Effects of ulinastatin combined with thymopentin on cellular immunity, humoral immunity and stress response in severe pneumonia

Objective:To explore the effects of ulinastatin combined with thymopentin on cellular immunity, humoral immunity and stress response in severe pneumonia.Methods: A total of 102 cases of severe pneumonia treated in our hospital from February 2016 to November 2017 were collected as subjects and randomly divided into the control group (n=51) and the observation group (n=51), the two groups were treated with routine symptomatic treatment. The control group was treated with the ulinastatin on the basis of routine treatment, the observation group was treated with thymopentin on the basis of the control group. The changes of cellular immunity, humoral immunity, stress response and liver function in the two groups were compared.Results: Before treatment, there was no significant difference in the levels of CD4+, CD8+, CD4+/CD8+, IgA, IgM, IgG, SOD, MDA, T-AOC, AKP, TB and ALT between the two groups (P>0.05). After treatment, the two groups of CD4+ and CD4+ /CD8+ were significantly increased (P<0.05), CD8+ was significantly lower than before treatment (P<0.05), and CD4+ and CD4+ /CD8+ in the observation group were significantly increased compared with the control group (P<0.05), CD8+was significantly lower than the control group (P<0.05);the two groups of IgA, IgM and IgG were significantly increased compared with those before treatment (P<0.05), and the IgA, IgM and IgG in the observation group were significantly higher than those in the control group (P<0.05);two groups of SOD and T-AOC were significantly higher than before treatment (P<0.05), while MDA was significantly lower than before treatment (P<0.05), and SOD and T-AOC in the observation group were significantly increased (P<0.05), and MDA was significantly lower than that of the control group (P<0.05);two groups of AKP, TB and ALT were significantly lower than those before treatment (P<0.05), and the AKP, TB and ALT in the observation group were significantly lower than those in the control group (P<0.05).Conclusions: ulinastatin combined with thymopentin in patients with severe pneumonia can effectively enhance the cellular immunity and humoral immune function, reduce oxidative stress damage and protect the liver function, which has clinical significance.

Inflammatory factors, cellular immunity and humoral immunity in patients with secretory otitis media

Objective:To investigate the changes of inflammatory factors, cellular immunity and humoral immunity in patients with secretory otitis media.Methods:A total of 82 cases of secretory otitis media admitted in our hospital from January 2017 to December 2017 were selected as the observation group, and 80 healthy volunteers in our hospital were selected as the control group. The tumor necrosis factor-α (TNF-α), calcitonin (PCT), platelet activating factor (PAF), endothelin-1 (ET-1), CD3+, CD4+, CD8+, CD4+/CD8+, IgA, IgG, IgM. were detected and compared.Results: The levels of TNF-α, PCT, PAF and ET-1 in the observation group were (2.21 ± 0.13) ng/mL, (3.96 ± 0.81) ng/mL, (149.50 ± 21.08) ng/mL, and (1.67 ± 0.53) μg/L, which were all higher than those of the control group, the differences were significant. The levels of CD3+, CD4+ and CD4+/CD8+ in the observation group were (51.95 ± 4.47)%, (37.04 ± 3.94)% and (1.10 ± 0.04) respectively, which were all lower than those in the control group, the differences were significant. The level of CD8+ in the observation group was (33.63 ± 3.94)%, higher than that in the control group, the difference was significant. The levels of IgA, IgG and IgM in the observation group were (4.97 ± 0.22) g/L, (31.16 ± 2.53) g/L and (5.12 ± 0.17) g/L respectively, which were all higher than the control group, the differences were significant.Conclusion:Inflammatory factors and immune status of patients with secretory otitis media are abnormal. It is suggested to strengthen clinical monitoring of relevant indicators.

Humoral and cellular immunity against diverse SARS-CoV-2 variants

Since the outbreak of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in late 2019, the virus has rapidly spread worldwide. This has led to an unprecedented global pandemic, marked by millions of COVID-19 cases and a significant number of fatalities. Over a relatively short period, several different vaccine platforms are developed and deployed for use globally to curb the pandemic. However, the genome of SARS-CoV-2 continuously undergoes mutation and/or recombination, resulting in the emergence of several variants of concern (VOC). These VOCs can elevate viral transmission and evade the neutralizing antibodies induced by vaccines, leading to reinfections. Understanding the impact of the SARS-CoV-2 genomic mutation on viral pathogenesis and immune escape is crucial for assessing the threat of new variants to public health. This review focuses on the emergence and pathogenesis of VOC, with particular emphasis on their evasion of neutralizing antibodies. Furthermore, the memory B cell, CD4+, and CD8+ T cell memory induced by different COVID-19 vaccines or infections are discussed, along with how these cells recognize VOC. This review summarizes the current knowledge on adaptive immunology regarding SARS-CoV-2 infection and vaccines. Such knowledge may also be applied to vaccine design for other pathogens.

Impairment of cellular and humoral immunity in overweight Mongolian gerbils (Meriones unguiculatus)

Animal immunity is usually impaired in obesity.We know little about the effect of being overweight or obese on the immune function of wild rodents.The present study is aimed to test the hypothesis that immunity is suppressed in overweight Mongolian gerbils(Meriones unguiculatus).In the study,16 overweight(body mass:90.8-127.6 g)and 16 lean gerbils(body mass:60.5-77.7 g)were randomly selected from a total of 174 male gerbils(body mass range:55.8-144.7 g).Half of the overweight and lean males were injected with sterile saline;the others were immunochallenged(IC)with phytohaemagglutinin and keyhole limpet hemocyanin to assess cellular and humoral immunity,respectively.Body fat mass,wet and dry spleen mass,leukocyte counts,blood glucose levels and serum leptin levels were significantly higher in the overweight gerbils than in the lean gerbils.However,phytohemagglutinin response indicative of cellular immunity and immunoglobulin G concentrations was significantly lower in the IC overweight gerbils than in the IC lean gerbils.These results indicate that cellular and humoral immunity are impaired in the overweight gerbils.Excessive body fat mass,higher leukocyte counts and serum leptin levels imply that overweight gerbils are in a low grade inflammatory state.

Role of autoimmunity in primary biliary cirrhosis

Primary biliary cirrhosis(PBC) is an autoimmune liver disease characterized by the presence of serum autoantibodies and chronic nonsuppurative destructive cholangitis.The pathogenesis of PBC involves environmental factors,genetic predisposition and loss of immune tolerance.In recent years,it has become univocally accepted that an inappropriately activated immune response is one of the most important factors in PBC.In this study,the role of autoimmunity in PBC is summarized and a feasible research orientation is recommended.

Effect of Different Oligosaccharides on Immunity and Production Performance of Piglets

[ Objective] To study the effects of different oligosaccharides on immunity and production performance of piglets.[ Method] A total of 75 Yorkshire x Rongchang piglets were assigned into five groups, 15 in each group. Isomalto-oligosaccharide （ IMO）, fructo-oligosaccharide （ FOS）, mannan-oligosacchadde （MOS）, and mixed oligosacchadde were supplemented to basal diet （7.5 g/kg）, respectively. The control group was also set. The experimental period lasted for 53 d. The clinic symptoms and diarrhea were observed. All piglets were weighed once a week. Feed intake was also recorded. Blood was collected via precaval vein for determination of immunology indexes at the age of 30 and 60 d, respectively. [ Result] The IMO and FOS enhanced cellular immunity of 30-day-old piglets significantly （P 〈 0.05）, and the IMO also enhanced their humoral immunity. The MOS enhanced cellular immunity and humoral immunity of 60-day-old piglets significantly （P 〈 0.05）. It also improved production performance largest, and its diarrhea rate was the lowest. [ Conclusion] Different oligosaccharides have various effects on immunity and production performance of oiolets.

Effects of NS Series Composite Lactobacillus Prepa-ration on Performance,Plasma Biochemical Indexes and Immunity of Sows

[Objective] The study was aimed to investigate the effects of NS series composite lactobacillus preparation on production performance and some immune indexes of sows. [Method] The sows were fed on the diets supplemented with the NS series composite lactobacillus prepara- tion, and the changes of production performance, plasma biochemical indexes, levels of IgG, IgA and IgM in serum and colostrum, and T lympho- cyte subpopulations were detected. [ Result] When the NS series composite lactobacillus preparation was supplemented to the sow diet at a propor- tion of 0.2%, the average weaning litter weight at 21 days old was significantly increased. The serum contents of total protein and glucose as well as the serum activities of aspartate aminotransferase （AST）, alkaline phosphatase （ALP） and superoxide dismutase （SOD） were significantly in- creased after 30 d post delivery. Moreover, the levels of IgG, IgA and IgM in serum and colostrum of sows were significantly increased at the time of delivery and after 30 d post delivery. The antibodies in colostrum could be maintained at high levels. The percentage of CD3 ＊ and CD4~ ｜ympho- cyte subpopulations was also increased after supplementation with the NS series composite lactobacillus preparation at a proportion of 0.2%. [ （Con- des＇ion] The NS series composite lactobacillus preparation can improve performance, promote growth and metabolism, and enhance humoral and cellular immunity in sows.

Functional identification of C-type lectin in the diamondback moth,Plutella xylostella(L.)innate immunity

C-type lectins(CTLs)are a superfamily of Ca^(2+)-dependent carbohydrate-recognition proteins,and an important pattern recognition receptor(PRR)in insect innate immunity which can mediate humoral and cellular immunity in insects.In this study,we report a novel dual carbohydrate-recognition domain(CRD)CTL from Plutella xylostella which we designate PxIML.PxIML is a protein with a 969 bp open reading frame(ORF)encoding 322 amino acids,containing a signal peptide and a dual-CRD with EPN(Glu_(124)-Pro_(125)-Asn_(126))and QPD(Gln_(274)-Pro_(275)-Asp_(276))motifs.The expression of PxIML mRNA in the fat body was significantly higher than in hemocytes and midgut.The relative expression levels of PxIML in the whole insect and the fat body were significantly inhibited after infection with Bacillus thuringiensis 8010(Bt8010)at 18 h,while they were significantly upregulated after infection with Serratia marcescens IAE6 or Pichia pastoris.The recombinant PxIML(rPxIML)protein could bind to the tested pathogen-associated molecular patterns(PAMPs),and the bacteria of Enterobacter sp.IAE5,S.marcescens IAE6,Staphylococcus aureus,Escherichia coli BL21,and Bt8010 in a Ca^(2+)-dependent manner,however,it showed limited binding to the fungus,P.pastoris.The rPxIML exhibited strong activity in the presence of Ca^(2+) to agglutinate Bt8010,Enterobacter sp.IAE5 and S.aureus,but it only weakly agglutinated with E.coli BL21,and could not agglutinate with S.marcescens IAE6 or P.pastoris.Furthermore,the rPxIML could bind to hemocytes,promote the adsorption of hemocytes to beads,and enhance the phenoloxidase(PO)activity and melanization of P.xylostella.Our results suggest that PxIML plays an important role in pathogen recognition and in mediating subsequent humoral and cellular immunity of P.xylostella.

THE HUMORAL AND CELLULAR IMMUNE RESPONSES INDUCED BY HPV18L1-E6/E7 DNA VACCINES IN MICE

Objective To construct eukaryotic expression vector of HPV18 L1-E6, E7 chimeric gene and examine the humoral and cellular immune responses induced by this DNA vaccines in mice. Methods The C-terminal of major capsid protein L1 gene and mutant zinc finger domains of early E6/7 oncogenes in HPV18 were integrated and inserted into eukaryotic expression vector pVAX1 to generate vaccines pVAX1-L1E6Mxx, E7Mxx. CHO cells were transiently transfected with the individual construct. Target protein expressions in the lysate of the transfected cells were measured by ELISA and immunocytochemistry. After BALB/c mice were vaccinated with various recombinant plasmids(pVAX1-L1-E6M3 or pVAX1-L1-E7M3) and immunie adjuvants (pLXHDmB7-2 or LTB) through different administration routes (intramuscular or intranasal) , the great cellular immune responses were produced as revealed by delayed-type hypersensitivity (DTH) and lymphocyte proliferation, and the expression of IL-4 and IFN-γ cells in CD4 + and CD8 + subpopulations. Results The highly efficient expression of pVAX1-L1E6Mxx, E7Mxx vector in host eukaryotic cells were demonstrated both by ELISA and immunocytochemistry. The level of specific serum IgG against HPV in experiment groups mice was much higher than that of control group, and intranuscular immunization group had the highest antibody level. Intramuscular immunization groups were superior to intranasal immunization groups in DTH response, splenocyte proliferation and CD8+ IFN-γ + cells number, but CD4 + IL4 + cell number was higher in intranasal immunization groups. The immunization groups using pLXHDmB7-2 as adjuvant were superior to other groups in immunoresponse. Conclusion These DNA vaccines produce remarkable cellular and humoral immune responses in the mouse and may provide as prophylatic and therapeutic candidates for HPV induced cancer treatment.

Efficient Humoral and Cellular Immune Responses Induced by a Chimeric Virus-like Particle Displaying the Epitope of EV71 without Adjuvant

Objective To eliminate the side effects of aluminum adjuvant and His-tag,we constructed chimeric VLPs displaying the epitope of EV71（SP70） without His-tagged.Then evaluating whether the VLPs could efficiently evoke not only humoral but also cellular immune responses against EV71 without adjuvant.Methods The fusion protein was constructed by inserting SP70 into the MIR of truncated HBc Ag sequence,expressed in E.Coli,and purified through ion exchange chromatography and density gradient centrifugation.Mice were immunized with the VLPs and sera were collected afterwards.The specific antibody titers,Ig G subtypes and neutralizing efficacy were detected by ELISA,neutralization assay,and EV71 lethal challenge.IFN-γ and IL-4 secreted by splenocytes were tested by ELISPOT assay.Results HBc-SP70 proteins can self-assemble into empty VLPs.After immunization with HBc-SP70 VLPs,the detectable anti-EV71 antibodies were effective in neutralizing EV71 and protected newborn mice from EV71 lethal challenge.There was no significant difference for the immune efficacy whether the aluminum adjuvant was added or not.The specific Ig G subtypes were mainly IgG1 and IgG2 b and splenocytes from the mice immunized produced high levels of IFN-γ and IL-4.Conclusion The fusion proteins without His-tagged was expressed and purified as soluble chimeric HBc-SP70 VLPs without renaturation.In the absence of adjuvant,they were efficient to elicit high levels of Th1/Th2 mixed immune response as well as assisted by aluminum adjuvant.Furthermore,the chimeric VLPs have potential to prevent HBV and EV71 infection simultaneously.

Features of Cellular,Humoral and Activation Markers of Immune System and Biophysical Parameters of Superficial Membranes of Lymphocytes of Periphery Blood at Patients with a Breast Cancer

Studied features of cellular and humoral factors of immune system and activation markers of lymphocytes at breast cancer patients.Analyzed biophysical parameters of lymphocyte superficial membranes of periphery blood of breast cancer patients.Features of immune system reaction were:expressed Т - cellular immunodeficiency,deficiency of CD4+Т-helpers/inducers against raised expression of СD8+Т-lymphocyte,suppression of immunoregulatory index,imbalance of immunity humoral link,activity of expression CD16 + and CD56 + on natural killers and rising of expression CD38 + and CD95 + on lymphocytes.Studying of biophysical parameters of lymphocytes superficial membranes has allowed to reveal statistically significant changes characterized by intensifying of electric field and rising ofmicroviscosity,obviously leading to disappearance or weakening of intercellular interactions.

植物乳杆菌CCFM8661增强小鼠免疫力的功能评价

为了通过动物实验评价植物乳杆菌(Lactiplantibacillus plantarum)CCFM8661的免疫调节功能,作者采用120只雄性BALB/c小鼠,分别灌胃植物乳杆菌CCFM8661(低、中、高3个剂量)或安慰剂30 d。之后采用以下方法综合评估植物乳杆菌CCFM8661调节小鼠免疫力的功效:小鼠脾淋巴细胞转化实验及迟发型变态反应(delayed type hypersensitivity,DTH)实验评价小鼠细胞免疫功能;血清溶血素生成实验及抗体生成细胞检测实验评价小鼠体液免疫功能;碳廓清实验及腹腔巨噬细胞吞噬荧光微球实验评价小鼠单核-巨噬细胞功能;自然杀伤(nature-killer,NK)细胞活性检测评估小鼠NK细胞功能。结果显示,植物乳杆菌CCFM8661可明显增强小鼠迟发型变态反应的耳肿胀程度、提升小鼠脾淋巴细胞的增殖水平、促进小鼠血清溶血素的生成、提高小鼠腹腔巨噬细胞的吞噬能力及机体碳处理能力。研究结果表明植物乳杆菌CCFM8661具有增强小鼠免疫力的作用,为其实际应用提供理论依据。

小儿难治性支原体肺炎患儿免疫学水平对预后的影响

目的探讨小儿难治性支原体肺炎患儿免疫学水平对预后的影响。方法回顾性选择2021年6月至2022年4月福建省龙岩市第二医院收治的57例小儿难治性支原体肺炎患儿为研究对象,根据治疗预后分为预后良好组(n=46)和预后差组(n=11)。比较两组细胞免疫、体液免疫、白细胞计数(WBC)、C反应蛋白(CRP)水平,采用多因素logistic回归分析小儿难治性支原体肺炎患儿免疫学水平对预后的影响。结果预后良好组CD4^(+)、CD4^(+)/CD8^(+)均高于预后差组,CD8^(+)、免疫球蛋白(Ig)G、IgE、IgA、WBC和CRP均低于预后差组,差异有统计学意义(P<0.05);多因素logistic回归分析结果显示,CD4^(+)(OR=3.582,95%CI=2.482~6.313)、CD4^(+)/CD8^(+)(OR=6.413,95%CI=5.682~8.452)、CD8^(+)(OR=4.083,95%CI=3.235~4.572)、IgG(OR=1.034,95%CI=0.283~4.394)、IgE(OR=1.593,95%CI=1.241~1.786)、IgA(OR=1.246,95%CI=0.987~1.583)、WBC(OR=1.692,95%CI=1.212~1.889)、CRP(OR=1.326,95%CI=1.021~1.984)均为小儿难治性支原体肺炎患儿预后的免疫水平因素(P<0.05)。结论细胞免疫与体液免疫在难治性支原体肺炎患儿中表达异常,能预测患儿治疗预后,可为临床诊疗提供参考依据。

糖尿病患者接种SARS-Cov-2疫苗后的免疫反应:系统评价

目的系统评价糖尿病患者在接种SARS-CoV-2疫苗后的体液和细胞免疫反应。方法检索Web of Science、PubMed、中国知网、万方数据知识服务平台、维普中文科技期刊全文数据库和中国生物医学文献数据库,获取国内外于2019年12月1日至2022年5月12日公开发表的有关糖尿病患者接种SARS-CoV-2疫苗后的体液和细胞免疫反应的观察性研究,经由2名研究者独立筛选文献和提取资料后,采用美国国立卫生研究质量评价工具对纳入文献进行偏倚风险评价,使用描述性统计方法进行汇总分析。结果13篇文献共纳入66651例研究对象,其中5874例(7.9%)患有糖尿病。7篇文献报道了接种第1剂疫苗后糖尿病患者和对照组的免疫反应,其中3篇文献表明,接种1剂SARS-CoV-2疫苗后,糖尿病患者血清抗体水平和阳性率低于对照组;11篇涉及接种2剂SARS-CoV-2疫苗后的免疫反应的文献中,2篇报道了糖尿病患者可产生与对照组相似的抗体反应,9篇报道了糖尿病患者的血清抗体水平、阳性率或细胞免疫反应低于对照组。结论接种SARS-CoV-2疫苗后糖尿病患者和对照组体液和细胞免疫反应均有所增加,但糖尿病患者增加幅度普遍低于对照组。

石斛酒对小鼠免疫功能作用研究

研究石斛酒对小鼠免疫功能的影响。将250只SPF级昆明小鼠随机分为空白对照组,酒基对照组,石斛酒低、中、高剂量组(3.33 mL/kg、6.67 mL/kg、20.00 mL/kg),连续灌胃30 d。采用迟发型变态反应实验和脾淋巴细胞转化实验观察其对小鼠细胞免疫功能的影响;检测抗体生成细胞数和血清溶血素观察其对小鼠体液免疫功能的影响;采用小鼠碳廓清实验和小鼠腹腔巨噬细胞吞噬鸡红细胞实验观察其对小鼠单核-巨噬细胞吞噬功能的影响;采用乳酸脱氢酶(LDH)测定法观察其对小鼠NK细胞活性的影响。结果表明,与空白对照组及酒基对照组比较,中、高剂量能显著提高小鼠NK细胞活性及小鼠迟发型变态反应能力(P<0.05),高剂量能显著提高抗体生成细胞数及半数溶血值(P<0.05),表明石斛酒具有增强免疫力的功能。

肠道微生物对宿主适应性免疫的影响

肠道微生物与宿主共同进化,形成了不可分割的宿主-微生物共生关系。这些共生微生物通过参与适应性免疫的发育和维持,在机体免疫系统中发挥了重要作用。适应性免疫系统通过B细胞介导的体液免疫和T细胞介导的细胞免疫维持机体稳态。肠道微生物可以直接调节B、T细胞的分化和活化,保护机体免遭病原体感染。本文综述肠道微生物对宿主早期免疫系统发育、细胞免疫和体液免疫的调控作用,以期为研究“微生物-宿主互作”对宿主适应性免疫的调控作用提供理论参考。

补脾益肾类中药复方干预重症肌无力的免疫调节机制研究进展

重症肌无力是一种自身免疫性神经系统难治性疾病,补脾益肾中药复方可通过免疫调节作用发挥确切疗效。故通过归纳治疗重症肌无力相关的补脾益肾类中药复方,并从临床试验和基础实验两方面总结研究方案,分析补脾益肾类中药复方治疗重症肌无力的免疫调节机制,包括降低乙酰胆碱受体抗体和免疫球蛋白G浓度等体液免疫机制,维持Th1/Th2、Th17/Treg动态平衡等细胞免疫机制,为后续补脾益肾类中药复方在重症肌无力治疗中的应用及其免疫机制的研究提供参考。

miRNA-126及免疫功能指标对ICU重症肺部感染患者预后的预测价值

目的探究血液与肺泡灌洗液(bronchoalveolar lavage fluid,BALF)中微小RNA-126(miR-126)及免疫功能指标对重症监护病房(intensive care unit,ICU)重症肺部感染患者预后转归的预测价值。方法选取2019年3月至2021年3月锦州医科大学附属第一医院ICU治疗的重症肺部感染患者96例为重症组,并募集同期非重症肺部感染患者88例为非重症组,根据重症组患者28 d预后分为存活组和病死组,比较各组血清与肺泡灌洗液中miR-126水平、细胞免疫指标CD3^(+)、CD4^(+)、CD8^(+)T淋巴细胞比例、体液免疫指标免疫球蛋白(IgG、IgM、IgA)。结果重症组患者血液及BALF中miR-126、外周血CD3^(+)、CD4^(+)/CD8^(+)、血清IgG、IgM水平均低于非重症组,APACHEⅡ评分高于非重症组(P<0.05);Pearson相关分析显示,血液及BALF中miR-126、免疫功能指标CD4^(+)/CD8^(+)水平分别与APACHEⅡ评分呈负相关(r=-0.432、-0.459、-0.538,P<0.05);存活组患者血液及BALF中miR-126、外周血CD3^(+)、CD4^(+)/CD8^(+)、血清IgG水平均高于病死组(P<0.05);受试者工作特征曲线(ROC)显示,血液及BALF中miR-126、免疫功能指标联合预测患者预后曲线下面积(AUC)为0.894,95%CI为0.814~0.947,均高于各单一指标。结论血液与BALF中miR-126、免疫功能指标与重症肺部感染病情密切相关,是预测患者预后的重要指标。

饲料中添加抗菌肽对肉牛免疫机能的影响

[目的]为抗菌肽在兽医临床上的使用剂量和使用方法提供理论参考。[方法]采用随机数字表法将80头6月龄的西门塔尔牛分为4组,每组20头,分别为对照组、抗菌肽低剂量组、中剂量组、高剂量组。在试验第60天采集西门塔尔牛的静脉血,并应用酶标仪检测西门塔尔牛血清中IL-6、IL-10、TNF-α、IgG、IgA和IgM含量。[结果]在试验第60天,与对照组相比,抗菌肽低剂量组、中剂量组和高剂量组西门塔尔牛血清中IL-10含量分别显著提高30.33%、51.36%、60.85%,IgA含量分别显著提高15.94%、36.23%、43.48%;抗菌肽中剂量组、高剂量组西门塔尔牛血清中IgG含量分别显著提高45.03%、51.27%;各组血清中IgM含量无显著差异。[结论]抗菌肽能够一定程度提升肉牛机体的体液免疫和细胞免疫功能。

DNA vaccine prime and replicating vaccinia vaccine boost induce robust humoral and cellular immune responses against MERS-CoV in mice

As of December 2022,2603 laboratory-identified Middle East respiratory syndrome coronavirus(MERS-CoV)infections and 935 associated deaths,with a mortality rate of 36%,had been reported to the World Health Organization(WHO).However,there are still no vaccines for MERS-CoV,which makes the prevention and control of MERS-CoV difficult.In this study,we generated two DNA vaccine candidates by integrating MERS-CoV Spike(S)gene into a replicating Vaccinia Tian Tan(VTT)vector.Compared to homologous immunization with either vaccine,mice immunized with DNA vaccine prime and VTT vaccine boost exhibited much stronger and durable humoral and cellular immune responses.The immunized mice produced robust binding antibodies and broad neutralizing antibodies against the EMC2012,England1 and KNIH strains of MERS-CoV.Prime-Boost immunization also induced strong MERS-S specific T cells responses,with high memory and poly-functional(CD107a-IFN-γ-TNF-α)effector CD8t T cells.In conclusion,the research demonstrated that DNA-Prime/VTT-Boost strategy could elicit robust and balanced humoral and cellular immune responses against MERS-CoV-S.This study not only provides a promising set of MERS-CoV vaccine candidates,but also proposes a heterologous sequential immunization strategy worthy of further development.