Human Milk Oligosaccharides Enhance Innate Immunity to Respiratory Syncytial Virus and Influenza <i>in Vitro</i>

Human milk oligosaccharides (HMO) contribute to innate immunity by enhancing growth of beneficial bacteria, epithelial cell maturation and mucosal barrier integrity. They have immunomodulatory effects and can block pathogen binding to host cell surface glycans or receptors. We investigated the effects of 2’-fucosyllactose (2’FL), 6’-sialyllactose (6’SL), 3’-sialyllactose (3’SL) and lacto-N-neoTetraose (LNnT) on human respiratory epithelial cell lines or peripheral blood mononuclear cells (PBMCs) following respiratory viral infectionin vitro. Expression of cytokines and viral load were monitored in infected cells. These biomarkers of innate immunity were selected since viral load and cytokine levels (IP-10, MIP-1α, IL-6, IL-8, TNF-α) have been correlated with disease severity in respiratory syncytial virus (RSV) and influenza (IAV) virus infectionin vivo. 2’FL significantly decreased RSV viral load and cytokines associated with disease severity (IL-6, IL-8, MIP-1α) and inflammation (TNF-α, MCP-1) in airway epithelial cells. LNnT and 6’SL significantly decreased IAV viral load in airway epithelial cells. 6’SL dose-dependently down-regulated IP-10 and TNF-α in RSV infected PBMCs. HMO at or below levels found in breast milk enhance innate immunity to respiratory viruses in vitro and may interact directly with cells to modulate biomarkers of innate immunity.

In vitro study on the antiviral activity of 9 extracts of traditional Chinese herbal medicine against the human respiratory syncytial virus

Objective:To study the in vitro virucidal activity of 9 extracts of traditional Chinese herbal medicine(the water extracts of Evodia lepta,Clausena lansium,Clerodendrum cyrtophyllum,Callicarpa nudiflora,Nauclea officinalis and Elaeagnus gonyanthes,the alcohol extracts of Nauclea officinalis,Elaeagnus gonyanthes and Zanthoxylumarmatum)on human respiratory syncytial virus(HRSV).Methods:The cytotoxic effect of the extracts on cells was evaluated by a cell viability assay using the CCK-8 method,a concentration of the extracts with cell viability greater than 50%was selected for the follow-up anti-HRSV effect assay,the 50%effective concentration(EC50)was assessed by an in vitro cell infection model.Results:The EC50s of the water extract from Clerodendrum cyrtophyllum,Callicarpa nudiflora and Elaeagnus gonyanthes were 0.05 mg/mL,0.03 mg/mL and 0.05 mg/mL,and the therapeutic index(TI)of them were 18.60,21.67 and 56.80 respectively.Conclusion:The water extracts of Clerodendrum cyrtophyllum,Callicarpa nudiflora and Elaeagnus gonyanthes possess the activity of anti-HRSV virus.

Genetic Characterization of Fusion Protein of Human Respiratory Syncytial Virus: Beijing

Objective Fusion protein is a subunit of the human respiratory syncytial virus(HRSV)and a potential vaccine candidate.Thus,a study on the genetic characteristics of F protein was considered important for further investigations in this field.The aim of this study was to determine the prevalence and genetic diversity of the F gene of HRSV infections in hospitalized pediatric patients in Beijing with acute lower respiratory tract infections and to compare the circulating genotypes that are currently found worldwide.Methods HRSV particles were amplified by RT-PCR and the PCR products were purified for sequencing.Further analysis was carried out by Bioedit and MEGA 3.0 biological software programs.Results Seventy-six samples(23.1%)were positive for HRSV.The percentage of cases in patients younger than 1year was 84.21%.Among the six Beijing isolates,four belonged to subgroup A,whose respective F genes shared97.0%-97.4%nucleotide sequence identity and 92.1%-93.0%amino acid sequence identity.The other two isolates belonged to subgroup B.Here,97.3%and 98.2%sequence identity were found at nucleotide and amino acid levels,respectively.Conclusions Phylogenetic analysis of nucleotide sequences revealed that those four isolates within subgroup A were monophyletic and closely related to each other,but those two within subgroup B distributed in two distinct clusters.Subgroup A and B strains co-circulated,indicating that two different transmission chains occurred in Beijing from 2003-2004.

Efficacy and mechanisms of Traditional Chinese Medicine prevention and treatment for respiratory viruses

Respiratory virus infection was the most common viral infection in clinical practice with the greatest impact,including the Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),posing a huge threat to the world's public health and human life safety.Commonly used antiviral drugs have obvious side effects and a narrow scope of application.Respiratory viruses are susceptible to infection,mutation,and prevalence,which also pose challenges to traditional antiviral drugs and vaccine development.Traditional Chinese Medicine(TCM)has a long history of treating infectious diseases,with many herbs and compounds.Its multi-component,multi-target and multi-path characteristics have made it have great advantages and potential in the development of new anti-respiratory virus drugs.This review summarized TCM for the prevention and treatment of common respiratory viruses,and provided new strategies for the research and development of new TCM antiviral drugs and for responding to infectious respiratory virus diseases.

A multi-center study on genetic variations in the fusion protein of respiratory syncytial virus from children with Acute Lower Respiratory Tract Infections in China during 2017-2021

Respiratory syncytial virus(RSV)is a significant cause of acute lower respiratory tract infection(ALRTI)in children underfive years of age.Between 2017 and 2021,396 complete sequences of the RSV F gene were obtained from 500 RSV-positive throat swabs collected from ten hospitals across nine provinces in China.In addition,151 sequences from China were sourced from GenBank and GISAID,making a total of 549 RSV F gene sequences subjected to analysis.Phylogenetic and genetic diversity analyses revealed that the RSV F genes circulating in China from 2017 to 2021 have remained relatively conserved,although some amino acids(AAs)have undergone changes.AA mutations with frequencies10%were identified at six sites and the p27 region:V384I(site I),N276S(site II),R213S(siteØ),and K124N(p27)for RSV A;F45L(site I),M152I/L172Q/S173 L/I185V/K191R(site V),and R202Q/I206M/Q209R(siteØ)for RSV B.Comparing mutational frequencies in RSV-F before and after 2020 revealed minor changes for RSV A,while the K191R,I206M,and Q209R frequencies increased by over 10%in RSV B.Notably,the nirsevimab-resistant mutation,S211N in RSV B,increased in frequency from 0%to 1.15%.Both representative strains aligned with the predicted RSV-F structures of their respective prototypes exhibited similar conformations,with low root-mean-square deviation values.These results could provide foundational data from China for the development of RSV mAbs and vaccines.

A multi-center study on Molecular Epidemiology of Human Respiratory Syncytial Virus from Children with Acute Lower Respiratory Tract Infections in the Mainland of China between 2015 and 2019

Human respiratory syncytial virus(RSV) is a major pathogen of acute lower respiratory tract infection among young children. To investigate the prevalence and genetic characteristics of RSV in China, we performed a molecular epidemiological study during 2015–2019. A total of 964 RSV-positive specimens were identified from 5529 enrolled patients during a multi-center study. RSV subgroup A(RSV-A) was the predominant subgroup during this research period except in2016. Totally, 535 sequences of the second hypervariable region(HVR-2) of the G gene were obtained. Combined with182 Chinese sequences from GenBank, phylogenetic trees showed that 521 RSV-A sequences fell in genotypes ON1(512),NA1(6) and GA5(3), respectively;while 196 RSV-B sequences fell in BA9(193) and SAB4(3). ON1 and BA9 were the only genotypes after December 2015. Genotypes ON1 and BA9 can be separated into 10 and 7 lineages, respectively. The HVR-2 of genotype ON1 had six amino acid changes with a frequency more than 10%, while two substitutions H258 Q and H266 L were co-occurrences. The HVR-2 of genotype BA9 had nine amino acid substitutions with a frequency more than10%, while the sequences with T290 I and T312 I were all from 2018 to 2019. One N-glycosylation site at 237 was identified among ON1 sequences, while two N-glycosylation sites(296 and 310) were identified in the 60-nucleotide duplication region of BA9. To conclusion, ON1 and BA9 were the predominant genotypes in China during 2015–2019. For the genotypes ON1 and BA9, the G gene exhibited relatively high diversity and evolved continuously.

Evaluation of the Safety and Immune Efficacy of Recombinant Human Respiratory Syncytial Virus Strain Long Live Attenuated Vaccine Candidates

Human respiratory syncytial virus(RSV)infection is the leading cause of lower respiratory tract illness(LRTI),and no vaccine against LRTI has proven to be safe and effective in infants.Our study assessed attenuated recombinant RSVs as vaccine candidates to prevent RSV infection in mice.The constructed recombinant plasmids harbored(5′to 3′)a T7 promoter,hammerhead ribozyme,RSV Long strain antigenomic cDNA with cold-passaged(cp)mutations or cp combined with temperature-sensitive attenuated mutations from the A2 strain(A2cpts)or further combined with SH gene deletion(A2cptsΔSH),HDV ribozyme(δ),and a T7 terminator.These vectors were subsequently co-transfected with four helper plasmids encoding N,P,L,and M2-1 viral proteins into BHK/T7-9 cells,and the recovered viruses were then passaged in Vero cells.The rescued recombinant RSVs(rRSVs)were named rRSV-Long/A2cp,rRSV-Long/A2cpts,and rRSV-Long/A2cptsΔSH,respectively,and stably passaged in vitro,without reversion to wild type(wt)at sites containing introduced mutations or deletion.Although rRSV-Long/A2cpts and rRSV-Long/A2cptsΔSH displayed temperature-sensitive(ts)phenotype in vitro and in vivo,all rRSVs were significantly attenuated in vivo.Furthermore,BALB/c mice immunized with rRSVs produced Th1-biased immune response,resisted wtRSV infection,and were free from enhanced respiratory disease.We showed that the combination ofΔSH with attenuation(att)mutations of cpts contributed to improving att phenotype,efficacy,and gene stability of rRSV.By successfully introducing att mutations and SH gene deletion into the RSV Long parent and producing three rRSV strains,we have laid an important foundation for the development of RSV live attenuated vaccines.

An RNA polymerase I-driven human respiratory syncytial virus minigenome as a tool for quantifying virus titers and screening antiviral drug

Human respiratory syncytial virus（RSV） is an important pediatric pathogen of lower respiratory tract worldwide. No vaccines and antiviral drugs are available. Herein the use of an RNA polymerase I-driven RSV minigenome for analyzing RSV replication and screening anti-RSV drugs was investigated. The RNA polymerase I（Pol I） was used to transcribe RSV minigenome from the constructed plasmid, designated p HM-RSV-Gluc, of minigenome c DNA which comprised trailer region, gene start sequence（GS）, reverse complementary copy of Gaussia luciferase（Gluc） gene, gene end sequence（GE）, and leader region in the direction of 5＇–3＇end and was flanked by promoter and terminator of Pol I. The expression of Gluc was confirmed in p HM-RSV-Gluc transfected HEp-2 cells following RSV infection and had the characteristics of dose-dependent, which provided a rapid, sensitive, and quantitative method for quantifying virus titers and screening antiviral drugs.

更昔洛韦联合雾化重组人干扰素α1b治疗对呼吸道合胞病毒感染肺炎患儿炎症因子及免疫功能的影响

目的:分析更昔洛韦联合雾化重组人干扰素α1b治疗对呼吸道合胞病毒感染肺炎患儿炎症因子及免疫功能的影响。方法:选取本院收治的呼吸道合胞病毒感染肺炎患儿100例作为研究对象。根据随机数表法分为对照和观察两组,各50例;比较两组治疗前、后的炎性因子降钙素原(PCT)、白介素-6(IL-6)、C反应蛋白(CRP)与免疫球蛋白IgA、IgG、IgM水平,详细记录症状体征消失时间并分析治疗期间发生的不良症状。结果:治疗后两组比较,观察组持续发热、咳嗽、憋喘以及肺啰音消失时间短(P<0.05),血清PCT、IL-6与CRP水平低(P<0.05),血清IgG、IgA、IgM水平明显升高(P<0.05);治疗期间,两组恶心呕吐、白细胞降低、皮疹的总发生率比较无统计学意义(P>0.05)。结论:对呼吸道合胞病毒感染肺炎患儿实施更昔洛韦联合雾化重组人干扰素α1b联合用药可缩短症状体征消失时间,减轻机体炎症反应,提高机体免疫力,安全性相对较好。

人原代呼吸道上皮细胞培养及抗呼吸道合胞病毒活性

为建立人原代呼吸道上皮细胞(Human airway epithelial cell,hAEC)的培养方法,并在hAEC体系上探讨3-硫代吲哚类化合物RSV-A-4和免疫抑制剂代谢产物6-MMPr的抗呼吸道合胞病毒(Respiratory syncytial virus,RSV)活性及其机制,从而构建可用于RSV药物筛选及药效评价的细胞模型。采集人呼吸道上皮细胞样本,分离细胞后建立hAEC的培养方法,并进行细胞形态和活力鉴定;在hAEC体系上检测小分子化合物RSV-A-4和6-MMPr的抗RSV活性及其细胞毒性;采用实时荧光定量PCR(RT-qPCR)与Time-of-addition assay技术,探讨RSV-A-4和6-MMPr的抑制RSV复制的作用机制。培养的hAEC经鉴定:其体外培养存活率可达93.51%;RSV-A-4和6-MMPr的半数抑制浓度(Half maximal inhibitory concentration,IC_(50))分别为(207.30±4.77)μmol/L和(3191.00±6.11)μmol/L,6-MMPr的半数细胞毒性浓度(Half maximal cytotoxic concentration,CC_(50))为(95526.00±10.97)μmol/L,而RSV-A-4对hAEC未见明显细胞毒性;RSV-A-4和6-MMPr均在RSV病毒基因组复制阶段抑制RSV复制。成功建立可用于抗RSV药物筛选及体外评价的hAEC培养体系,RSV-A-4和6-MMPr在细胞水平均能有效抑制RSV复制。

布地奈德结合重组人干扰素α1b雾化吸入对RSV毛细支气管炎患儿肺功能指标的影响探讨

目的 探究对呼吸道合胞病毒(RSV)毛细支气管炎患儿应用布地奈德结合重组人干扰素α1b雾化吸入的效果及对其肺功能指标的影响。方法 选取92例RSV毛细支气管炎患儿,采用Excel表格分组法分为实验组与参照组,每组46例。参照组给予基础方案治疗,实验组给予布地奈德结合重组人干扰素α1b雾化吸入治疗。比较两组治疗效果、症状与体征消失时间、肺功能指标[潮气量(TV)、呼气峰流速(PEF)、达峰时间比(TPTEF/TE)及达峰容积比(VPTEF/VE)]及炎性因子[白细胞介素-10(IL-10)及干扰素-γ(INF-γ)]水平。结果 实验组治疗总有效率97.83%高于参照组的86.96%,组间对比差异成立(P<0.05)。实验组症状与体征消失时间中肺部啰音、三凹征、喘息、咳嗽消失时间分别为(4.65±0.88)、(2.96±0.52)、(3.70±1.08)、(5.18±1.30)d,均短于参照组的(5.41±1.13)、(4.20±0.87)、(4.22±0.96)、(2.79±1.24)d,组间对比差异成立(P<0.05)。实验组肺功能指标中TV、PEF、TPTEF/TE及VPTEF/VE分别为(7.51±1.29)ml/kg、(5.73±1.54)L/s、(26.91±7.08)%、(29.84±5.33)%,均高于参照组的(6.35±1.47)ml/kg、(4.02±0.83)L/s、(23.25±6.46)%、(26.91±4.32)%,组间对比差异成立(P<0.05)。实验组炎性因子指标中IL-10及INF-γ水平分别为(28.06±5.37)、(38.25±6.43)ng/L,均高于参照组的(15.64±7.22)、(29.36±5.24)ng/L,组间对比差异成立(P<0.05)。结论 布地奈德结合重组人干扰素α1b雾化吸入治疗RSV毛细支气管炎患儿的效果较好,临床症状与体征消失时间短,肺功能指标及炎性因子水平改善明显,具有重要临床应用价值。

IL2rg^(-/-)大鼠支持人RSV在体内的长期感染

目的为了克服已有人呼吸道合胞病毒(human respiratory syncytial virus,hRSV)动物模型的局限性,如半受纳性和感染持续时间短,本文利用TALEN基因编辑技术建立了IL2rg基因敲除(IL2rg^(-/-))的大鼠模型。方法用hRSV滴鼻感染该动物模型,观察感染期(0~35 d)的临床表征、体重及体温变化;记录不同时间点(滴鼻感染后第4、11、20、35天)鼻腔、气管、肺等呼吸道脏器的病毒总拷贝数;在观察终点(滴鼻感染后第35天)对感染动物的靶器官进行病理分析;观察不同时间点(滴鼻感染后第4、20、35天)外周血T、B、NK、NKT细胞的变化及不同时间点多种细胞因子的变化。结果(1)通过鼻内接种hRSV后,纯合的IL2rg基因敲除大鼠的呼吸道内能保持较高的病毒载量,鼻腔中病毒的平均峰值滴度能快速升至1×10^(10 )copies/g,至第5周时,病毒依然能维持复制,病毒载量亦可达到1×10^(7)copies/g。(2)但其鼻、气管和肺组织,无明显病变。(3)感染hRSV的IL2rg^(-/-)大鼠外周血B细胞含量有上升。(4)IL-6和MCP-1两种细胞因子都在感染前期上升,在观察终点回落。结论本研究基于TALEN技术建立了IL2rg^(-/-)大鼠模型,并发现该模型能很好地支持hRSV高水平复制和并长期感染,为抗病毒药物筛选、抗hRSV抗体体内效力评价,提供了良好的动物模型。

呼吸道合胞病毒、人偏肺病毒和流感病毒的感染特点分析及成人感染住院的相关因素分析

目的比较呼吸道合胞病毒(RSV)、人偏肺病毒(hMPV)和流感感染特点并分析成人感染住院的相关因素。方法收集2021年1月-2023年1月在流感/RSV/hMPV流行季节期间住院治疗的急性呼吸道感染的成年患者共202例,其中流感组104例,RSV组68例,MPV30例。比较三组的临床感染特征,并使用Logistics回归分析成人感染住院的相关危险因素。结果与流感患者相比,RSV和hMPV患者有更多的潜在风险因素,包括年龄大于65岁,合并症如心脏疾病、肾脏疾病、COPD更多。RSV患者住院前出现症状的时间最长,住院时间最长,入住重症监护室的比例最高,住院期间接受氧气补充的概率更高。多因素Logistics回归分析显示年龄≥65岁(调整OR=3.19,95%CI=1.44~4.17,P=0.034)、合并慢性心脏疾病(调整OR=2.01,95%CI=1.98~5.42,P=0.012)、合并慢性肾脏疾病(调整OR=2.12,95%CI=1.45~4.34,P=0.001)、合并COPD(调整OR=2.26,95%CI=0.78~3.23,P=0.122)、重度COPD(调整OR=1.85,95%CI=1.21~2.93,P=0.016)、治疗时出现COPD加重(整调OR=1.87,95%CI=1.46~5.32,P=0.015)、出现败血症(调整OR=2.12,95%CI=0.93~4.87,P=0.001)为成人住院的危险因素。结论虽然流感的发病率更高,但在住院成人中,RSV和hMPV的潜在风险因素更多,住院时间更长,这表明需要采取有效的干预措施。与流感、RSV、hMPV成人患者住院相关的危险因素为年龄≥65岁,患者合并慢性心脏疾病、慢性肾脏疾病、重度COPD,治疗时COPD加重、出现败血症。

重组人干扰素α-1b联合布地奈德雾化对合胞病毒性肺炎患儿睡眠质量和生命质量的影响

目的:观察重组人干扰素α-1b联合布地奈德雾化对小儿呼吸道合胞病毒性肺炎患儿生命质量和睡眠质量的影响。方法:选取2022年3月至2023年10月福建省莆田市第一医院儿科收治的合胞病毒性肺炎患儿90例作为研究对象,按照随机数字表法分为对照组和观察组,每组45例。对照组予以常规方案用药治疗,观察组予以重组人干扰素α-1b联合布地奈德雾化治疗。比较2组患儿睡眠质量、生命质量以及症状改善时间、炎症介质水平变化。结果:治疗后观察组夜间觉醒次数低于对照组,日平均睡眠时间、夜间最长连续睡眠时间均长于对照组(均P<0.05)。观察组咳嗽、咽喉疼痛、胸闷以及发热症状改善时间均短于对照组(均P<0.05)。治疗后2组患儿的世界卫生组织生存质量测定量表简表(WHOQOL-BREF)评分均高于本组治疗前(均P<0.05),且观察组治疗后的评分高于对照组(P<0.05)。治疗后2组患儿炎症介质白细胞介素-6(IL-6)、C反应蛋白(CRP)、肿瘤坏死因子-α(TNF-α)水平均较本组治疗前降低(均P<0.05),且观察组治疗后各指标水平均低于对照组(均P<0.05)。结论:重组人干扰素α-1b联合布地奈德雾化治疗可以迅速改善合胞病毒性肺炎患儿的临床症状,提升患儿睡眠质量和生命质量。

某地区冬季上呼吸道病毒感染情况分析

目的:收集388例冬季就诊患者上呼吸道病毒核酸样本进行检测分析,为该地区冬季呼吸道疾病临床诊疗提供理论支持。方法:选取2023年12月-2024年2月于山东省某三甲医院就诊的呼吸道感染患者,分别采集口咽拭子标本并采用实时荧光定量PCR法对6种上呼吸道病毒(呼吸道合胞病毒、腺病毒、人偏肺病毒、副流感病毒Ⅰ/Ⅱ/Ⅲ型)进行检测,分析患者感染情况。结果:388例患者中,确诊病毒感染199例(51.29%),其中单一病毒感染143例(36.86%),以呼吸道合胞病毒(RSV)为主;两种以上病毒感染56例(14.44%),以呼吸道合胞病毒(RSV)、腺病毒(Radv)、副流感病毒(PIV)感染为主。在感染人群中,0~5岁儿童病毒感染较其他年龄分组更高,差异有统计学意义(P<0.001)。结论:该地区冬季因呼吸道疾病就诊患者病原体感染以RSV为主,其中病毒感染高发于婴幼儿。儿科及疾病感染科应加强对重点人群的关注并加强病毒感染防护措施,防止患者之间的交叉感染,做到早发现、早诊断、早治疗,减少院内病区呼吸道病毒的流行。

定喘口服液联合重组人干扰素α-1b雾化吸入治疗小儿呼吸道合胞病毒感染患者临床研究

目的探讨小儿呼吸道合胞病毒(RSV)感染患者实施定喘口服液联合重组人干扰素α-1b雾化吸入治疗的应用价值。方法选取2023年3—5月陇南市第一人民医院接诊的RSV感染患者80例,根据随机数字表法将其分为对照组(常规治疗,n=40)、观察组(常规治疗+定喘口服液联合重组人干扰素α-1b雾化吸入治疗,n=40)两组。比较两组治疗后的临床症状消失时间(咳嗽减轻时间、喘憋消失时间、体温复常时间)、治疗前后的生理指标(血氧饱和度、氧合指数)。结果观察组治疗后临床症状消失时间和生理指标水平优于对照组,组间差异均有统计学意义(P<0.05)。结论定喘口服液联合重组人干扰素α-1b雾化吸入治疗小儿呼吸道合胞病毒感染可有效改善患者临床症状和呼吸功能。

表达呼吸道合胞病毒融合前F蛋白的重组人5型腺病毒的构建

目的筛选并构建成功表达A亚型人呼吸道合胞病毒(Human Respiratory Syncytial Virus,HRSV)融合前构象F蛋白的重组人5型腺病毒(Recombinant Human type5 adenovirus,rHADV-5),为制备和研发HRSV重组腺病毒载体疫苗奠定基础。方法在真核表达载体pcDNA3.1(+)上插入具有不同突变位点的HRSV F蛋白编码序列,利用融合前F蛋白单克隆抗体AM14和D25筛选HRSV F蛋白突变体;通过同源重组将筛选出的前构象F蛋白突变体编码序列插入非复制型人5型腺病毒载体,在HEK293细胞中进行重组病毒的包装和扩增,经氯化铯密度梯度法获得纯化的重组病毒;应用夹心ELISA法和Western blot鉴定F蛋白的表达及构象。结果通过AM14和D25单克隆抗体筛选出了2个稳定维持在融和前构象的HRSV F蛋白序列(SC-3M和SC-5M)。将SC-3M和SC-5M编码序列插入非复制型人5型腺病毒载体,对两种重组人5型腺病毒(pAd5-SC-3M和pAd5-SC-5M)和空载体(pAd5-vector)纯化,病毒滴度分别达到2.016×10^(10),2.52×10^(10)和2.948×10^(11)IU/mL。pAd5-SC-3M和pAd5-SC-5M感染HEK293后均能高效表达HRSV融合前构象的F蛋白并维持三聚体结构,且pAd5-SC-5M感染细胞中F蛋白表达量高于pAd5-SC-3M。结论成功在体外传代细胞中获得可高效表达A型HRSV融合前F蛋白的重组人5型腺病毒,为进一步通过动物试验评价该HRSV重组腺病毒载体疫苗奠定了基础。

连花清瘟颗粒联合重组人干扰素α1b雾化吸入治疗小儿呼吸道合胞病毒感染的疗效分析

目的分析小儿呼吸道合胞病毒感染予以雾化吸入重组人干扰素α1b与连花清瘟颗粒联合治疗的临床效果。方法方便选择2018年1月—2020年12月在厦门市第五医院儿科收入院诊治的876例呼吸道合胞病毒感染患儿为研究对象,根据随机对照法分组,分为研究1组(n=438)、研究2组(n=438),研究1组予以雾化吸入重组人干扰素α1b与连花清瘟颗粒联合治疗,研究2组予以雾化吸入重组人干扰素α1b,两组的治疗周期均为1周,分析两组临床症状消失时间、血清炎性因子指标变化。结果研究1组的咳嗽消失、流涕消失、鼻塞消失、退热时间分别为(3.0±1.1)、(2.2±0.5)、(2.9±0.4)、(1.4±0.6)d显著短于研究2组的(4.5±1.8)、(3.6±1.2)、(4.6±1.0)、(3.9±1.8)d,差异有统计学意义(t=14.882、22.538、33.034、27.576,P<0.05);治疗后,研究1组的干扰素-γ(IFN-γ)、白细胞介素-12(IL-12)、白细胞介素-10(IL-10)、白细胞介素-4(IL-4)指标均显著优于研究2组,差异有统计学意义(P<0.05)。结论小儿呼吸道合胞病毒感染予以雾化吸入重组人干扰素α1b与连花清瘟颗粒联用,可显著改善机体炎性因子指标,临床效果明确,值得临床推荐应用。

人呼吸道合胞病毒疫苗研发的突破及挑战

人呼吸道合胞病毒(human respiratory syncytial virus,RSV)已被发现60余年。在经历了20世纪60年代RSV疫苗研发失败后,基于融合前融合糖蛋白(prefusion fusion glycoprotein,preF)的RSV结构性疫苗目前已取得突破性进展,通过接种孕妇和60岁以上老年人群,为新生儿及老年人群提供有效保护,从而解决了预防RSV感染“无苗可用”的历史难题。2023年是RSV疫苗研发的里程碑,也将成为新的起点。在此背景下,本文系统介绍了RSV疫苗研发进展、面临的挑战及今后的发展方向,提出针对RSV不同易感人群应采用不同疫苗形式的科学依据及对策,并对RSV感染重点人群(如血清学阴性婴幼儿等低龄儿童)的疫苗研发难点及候选疫苗形式进行了全面分析。结合基于RNA病毒反向遗传学技术的RSV减毒活疫苗(live-attenuated vaccine,LAV)研发设计、临床试验数据及黏膜疫苗优势,笔者认为RSV LAV是预防6个月及以上婴幼儿和低龄儿童RSV感染的前景较好的候选疫苗,有望为RSV疫苗研发带来新突破。此外,本文就如何加强我国RSV疫苗研发提出建议。

重组人干扰素α-2 a雾化吸入联合盐酸氨溴索治疗呼吸道合胞病毒感染所致支气管肺炎患儿的效果

目的:观察重组人干扰素α-2a雾化吸入联合盐酸氨溴索治疗呼吸道合胞病毒(RSV)感染所致支气管肺炎患儿的效果。方法:选取2020年1月至2023年2月该院收治的120例RSV感染所致支气管肺炎患儿进行前瞻性研究,按照随机数字表法将其分为对照组和研究组各60例。对照组口服盐酸氨溴索片治疗,研究组在对照组基础上联合重组人干扰素α-2a雾化吸入治疗。比较两组临床疗效,治疗前后凝血功能指标[血小板计数(PLT)、D-二聚体(D-D)]水平、血清炎性因子[降钙素原(PCT)、C反应蛋白(CRP)]水平,临床症状消失时间,以及不良反应发生率。结果:研究组治疗总有效率为90.00%(54/60),高于对照组的75.00%(45/60),差异有统计学意义(P<0.05);治疗后,两组血清PLT、D-D水平均低于治疗前,且研究组低于对照组,差异有统计学意义(P<0.05);治疗后,两组血清CRP、PCT水平均低于治疗前,且研究组低于对照组,差异有统计学意义(P<0.05);研究组咳嗽消失时间和退热时间均短于对照组,差异有统计学意义(P<0.05);两组治疗期间均未见明显药物不良反应。结论:重组人干扰素α-2a雾化吸入联合盐酸氨溴索治疗RSV感染所致支气管肺炎患儿可提高治疗总有效率,加快临床症状消失,改善凝血功能,降低炎性因子水平,效果优于单纯盐酸氨溴索治疗。