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

Frontiers in Immunology

Immunology

Ali S. Omrani¹  Ahmed Zaqout²  Andrew Martin Jeremijenko²  Mai Nimir²  Muna Al Maslamani²  Sameer R. Alfheid²  Fatma Ben Abid²  Laith J. Abu-Raddad³  Ali Ait Hssain⁴  Mohammed U. Al Homsi⁵  Hadi M. Yassine⁶  Fatma H. Ali⁶  Maria K. Smatti⁶  Hassan Mohamed Hassan Saqr⁷  Queenie Fernandes⁸  Lobna Al-Zaidan⁹  Maysaloun Merhi⁹  Niloofar Allahverdi⁹  Sarra Mestiri⁹  Said Dermime⁹  Mokhtar Ghoul⁹  Nassiba Taib⁹  Varghese P. Inchakalody⁹  Shereena Hydrose⁹  Munir Jalis⁹  Afsheen Raza⁹  Fairooz Sahir^1,10  Fareed Ahmad^1,11  Abdul W. Ansari^1,11  Shahab Uddin^1,11 

[1] College of Medicine, Qatar University, Doha, Qatar;Communicable Disease Center, Hamad Medical Corporation, Doha, Qatar;Communicable Disease Center, Hamad Medical Corporation, Doha, Qatar;Infectious Disease Epidemiology Group, Weill Cornell Medicine–Qatar, Cornell University, Qatar Foundation–Education City, Doha, Qatar;World Health Organization Collaborating Centre for Disease Epidemiology Analytics on HIV/AIDS, Sexually Transmitted Infections, and Viral Hepatitis, Weill Cornell Medicine–Qatar, Cornell University, Qatar Foundation–Education City, Doha, Qatar;Department of Population Health Sciences, Weill Cornell Medicine, Cornell University, New York, NY, United States;Medical Intensive Care Unit, Hamad Medical Corporation, Doha, Qatar;National Center for Cancer Care and Research, Hamad Medical Corporation, Doha, Qatar;Qatar University Biomedical Research Center, Qatar University, Doha, Qatar;Staff Medical Center, Department of Medicine, Hamad Medical Corporation, Doha, Qatar;Translational Cancer Research Facility, National Center for Cancer Care and Research/ Translational Research Institute, Hamad Medical Corporation, Doha, Qatar;College of Medicine, Qatar University, Doha, Qatar;Translational Cancer Research Facility, National Center for Cancer Care and Research/ Translational Research Institute, Hamad Medical Corporation, Doha, Qatar;National Center for Cancer Care and Research, Hamad Medical Corporation, Doha, Qatar;Translational Research Institute, Academic Health System, Hamad Medical Corporation, Doha, Qatar;Translational Research Institute, Academic Health System, Hamad Medical Corporation, Doha, Qatar;Dermatology Institute, Academic Health System, Hamad Medical Corporation, Doha, Qatar;

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

DOI  :  10.3389/fimmu.2023.1061255

 received in 2022-10-04, accepted in 2023-01-11,  发布年份 2023

来源: Frontiers

【 摘 要 】

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.

【 授权许可】

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Copyright © 2023 Mestiri, Merhi, Inchakalody, Taib, Smatti, Ahmad, Raza, Ali, Hydrose, Fernandes, Ansari, Sahir, Al-Zaidan, Jalis, Ghoul, Allahverdi, Al Homsi, Uddin, Jeremijenko, Nimir, Abu-Raddad, Abid, Zaqout, Alfheid, Saqr, Omrani, Hssain, Al Maslamani, Yassine and Dermime