1.Assessment and preliminary clinical application of a domestic nucleic acid detection reagent for hepatitis D virus
Yongcong LI ; Rongchen YUAN ; Kuanhui XIANG ; Guomin OU ; Tianxun HUANG ; Fangming CHENG ; Zhenchao TIAN ; Xiongwei LIU ; Xiaozhong WANG ; Feng GUO ; Yahong MA ; Jing ZHOU ; Erhei DAI ; Bangning CHENG ; Tong LI ; Tao SHEN ; Chungen QIAN
Chinese Journal of Laboratory Medicine 2024;47(3):239-244
Objective:This study aims to evaluate the quality and explore the preliminary clinical applications of a domestically developed hepatitis D virus nucleic acid quantification reagent (abbreviated as"domestic HDV RNA reagent").Methods:The sensitivity and accuracy of the reagent were evaluated in accordance with the WHO HDV RNA international standard, employing the Bio-Rad CFX Opus 96 real-time fluorescence quantitative PCR analysis system. Serial dilutions of pseudo-viruses or cell culture-derived virus were used to determine the linear range of the domestic HDV RNA reagent. Specificity was assessed using positive samples of HAV, HBV, HCV infection, and HEV national reference materials. Precision was evaluated with samples at both high and low concentrations. In a comparative analysis, 30 HDV IgG positive samples were tested using both the domestic HDV RNA reagent and the RoboGene HDV RNA kit based on the ABI 7500 FAST DX system. The Pearson correlation coefficient (r) was used to examine the correlation between the two reagents.Results:The domestic HDV RNA reagent demonstrated a high sensitivity of up to 6 IU/ml, consistent with that of the comparator reagent. The calibration curve for WHO HDV RNA standards had a slope of -3.286, with an amplification efficiency of 101.6%. The linear detection range spanned from 10 to 10 8 IU/ml for eight HDV genotypes. The domestic HDV RNA reagent exhibited exceptional specificity, without cross-reactivity observed with HAV, HBV, HCV, or HEV. Accuracy assessments at five concentration levels met the required standards, with intra-assay precision coefficient of variation ( CV) ranging from 1.20% to 4.20%, and inter-assay precision CV from 1.20% to 7.90%. The detection results for HDV IgG positive samples were highly correlated with the comparator reagent ( r=0.984, P<0.001), achieving a diagnostic accuracy of 100% compared to sequencing results. Conclusion:In this study, the domestic HDV RNA reagent possesses excellent specificity, accuracy, precision, and a broad linear range, attaining a sensitivity level on par with international reagents of the same type.
2.Glycyrrhizic Acid Showed Therapeutic Effects on Severe Pulmonary Damages in Mice Induced by Pneumonia Virus of Mice Infection
Yun LIU ; Tingting FENG ; Wei TONG ; Zhi GUO ; Xia LI ; Qi KONG ; Zhiguang XIANG
Laboratory Animal and Comparative Medicine 2024;44(3):251-258
Objective In this study,inbred BALB/c mice infected with the pneumonia virus of mice(PVM)were used to establish an animal model of viral pneumonia,and the changes in the pro-inflammatory alarmin molecule,high mobility group box 1 protein(HMGB1),during PVM infection were observed,as well as the in vivo intervention effects of the HMGB1 inhibitor,glycyrrhizic acid(GA),on PVM-induced lung injury.Methods Three-week-old female BALB/c mice were randomly divided into three groups,each consisting of 6 mice.One group,uninfected by PVM,served as the control group(Control).The other two groups were inoculated intranasally with PVM at a dose of 1×104 50%tissue culture infective dose(TCID50)/25 μL,and subsequently treated with GA saline solution(GA group)or plain saline solution(normal saline,NS group)via gavage for 15 consecutive days.During this period,changes in body weight and appearance were monitored in each group.At the end of the experiment,lung tissue samples were collected from all groups.The distribution of PVM and HMGB1 proteins in the lung tissues was analyzed using hematoxylin-eosin staining and immunohistochemistry.The expression levels of HMGB1 and its Toll-like receptor 4(TLR-4),advanced glycosylation end-product-specific receptor(AGER),and inflammatory cytokines such as interleukin(IL)-1β,IL-2,and tumor necrosis factor-α(TNF-α)in lung tissues of mice were measured using real time fluorescence quantitative PCR.Results Compared with the Control group,the NS group showed a significant weight loss after 6 days(P<0.05).Histopathological tests revealed pronounced inflammatory lesions in their lungs.Immunohistochemistry results showed that HMGB1 was released from the nucleus to the cytoplasm,and real time fluorescence quantitative PCR results indicated that the expression levels of HMGB1,IL-1β,and IL-2 were significantly upregulated(P<0.05).In the GA group,there was no significant change in the clinical symptoms or body weight.However,compared with the NS group,the pathological damages of lung tissues in the GA group were significantly reduced,and the expression levels of HMGB1,IL-1 β,IL-2,and interferon-γ(IFN-γ)in lung tissues were also significantly decreased(P<0.05),although the expression level of AGER was significantly increased(P<0.05).Conclusion PVM infection can cause significant inflammatory pathological lung damages in mice,and GA can effectively alleviate the damages.Its therapeutic effect may be related to the activation of HMGB1 signaling pathway.
3.Epidemiological characteristics and spatiotemporal clustering analysis on foodborne infection of Vibrio parahaemolyticus in Ningbo, 2014-2022
Danjie JIANG ; Yang YANG ; Yan ZHANG ; Yanbo GUO ; Jinghui WANG ; Hua GAO ; Qinghai GONG ; Jia HONG ; Feng TONG
Chinese Journal of Epidemiology 2024;45(9):1204-1208
Objective:To explore the epidemiological characteristics and spatiotemporal clustering of foodborne infection of Vibrio ( V.) parahaemolyticus in Ningbo, Zhejiang Province, from 2014 to 2022, and provide reference and evidence for the prevention and control of related diseases. Methods:The incidence data on of foodborne infection of V. parahaemolyticus in Ningbo from 2014 to 2022 were collected from Ningbo Foodborne Disease Surveillance System, and the case counts and the positive rates in different districts (counties, cities) were calculated. Spatial autocorrelation analysis and spatiotemporal scanning analysis were conducted to analyze the spatiotemporal clustering of the diseases. Results:A total of 1 822 cases of foodborne infection of V. parahaemolyticus were reported in Ningbo from 2014 to 2022, with an overall positive rate of 3.78%. Spatial autocorrelation analysis showed that the positive rate of foodborne infection of V. parahaemolyticus in Ningbo was unevenly distributed from 2014 to 2022, Ninghai was a high-high clustering area, while Zhenhai was a high-low clustering area, and Jiangbei was a low-low clustering area. The annual incidence was high during July-September. Spatiotemporal scanning analysis found one class Ⅰ spatiotemporal clustering area and three class Ⅱ spatiotemporal clustering areas, with the class Ⅰ spatiotemporal clustering area being observed in Jiangbei and Zhenhai from 2019 to 2022. Conclusions:Spatiotemporal clustering of foodborne infection of V. parahaemolyticus existed in Ningbo from 2014 to 2022, with an annual high incidence period from July to September. The key areas for the prevention and control of foodborne infection of V. parahaemolyticus are coastal districts (counties, cities) in Ningbo.
4.Early experience with mechanical hemodynamic support for catheter ablation of malignant ventricular tachycardia
Mengmeng LI ; Yang YANG ; Deyong LONG ; Chenxi JIANG ; Ribo TANG ; Caihua SANG ; Wei WANG ; Xin ZHAO ; Xueyuan GUO ; Songnan LI ; Changyi LI ; Man NING ; Changqi JIA ; Li FENG ; Dan WEN ; Hui ZHU ; Yuexin JIANG ; Fang LIU ; Tong LIU ; Jianzeng DONG ; Changsheng MA
Chinese Journal of Cardiology 2024;52(7):768-776
Objective:To explore the role of mechanical hemodynamic support (MHS) in mapping and catheter ablation of patients with hemodynamically unstable ventricular tachycardia (VT), report single-center experience in a cohort of consecutive patients receiving VT ablation during MHS therapy, and provide evidence-based medical evidence for clinical practice.Methods:This was a retrospective cohort study. Patients with hemodynamically unstable VT who underwent catheter ablation with MHS at Beijing Anzhen Hospital, Capital Medical University between August 2021 and December 2023 were included. Patients were divided into rescue group and preventive group according to the purpose of treatment. Their demographic data, periprocedural details, and clinical outcomes were collected and analyzed.Results:A total of 15 patients with hemodynamically unstable VT were included (8 patients in the rescue group and 7 patients in the preventive group). The acute procedure was successful in all patients. One patient in the rescue group had surgical left ventricular assist device (LVAD) implantation, remaining 14 patients received extracorporeal membrane oxygenation (ECMO) for circulation support. ECMO decannulation was performed in 12 patients due to clinical and hemodynamic stability, of which 6 patients were decannulation immediately after surgery and the remaining patients were decannulation at 2.0 (2.5) d after surgery. Two patients in the rescue group died during the index admission due to refractory heart failure and cerebral hemorrhage. During a median follow-up of 30 d (1 d to 12 months), one patient with LVAD had one episode of ventricular fibrillation at 6 months after discharge, and no further episodes of ventricular fibrillation and/or VT occurred after treatment with antiarrhythmic drugs. No malignant ventricular arrhythmia occurred in the remaining 12 patients who were followed up.Conclusions:MHS contributes to the successful completion of mapping and catheter ablation in patients with hemodynamically unstable VT, providing desirable hemodynamic status for emergency and elective conditions.
5.Multicenter retrospect analysis of early clinical features and analysis of risk factors on prognosis of elderly patients with severe burns
Qimin MA ; Wenbin TANG ; Xiaojian LI ; Fei CHANG ; Xi YIN ; Zhaohong CHEN ; Guohua WU ; Chengde XIA ; Xiaoliang LI ; Deyun WANG ; Zhigang CHU ; Yi ZHANG ; Lei WANG ; Choulang WU ; Yalin TONG ; Pei CUI ; Guanghua GUO ; Zhihao ZHU ; Shengyu HUANG ; Liu CHANG ; Rui LIU ; Yongji LIU ; Yusong WANG ; Xiaobin LIU ; Tuo SHEN ; Feng ZHU
Chinese Journal of Burns 2024;40(3):249-257
Objective:To investigate the early clinical characteristics of elderly patients with severe burns and the risk factors on prognosis.Methods:This study was a retrospective case series study. Clinical data of 124 elderly patients with severe burns who met the inclusion criteria and were admitted to the 12 hospitals from January 2015 to December 2020 were collected, including 4 patients from the Fourth People's Hospital of Dalian, 5 patients from Fujian Medical University Union Hospital, 22 patients from Guangzhou Red Cross Hospital of Jinan University, 5 patients from Heilongjiang Provincial Hospital, 27 patients from the First Affiliated Hospital of Naval Medical University, 9 patients from the First Affiliated Hospital of Nanchang University, 10 patients from Affiliated Hospital of Nantong University, 9 patients from Tongren Hospital of Wuhan University & Wuhan Third Hospital, 12 patients from the 924 th Hospital of PLA, 6 patients from Zhangjiagang First People's Hospital, 4 patients from Taizhou Hospital of Zhejiang Province, and 11 patients from Zhengzhou First People's Hospital. The patients' overall clinical characteristics, such as gender, age, body mass index, total burn area, full-thickness burn area, inhalation injury, causative factors, whether combined with underlying medical diseases, and admission time after injury were recorded. According to the survival outcome within 28 days after injury, the patients were divided into survival group (89 cases) and death group (35 cases). The following data of patients were compared between the two groups, including the basic data and injuries (the same as the overall clinical characteristics ahead); the coagulation indexes within the first 24 hours of injury such as prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time, D-dimer, fibrinogen degradation product (FDP), international normalized ratio (INR), and fibrinogen; the blood routine indexes within the first 24 hours of injury such as white blood cell count, platelet count, neutrophil-to-lymphocyte ratio, monocyte count, red blood cell count, hemoglobin, and hematocrit; the organ function indexes within the first 24 hours of injury such as direct bilirubin, total bilirubin, urea, serum creatinine, aspartate aminotransferase, alanine aminotransferase, total protein, albumin, globulin, blood glucose, triglyceride, total cholesterol, alkaline phosphatase, creatine kinase, electrolyte indexes (potassium, sodium, chlorine, calcium, magnesium, and phosphorus in blood), uric acid, myoglobin, and brain natriuretic peptide; the infection and blood gas indexes within the first 24 hours of injury such as procalcitonin, C-reactive protein, pH value, oxygenation index, base excess, and lactate; treatment such as whether conducted with mechanical ventilation, whether conducted with continuous renal replacement therapy, whether conducted with anticoagulation therapy, whether applied with vasoactive drugs, and fluid resuscitation. The analysis was conducted to screen the independent risk factors for the mortality within 28 days after injury in elderly patients with severe burns. Results:Among 124 patients, there were 82 males and 42 females, aged 60-97 years, with body mass index of 23.44 (21.09, 25.95) kg/m 2, total burn area of 54.00% (42.00%, 75.00%) total body surface area (TBSA), and full-thickness burn area of 25.00% (10.00%, 40.00%) TBSA. The patients were mainly combined with moderate to severe inhalation injury and caused by flame burns. There were 43 cases with underlying medical diseases. The majority of patients were admitted to the hospital within 8 hours after injury. There were statistically significant differences between patients in the 2 groups in terms of age, total burn area, full-thickness burn area, and inhalation injury, and PT, APTT, D-dimer, FDP, INR, white blood cell count, platelet count, urea, serum creatinine, blood glucose, blood sodium, uric acid, myoglobin, and urine volume within the first 24 hours of injury (with Z values of 2.37, 5.49, 5.26, 5.97, 2.18, 1.95, 2.68, 2.68, 2.51, 2.82, 2.14, 3.40, 5.31, 3.41, 2.35, 3.81, 2.16, and -3.82, respectively, P<0.05); there were statistically significant differences between two groups of patients in whether conducted with mechanical ventilation and whether applied with vasoactive drugs (with χ2 values of 9.44 and 28.50, respectively, P<0.05). Age, total burn area, full-thickness burn area, serum creatinine within the first 24 hours of injury, and APTT within the first 24 hours of injury were the independent risk factors for the mortality within 28 days after injury in elderly patients with severe burns (with odds ratios of 1.17, 1.10, 1.10, 1.09, and 1.27, 95% confidence intervals of 1.03-1.40, 1.04-1.21, 1.05-1.19, 1.05-1.17, and 1.07-1.69, respectively, P<0.05). Conclusions:The elderly patients with severe burns had the injuries mainly from flame burns, often accompanied by moderate to severe inhalation injury and enhanced inflammatory response, elevated blood glucose levels, activated fibrinolysis, and impaired organ function in the early stage, which are associated with their prognosis. Age, total burn area, full-thickness burn area, and serum creatinine and APTT within the first 24 hours of injury are the independent risk factors for death within 28 days after injury in this population.
6.AI-HIP system for prosthesis size,global femoral offset and osteotomy in total hip arthroplasty
Guo-Yuan SUN ; Yan-Kun JIANG ; Tong LI ; Xue-Feng CONG ; Cheng HUANG ; Ran DING ; Wei-Guo WANG ; Qi-Dong ZHANG
China Journal of Orthopaedics and Traumatology 2024;37(9):848-854
Objective To explore planning effect of AI-HIP assisted surgical planning system in primary unilateral total hip arthroplasty(THA)and its influence on clinical outcomes.Methods A retrospective analysis was conducted on clinical data of 36 patients who underwent their first unilateral THA from March 2022 to November 2022 and continuously used AI-HIP system(AI-HIP group),including 16 males and 20 females,aged from 43 to 81 years old with an average of(62.2±10.9)years old.According to the matching principle,36 patients who were planned by the traditional template method at the same period were selected as the control group,including 16 males and 20 females,aged from 40 to 80 years old with an average of(60.9±12.1)years old.The accuracy between two groups of prostheses were compared,as well as the combined eccentricity difference between preoperative planning and postoperative practice,lower limb length difference,osteotomy height from the upper edge of the lesser trochanter and top shoulder distance to evaluate planning effect.Harris score and visual analogue scale(VAS)were used to evaluate clinical efficacy.Results Both groups were followed up for 12 to 18 months with an average of(14.5±2.1)months.The complete accuracy and approximate accuracy of acetabular cup and femoral stalk prosthesis in AI-HIP group were 72.2%,100%,58.3%,88.9%,respectively,which were better than 44.4%,83.3%,33.3%,66.7%in control group(P<0.05).There was no statistical significance in planning of femoral head prosthesis size(P>0.05).The actual combined eccentricity difference and combined eccentricity difference(practical-planning)in Al-HIP group were 1.0(0.2,2.4)mm and 1.1(-2.1,3.2)mm,respectively;which were better than 3.0(1.4,4.9)mm and 3.5(-1.6,6.5)mm in control group(P<0.05).There was no significant difference between two groups in actual osteotomy height of the upper margin of the lesser trochanter(P>0.05).In AI-HIP group,the actual difference of lower extremity length after surgery,the difference of lower extremity length(practical-planning),osteotomy height from the upper margin of lesser trochanter(practical-planning),actual topshoulder distance after surgery,and topshoulder distance(practical-planning)were 1.5(0.2,2.8),1.1(-0.3,2.2),2.1(-2.3,4.1),(15.3±4.1),2.2(-4.8,0.3)mm,respectively;which were better than control group of 2.6(1.3,4.1),2.5(0.3,3.8),5.8(-2.4,7.7),(13.0±4.3),-5.7(-9.4,-2.2)mm(P<0.05).At final follow-up,there were no significant differences in Harris scores of pain,function,deformity,total scores and VAS between two groups(P>0.05).The range of motion score was 4.8±0.6 in AI-HIP group,which was higher than that in control group(4.4±0.8)(P<0.05).Conclusion Compared with traditional template planning,AI-HIP assisted surgical planning system has good accuracy in predicting the prosthetic size of the acetabular cup and femoral stalk,restor-ing joint eccentricity,planning lower limb length,osteotomy height and top shoulder distance on the first unilateral THA,and the clinical follow-up effect is satisfactory.
7.Epidemiological characteristics of carbapenem-resistant Klebsiella pneumoniae infection in adult inpatients
Journal of Public Health and Preventive Medicine 2023;34(5):95-98
Objective To analyze the epidemiological characteristics of carbapenem-resistant Klebsiella pneumoniae (CRKP) in adult inpatients, and to provide a theoretical basis for the diagnosis and treatment of CRKP. Methods A total of 753 hospitalized patients with Klebsiella pneumoniae (KPN) infection in our hospital from 2017 to 2021 were selected as the investigation subjects. According to the sensitivity to carbapenem drugs, the patients were divided into carbapenem sensitive Klebsiella pneumoniae (CSKP) group (n=638) and CRKP group (n=115). The age, gender, department distribution, underlying diseases, length of hospital stay, use of antibiotics and other clinical data of all subjects were analyzed by self-made survey scale of our hospital. Univariate analysis and logistic regression analysis were used to analyze the risk factors of CRKP nosocomial infection in adult inpatients. Results Among of 753 KPN patients, 115 cases (15.27%) were detected with CRKP, including 87 males and 28 females. The detection rate of CRKP in different age groups was significantly different (P<0.05). The detection rate of CRKP in the age group of >60 years was significantly higher than that in the age group of 41-60 years, 21-40 years, and 16-20 years (P<0.05). The detection rate of CRKP increased year by year from 2017 to 2021, and the difference was statistically significant (P<0.05). There was no significant difference between the detection rate of CRKP in spring and winter (66/459) and that in summer and autumn (49/294) (χ2 value =0.725, P>0.05). CRKP strains were mainly isolated from oral and maxillofacial surgery (19.13%), infection department (15.65%), geriatric department (15.65%), and ICU (14.78%). The detection rate of CRKP in different pathogenic bacteria samples was different, including sputum (19.40%), urine (15.43%) and blood (12.58%), with statistically significant difference (P<0.05) The respiratory tract sputum specimens were all expectoration. There were significant differences in age, gender, use of carbapenems ≥7 days, invasive procedures, use of antibiotics ≥2 kinds, use of antibiotics ≥14 days, and use of enzyme inhibitors ≥7 days between the CSKP group and the CRKP group (P<0.05). Antimicrobial application time ≥14 days (OR=5.412), invasive operation (OR=6.431), and carbapenem use ≥7 days (OR=5.417) were the risk factors for CRKP nosocomial infection in adult inpatients (P<0.05). Conclusion Nosocomial infection of CRKP occurs mostly in elderly ICU patients. Intervention measures should be given to adult inpatients who have used antibiotics for ≥14 days, invasive procedures, and carbapenem antibiotics for ≥7 days, which can reduce the risk of CRKP infection in inpatients.
8.Recovery of proprioception after lateral ankle sprain
Renjie XU ; Zhou LI ; Yuting GUO ; Xiqin YU ; Jingming MA ; Xiangyang GE ; Ziyun ZHU ; Yuxin ZHANG ; Feng ZHOU
Chinese Journal of Rehabilitation Theory and Practice 2023;29(7):844-848
ObjectiveTo observe the recovery of proprioception of the affected ankle over time after lateral ankle sprain accepting routine rehabilitation. MethodsFrom June, 2020 to June, 2022, 18 patients with lateral ankle sprain in Kunshan Rehabilitation Hospital underwent routine rehabilitation for twelve weeks. They were measured active and passive position sense of bilateral ankles using an isokinetic dynamometer before treatment, and four, eight and twelve weeks after treatment, respectively. ResultsThe active presentation difference of affected ankle reduced after treatment (F = 22.533, P < 0.001), but it was more than that of the healthy ankle at the same time (t > 4.419, P < 0.001). No significant improvement was found in passive presentation difference of affected ankle after treatment (F = 1.175, P > 0.05), and it was not significantly different from those of the healthy ankle at the same time (|t| < 0.646, P > 0.05). ConclusionProprioception of affected ankle has been impaired after lateral ankle sprain, and it can be recovered after rehabilitation, but cannot achieve the healthy level even after three months of training. Passive position sense as an index of proprioception needs more researches.
9.Development and validation of a score predicting mortality for older patients with mitral regurgitation.
De-Jing FENG ; Yun-Qing YE ; Zhe LI ; Bin ZHANG ; Qing-Rong LIU ; Wei-Wei WANG ; Zhen-Yan ZHAO ; Zheng ZHOU ; Qing-Hao ZHAO ; Zi-Kai YU ; Hai-Tong ZHANG ; Zhen-Ya DUAN ; Bin-Cheng WANG ; Jun-Xing LV ; Shuai GUO ; Run-Lin GAO ; Hai-Yan XU ; Yong-Jian WU
Journal of Geriatric Cardiology 2023;20(8):577-585
OBJECTIVE:
To develop and validate a user-friendly risk score for older mitral regurgitation (MR) patients, referred to as the Elder-MR score.
METHODS:
The China Senile Valvular Heart Disease (China-DVD) Cohort Study functioned as the development cohort, while the China Valvular Heart Disease (China-VHD) Study was employed for external validation. We included patients aged 60 years and above receiving medical treatment for moderate or severe MR (2274 patients in the development cohort and 1929 patients in the validation cohort). Candidate predictors were chosen using Cox's proportional hazards model and stepwise selection with Akaike's information criterion.
RESULTS:
Eight predictors were identified: age ≥ 75 years, body mass index < 20 kg/m2, NYHA class III/IV, secondary MR, anemia, estimated glomerular filtration rate < 60 mL/min per 1.73 m2, albumin < 35 g/L, and left ventricular ejection fraction < 60%. The model displayed satisfactory performance in predicting one-year mortality in both the development cohort (C-statistic = 0.73, 95% CI: 0.69-0.77, Brier score = 0.06) and the validation cohort (C-statistic = 0.73, 95% CI: 0.68-0.78, Brier score = 0.06). The Elder-MR score ranges from 0 to 15 points. At a one-year follow-up, each point increase in the Elder-MR score represents a 1.27-fold risk of death (HR = 1.27, 95% CI: 1.21-1.34, P < 0.001) in the development cohort and a 1.24-fold risk of death (HR = 1.24, 95% CI: 1.17-1.30, P < 0.001) in the validation cohort. Compared to EuroSCORE II, the Elder-MR score demonstrated superior predictive accuracy for one-year mortality in the validation cohort (C-statistic = 0.71 vs. 0.70, net reclassification improvement = 0.320, P < 0.01; integrated discrimination improvement = 0.029, P < 0.01).
CONCLUSIONS
The Elder-MR score may serve as an effective risk stratification tool to assist clinical decision-making in older MR patients.
10.Immunogenicity of mucosal COVID-19 vaccine candidates based on the highly attenuated vesicular stomatitis virus vector (VSVMT) in golden syrian hamster.
Yong KE ; En ZHANG ; Jianming GUO ; Xiaoxiao ZHANG ; Lei WANG ; Duo CHEN ; Xinkui FANG ; Jianwei ZHU ; Feng LI ; Tao SUN ; Baohong ZHANG
Acta Pharmaceutica Sinica B 2023;13(12):4856-4874
COVID-19 is caused by coronavirus SARS-CoV-2. Current systemic vaccines generally provide limited protection against viral replication and shedding within the airway. Recombinant VSV (rVSV) is an effective vector which inducing potent and comprehensive immunities. Currently, there are two clinical trials investigating COVID-19 vaccines based on VSV vectors. These vaccines were developed with spike protein of WA1 which administrated intramuscularly. Although intranasal route is ideal for activating mucosal immunity with VSV vector, safety is of concern. Thus, a highly attenuated rVSV with three amino acids mutations in matrix protein (VSVMT) was developed to construct safe mucosal vaccines against multiple SARS-CoV-2 variants of concern. It demonstrated that spike protein mutant lacking 21 amino acids in its cytoplasmic domain could rescue rVSV efficiently. VSVMT indicated improved safeness compared with wild-type VSV as the vector encoding SARS-CoV-2 spike protein. With a single-dosed intranasal inoculation of rVSVΔGMT-SΔ21, potent SARS-CoV-2 specific neutralization antibodies could be stimulated in animals, particularly in term of mucosal and cellular immunity. Strikingly, the chimeric VSV encoding SΔ21 of Delta-variant can induce more potent immune responses compared with those encoding SΔ21 of Omicron- or WA1-strain. VSVMT is a promising platform to develop a mucosal vaccine for countering COVID-19.


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