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
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التاريخ
2023-02-02المؤلف
Mestiri, SarraMerhi, Maysaloun
Inchakalody, Varghese P.
Taib, Nassiba
Smatti, Maria K.
Ahmad, Fareed
Raza, Afsheen
Ali, Fatma H.
Hydrose, Shereena
Fernandes, Queenie
Ansari, Abdul W.
Sahir, Fairooz
Al-Zaidan, Lobna
Jalis, Munir
Ghoul, Mokhtar
Allahverdi, Niloofar
Al Homsi, Mohammed U.
Uddin, Shahab
Jeremijenko, Andrew Martin
Nimir, Mai
Abu-Raddad, Laith J.
Abid, Fatma Ben
Zaqout, Ahmed
Alfheid, Sameer R.
Saqr, Hassan Mohamed Hassan
Omrani, Ali S.
Hssain, Ali Ait
Al Maslamani, Muna
Yassine, Hadi M.
Dermime, Said
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البيانات الوصفية
عرض كامل للتسجيلةالملخص
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.
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