromised patients. Also worthy of additional study are S2- and S-reactive CD4 and CD8 cells, in vaccinated IC subjects, who do not develop anti-spike antibody. These studies can determine whether vaccination also augments pre-existing cellular immunity.

    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 10.1101/2021.05.21.21257442v1 on medRxiv