Frontiers in Immunology (Feb 2023)

Persistence of spike-specific immune responses in BNT162b2-vaccinated donors and generation of rapid ex-vivo T cells expansion protocol for adoptive immunotherapy: A pilot study

  • Sarra Mestiri,
  • Sarra Mestiri,
  • Maysaloun Merhi,
  • Maysaloun Merhi,
  • Varghese P. Inchakalody,
  • Varghese P. Inchakalody,
  • Nassiba Taib,
  • Nassiba Taib,
  • Maria K. Smatti,
  • Fareed Ahmad,
  • Fareed Ahmad,
  • Afsheen Raza,
  • Afsheen Raza,
  • Fatma H. Ali,
  • Shereena Hydrose,
  • Shereena Hydrose,
  • Queenie Fernandes,
  • Queenie Fernandes,
  • Abdul W. Ansari,
  • Abdul W. Ansari,
  • Fairooz Sahir,
  • Lobna Al-Zaidan,
  • Lobna Al-Zaidan,
  • Munir Jalis,
  • Munir Jalis,
  • Mokhtar Ghoul,
  • Mokhtar Ghoul,
  • Niloofar Allahverdi,
  • Niloofar Allahverdi,
  • Mohammed U. Al Homsi,
  • Shahab Uddin,
  • Shahab Uddin,
  • Andrew Martin Jeremijenko,
  • Mai Nimir,
  • Laith J. Abu-Raddad,
  • Laith J. Abu-Raddad,
  • Laith J. Abu-Raddad,
  • Fatma Ben Abid,
  • Ahmed Zaqout,
  • Sameer R. Alfheid,
  • Hassan Mohamed Hassan Saqr,
  • Ali S. Omrani,
  • Ali S. Omrani,
  • Ali Ait Hssain,
  • Muna Al Maslamani,
  • Hadi M. Yassine,
  • Said Dermime,
  • Said Dermime

DOI
https://doi.org/10.3389/fimmu.2023.1061255
Journal volume & issue
Vol. 14

Abstract

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IntroductionThe BNT162b2 mRNA-based vaccine has shown high efficacy in preventing COVID-19 infection but there are limited data on the types and persistence of the humoral and T cell responses to such a vaccine.MethodsHere, we dissect the vaccine-induced humoral and cellular responses in a cohort of six healthy recipients of two doses of this vaccine.Results and discussionOverall, there was heterogeneity in the spike-specific humoral and cellular responses among vaccinated individuals. Interestingly, we demonstrated that anti-spike antibody levels detected by a novel simple automated assay (Jess) were strongly correlated (r=0.863, P<0.0001) with neutralizing activity; thus, providing a potential surrogate for neutralizing cell-based assays. The spike-specific T cell response was measured with a newly modified T-spot assay in which the high-homology peptide-sequences cross-reactive with other coronaviruses were removed. This response was induced in 4/6 participants after the first dose, and all six participants after the second dose, and remained detectable in 4/6 participants five months post-vaccination. We have also shown for the first time, that BNT162b2 vaccine enhanced T cell responses also against known human common viruses. In addition, we demonstrated the efficacy of a rapid ex-vivo T cell expansion protocol for spike-specific T cell expansion to be potentially used for adoptive-cell therapy in severe COVID-19, immunocompromised individuals, and other high-risk groups. There was a 9 to 13.7-fold increase in the number of expanded T cells with a significant increase of anti-spike specific response showing higher frequencies of both activation and cytotoxic markers. Interestingly, effector memory T cells were dominant in all four participants’ CD8+ expanded memory T cells; CD4+ T cells were dominated by effector memory in 2/4 participants and by central memory in the remaining two participants. Moreover, we found that high frequencies of CD4+ terminally differentiated memory T cells were associated with a greater reduction of spike-specific activated CD4+ T cells. Finally, we showed that participants who had a CD4+ central memory T cell dominance expressed a high CD69 activation marker in the CD4+ activated T cells.

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