التفاصيل البيبلوغرافية
| العنوان: |
A multi-epitope/CXCL11 prime/pull coronavirus mucosal vaccine boosts the frequency and the function of lung-resident memory CD4+ and CD8+ T cells and enhanced protection against COVID-19-like symptoms and death caused by SARS-CoV-2 infection |
| المؤلفون: |
Latifa Zayou1,2, Prakash, Swayam1, Dhanushkodi, Nisha Rajeswari1, Quadiri, Afshana1, Ibraim, Izabela Coimbra3, Singer, Mahmoud1, Salem, Amirah1, Shaik, Amin Mohammed1, Suzer, Berfin1, Chilukuri, Amruth1, Tran, Jennifer1, Nguyen, Pauline Chau1, Miyo Sun1, Hormi-Carver, Kathy K.1, Belmouden, Ahmed2, Vahed, Hawa4, Gil, Daniel4, Ulmer, Jeffrey B.4, BenMohamed, Lbachir1,4,5,6 Lbenmoha@uci.edu |
| المصدر: |
Journal of Virology. Dec2023, Vol. 97 Issue 12, p1-17. 17p. |
| مصطلحات موضوعية: |
*T cells, *COVID-19 vaccines, *COVID-19 pandemic, *CHEMOKINE receptors, *COVID-19, *INTRANASAL administration, *CD8 antigen |
| مستخلص: |
The pandemic of the coronavirus disease 2019 (COVID-19) has created the largest global health crisis in almost a century. Low frequencies of functional SARSCoV-2-specific CD4+ and CD8+ T cells in the lungs of COVID-19 patients have been associated with severe cases of COVID-19. Low levels of T cell-attracting CXCL9, CXCL10, and CXCL11 chemokines in infected lungs may not be sufficient for the migration of CD4+ and CD8+ T cells from circulation into infected lungs. We hypothesize that a coronavirus vaccine strategy that boosts the frequencies of functional SARS-CoV-2-specific CD4+ and CD8+ T cells in the lungs would lead to better protection from COVID-19-like symptoms. In the present study, we designed and pre-clinically tested the safety, immunogenicity, and protective efficacy of a novel multi-epitope/CXCL11 prime/pull mucosal coronavirus vaccine. This prime/pull vaccine strategy consists of intranasal delivery of a lung-tropic adeno-associated virus type 9 vector that incorporates highly conserved human CD4+ and CD8+ cell epitopes of SARS-CoV-2 (prime) followed by recruitment of the primed T cells into the lungs using the T cell-attracting chemokine, CXCL-11 (pull). We demonstrated that the immunization of HLA-DR*0101/HLA-A*0201/hACE2 triple transgenic mice with this multi-epitope/CXCL11 prime/pull coronavirus mucosal vaccine: (i) increased the frequencies of functional CD4+ and CD8+ TEM, TCM, and TRM cells in the lungs and (ii) reduced COVID-19-like symptoms, lowered virus replication, and prevented deaths following challenge with SARS-CoV-2. These findings demonstrate that bolstering the number of functional lung-resident memory CD4+ and CD8+ T cells improved protection against SARS-CoV-2 infection, COVID-19-like symptoms, and death. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
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