ABSTRACT
While SARS-CoV-2-specific T cells have been characterized to play essential roles in host immune protection in COVID-19 patients, few researches focus on the functional validation of T cell epitopes and development of vaccines inducing specific T cell responses. In this study, 120 CD8+ T cell epitopes from E, M, N, S and RdRp proteins were validated. Among them, 110 epitopes have not been reported previously; 110, 15, 6, 14 and 12 epitopes were highly homologous with SARS-CoV, OC43, NL63, HKU1, and 229E, respectively; 4 epitopes from S protein displayed one amino acid distinct from the current variants of SARS-CoV-2. Thirty-one epitopes restricted by HLA-A2 molecule were used to generate peptide cocktail vaccines in combination with Poly(I:C), R848 or polylactic-co-glycolic acid nanoparticles, which elicited robust specific CD8+ T cell responses in wild-type and HLA-A2/DR1 transgenic mice. Seven of the 31 epitopes were found to be cross-presented by HLA-A2 and H-2K/Db molecules. Unlike previous researches, this study established a modified cell co-culture system of DC-peptide-PBL using healthy donors PBMCs to validate the CD8+ T cell epitope on-silicon predicted; provided a library of CD8+ T cell epitopes restricted by a series of high-frequency HLA-A allotypes which covering broad Asian populations; identified the HLA-A cross-restrictions of these CD8+ T cell epitopes using competitive binding experiments with HMy2.CIR cell lines expressing indicated HLA-A molecules; and initially confirmed the in vivo feasibility of 9 or 10-mer peptide cocktail vaccines of SARS-CoV2. These data will facilitate the development of vaccines inducing antiviral CD8+ T cell responses.
ABSTRACT
OBJECTIVE To find the differences in QOL between patients treated with total laryngectomy with voice rehabilitation or without voice rehabilitation and subtotal laryngectomy, to analysis the factors affecting QOL of patients after laryngectomy by HNQOL. METHODS With HNQOL,a survey was conducted in patients treated with total laryngectomy (30cases) with voice rehabilitation, 30 cases without voice rehabilitation, and 30 cases treated with subtotal laryngectomy for laryngeal cancer. We discuss changes of QOL with time went by,and analysis the factors affecting QOL of patients after laryngectomy. RESULTS There is no difference between patients treated with total laryngectomy with .voice rehabilitation and the one treated with subtotal laryngectomy in their quality of life, however, there is difference between patients treated with total laryngectomy without voice rehabilitation and the one treated with subtotal laryngectomy. CONCLUSION Through voice rehabilitation ,we could advance quality of life of the patients treated with total laryngectomy. Through the integration of psychological, clinical and social intervention, the quality of life of patients may have an overall improvement.
