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Front Immunol . Persistence of spike-specific immune responses in BNT162b2-vaccinated donors and generation of rapid ex-vivo T cells expansion prot

tetano

Editor, Senior Moderator
Front Immunol


. 2023 Feb 2;14:1061255.
doi: 10.3389/fimmu.2023.1061255. eCollection 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[SUP] 1 2 [/SUP], Maysaloun Merhi[SUP] 1 2 [/SUP], Varghese P Inchakalody[SUP] 1 2 [/SUP], Nassiba Taib[SUP] 1 2 [/SUP], Maria K Smatti[SUP] 3 [/SUP], Fareed Ahmad[SUP] 4 5 [/SUP], Afsheen Raza[SUP] 1 2 [/SUP], Fatma H Ali[SUP] 3 [/SUP], Shereena Hydrose[SUP] 1 2 [/SUP], Queenie Fernandes[SUP] 1 6 [/SUP], Abdul W Ansari[SUP] 4 5 [/SUP], Fairooz Sahir[SUP] 4 [/SUP], Lobna Al-Zaidan[SUP] 1 2 [/SUP], Munir Jalis[SUP] 1 2 [/SUP], Mokhtar Ghoul[SUP] 1 2 [/SUP], Niloofar Allahverdi[SUP] 1 2 [/SUP], Mohammed U Al Homsi[SUP] 2 [/SUP], Shahab Uddin[SUP] 4 5 [/SUP], Andrew Martin Jeremijenko[SUP] 7 [/SUP], Mai Nimir[SUP] 7 [/SUP], Laith J Abu-Raddad[SUP] 8 9 10 [/SUP], Fatma Ben Abid[SUP] 7 [/SUP], Ahmed Zaqout[SUP] 7 [/SUP], Sameer R Alfheid[SUP] 7 [/SUP], Hassan Mohamed Hassan Saqr[SUP] 11 [/SUP], Ali S Omrani[SUP] 6 7 [/SUP], Ali Ait Hssain[SUP] 12 [/SUP], Muna Al Maslamani[SUP] 7 [/SUP], Hadi M Yassine[SUP] 3 [/SUP], Said Dermime[SUP] 1 2 [/SUP]



Affiliations

Abstract

Introduction: The 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.
Methods: Here, we dissect the vaccine-induced humoral and cellular responses in a cohort of six healthy recipients of two doses of this vaccine.
Results and discussion: Overall, 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.

Keywords: COVID-19 vaccine; SARS-CoV-2; spike-specific T cells expansion; spike-specific immune responses; surrogate neutralization.
 
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