Identification of a promiscuous conserved CTL epitope within the SARS-CoV-2 spike protein

The COVID-19 disease caused by infection with SARS-CoV-2 and its variants is devastating to the global public health and economy. To date, over a hundred COVID-19 vaccines are known to be under development and the few that have been approved to fight the disease are using the spike protein as the primary target antigen. Although virus neutralizing epitopes are mainly located within the RBD of the spike protein, the presence of T cell epitopes, particularly the CTL epitopes that are likely to be needed for killing infected cells, has received comparatively little attention. In this study, we predicted several potential T cell epitopes with web-based analytic tools, and narrowed them down from several potential MHC-I and MHC-II epitopes by ELIspot and cytolytic assays to a conserved MHC-I epitope. The epitope is highly conserved in current viral variants including the most recent Omicron and compatible with presentation by most HLA alleles worldwide. In conclusion, we identified a CTL epitope suitable for evaluating the CD8+ T cell-mediated cellular response and potentially for addition into future COVID-19 vaccine candidates to maximize CTL responses against SARS-CoV-2.

Comparison of Wild Type DNA Sequence of Spike Protein from SARS-CoV-2 with Optimized Sequence on The Induction of Protective Responses Against SARS-Cov-2 Challenge in Mouse Model

COVID-19 caused by SARS-CoV-2 has been spreading worldwide. To date, several vaccine candidates moved into EUA or CA applications. Although DNA vaccine is on phase III clinical trial, it is a promised technology platform with many advantages. Here, we showed that the pGX9501 DNA vaccine encoded the spike full-length protein-induced strong humoral and cellular immune responses in mice with higher neutralizing antibodies, blocking the hACE2-RBD binding against live virus infection in vitro. Importantly, higher levels of IFN-{gamma} expression in CD8+ and CD4+ T cell and specific cytotoxic lymphocyte (CTL) killings effect were also observed in the pGX9501-immunized group. It provided subsequent protection against virus challenges in the hACE2 transgenic mouse model. Overall, pGX9501 was a promising DNA vaccine candidate against COVID-19, inducing strong humoral immunity and cellular immunity that contributed to the vaccines protective effects.

Effect of Newcastle disease virus-like particles on dendritic cell maturation / 中国兽医学报

Newcastle disease virus-like particles (NDV VLPs) are composed of matrix protein (M) as the skeleton,with the insertion of hemagglutinin-neuraminidase and/or fusion protein.NDV VLPs are reported to be immunogenic and can induce specific humoral and cellular immune responses.However,its relationship with innate immunity remains elusive.Dendritic cells (DCs) are a group of specialized antigen presenting cells,which are crucial in connecting innate immunity and adaptive immunity.In this study,NDV VLPs and murine DCs were used to investigate the connection between NDV VLPs and innate immunity.The DC maturation induced by NDV VLPs (M+ HN) was evaluated.The results showed that NDV VLPs could be effectively taken up by DC and presented to naive T cells.NDV VLPs-induced DC significantly up-regulated the expression of MHC Ⅱ and costimulatory molecules on DC surface,and subsequently promoted the secretion of proinflammatory cytokines.This experiments also showed that different assembled NDV VLPs induced significant stimulating ability in cytokine levels.In summary,NDV VLPs can induce DC maturation,which gives insights to better understanding of VLPs-mediated innate immunity and provide information in selecting preferred NDV VLPs candidate.

Incremental value of 99Tcm-MIBI SPECT/CT imaging on the preoperative diagnosis of primary hyperparathyroidism / 中华核医学与分子影像杂志

Objective To investigate the incremental value of 99Tcm-MIBI SPECT/CT imaging in the preoperative diagnosis of PHPT.Methods Forty-one patients (13 males,28 females,age range:14-82 (50.0± 13.2) years)with PHPT were retrospectively enrolled.99Tcm-MIBI dual-phase planar scan,SPECT/CT imaging,CT and neck ultrasound were performed before surgery.All patients had pathological results.McNemarx2 test was used to compare the detection rates of the four imaging methods.ROI method was applied to calculate the uptake ratio (T/NT) and Pearson correlation analysis was used to evaluate correlation between T/NT and serum intact PTH,Ca,the lesion volume measured after parathyroidectomy.Results A total of 42 parathyroid lesions were confirmed by pathology.There were 39 patients with parathyroid adenoma (2 with double adenomas,and 37 with single adenoma containing 2 ectopic adenomas) and 1 patient with parathyroid carcinoma.The detection rate of planar scan,SPECT/CT imaging,CT and neck ultrasound were 78.0％ (32/41),92.7％ (38/41),73.2％ (30/41) and 70.7％ (29/41) respectively.Detection rate of SPECT/CT imaging was significantly higher than that of planar scan,CT or ultrasonography (x2 =4.17,4.90,5.82,all P＜0.01).However there were no remarkable differences between the detection rate of planar scan and that of CT or ultrasonography (x2=0.08,0.36,both P＞0.05).Detection rates of CT and ultrasonography were not significantly different either (x2 =1.90,P＞0.05).T/NT in delayed planar imaging were significantly correlated with PTH,Ca and the lesion volume measured after parathyroidectomy (r =0.56,0.54,0.56,all P＜0.01).Conclusions Compared with 99Tcm-MIBI dual-phase planar scan,CT and ultrasonography,SPECT/CT imaging could be of important clinical value for preoperative localization of PHPT because of its higher detection rate and accurate anatomical localization ability.

Operational efficiency of county public general hospitals in Fujian province from 2009 to 2014 / 中国卫生政策研究

Objective:In order to provide policy-makers with basis and reference for improving the operational efficiency of county general public hospitals, this paper studies the changes in overall efficiency, technical efficiency and scale efficiency of 40 county general public hospitals in Fujian province from 2009 to 2014 , as well as how the to-tal factor productivity changes over the time. Methods: After collecting the relevant data of hospital operations from 2009 to 2014, this paper uses CCR, BBC, Malmquist model and other data envelopment analysis (DEA) methods to analyze the data. Results:The vast majority of those 40 county general public hospitals are in decreasing state. The total factor productivity of 40 hospitals from 2009 to 2014 is 1. 019. There are 21 hospitals (52. 5%) that slightly im-proved their productivity, of which 3 hospitals increased their productivity mainly due to technological progress, 3 hospitals due to efficiency increase, and the rest 15 hospitals due to the effect of both technological progress and effi-ciency increase. Conclusions:The operational efficiency of county general public hospitals in Fujian province is gen-erally insufficient, and there are significant differences between operating efficiency of different regions. The efficien-cy of hospitals in mountainous areas had increased, but the efficiency of hospitals in coastal areas had decreased. Therefore, in order to increase investment in county general public hospitals, the government should take differential policy and pay attention to the reasonable control of hospital size, as well as to strengthen the connotation building and attach importance to improving medical service technologies.