New progress of novel COVID-19 variants and its effect on vaccine immune protection

The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)poses a serious threat to human life and health as well as social and economic development.In order to deal with this public health event,scientific research institutions around the world have rapidly developed and put vaccines into urgent use,bringing hope to the victory over the epidemic.However,as the Novel Coronavirus continues to spread throughout the world,the virus genome has mutated to form a variety of variants.Among them,the Alpha,Beta,Gamma,Delta and Omicron variants show higher infectivity and higher resistance to vaccines and neutralizing antibodies,posing new challenges to the prevention and treatment of COVID-19.At present,the effect of variants on the effectiveness of developed vaccines has become a hot topic of global discussion.In this paper,we briefly review the new progress of novel Coronavirus variants and their effects on vaccine immune protection.

Growth performance,digestive enzyme activities and serum nonspecific immunity of the red tilapia(Oreochromis mossambicus×Oreochromis niloticus)feddiets supplemented with ultrafine powder of Enteromopha prolifera

The present study evaluated ef fects of ultrafine powder of the green macroalgae E nteromopha prolifera as dietary supplement on growth performance, digestive enzyme activities and serum nonspecific immune responses of the red tilapia(O reochromis mossambicus × Oreochromis niloticus). The red tilapia were fed five diets supplemented with different levels of E. prolifera ultrafine powder as well as a control diet containing no E. prolifera for seven weeks(Diets 0–6 contained 0(control), 10, 20, 30, 40 and 50 g/kg of E. prolifera ultrafine powder, respectively). The results showed that diets supplemented with E. prolifera ultrafine powder generally improved growth, immunity and digestive enzyme activities of the red tilapia. In particular, the fish fed the diet incorporated 50 g/kg (5%) E. prolifera ultrafine powder(Diet 5) achieved the highest percentage weight gain, specific growth rate and the condition factor(increased by 15.4%, 8.0% and 5.7%, respectively when compared to the control). Feeding the diet also led to significantly increases( P <0.05) in serum nonspecific immune responses, including total superoxide dismutase, acid phosphatase, alkaline phosphatase, lysozyme activities and serum total protein(increased by 19.4%, 48.1%, 29.5%, 30.3% and 8.7%, respectively) as well as digestive enzyme activities of erepsin, gastric amylase, gastric lipase, pepsin, intestinal amylase and gastric lipase(increased by 15.7%, 33.3%, 16.3%, 21.3%, 52.3% and 28.2%, respectively) than those of the control. Based on these results, it is recommended that the inclusion level of E. prolifera ultrafine powder in the diet of the red tilapia should be 50 g/kg(or 5%).

Persistence of hepatitis B vaccine immune protection and response to hepatitis B booster immunization

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Immune protection of auxiliary liver to other allograft: report of 3 cases

OBJECTIVE: To assess the immune status of auxiliary liver transplantation and to clarify the immune protection of auxiliary liver to other allograft. METHODS: Immunological markers and pathological changes in 3 patients undergoing auxiliary liver transplantation were analysed. RESULTS: The lower the concentration of immunosuppressive agent, the less the rejection and the milder the intensity in the 3 patients. The function of allograft after auxiliary liver transplantation was excellent. CONCLUSIONS: Patients are in a low immune reaction state after auxiliary liver transplantation. Auxiliary liver can protect other allografts by related immunological mechanisms. The side-effects of low-concentration immunosuppressive agents on auxiliary liver and other allografts are mild.

The Mental Protection System for Protective Behaviors: The Social Brain and the Mental Immune System

The physical protection system of the body consists of the protective organs for vulnerable body parts-functions and the protective countermeasures against invaders (pathogens), but to survive, the body also requires the protective social groups for vulnerable social members-functions and the protective instinctive mental countermeasures against adversities such as hardship, danger, and unfamiliarity-uncertainty. As a result, this paper proposes that the mental protection system of the body consists of the social brain to set up the protective social groups for vulnerable social members-functions and the mental immune system to produce the protective mental countermeasures against adversities. This paper proposes that from the social brain, the protective social groups include alliance group for vulnerable individuals, kinship-friendship group for vulnerable children, interdependent specialists group for vulnerable pregnant females, territorial group for social boundary, connective group for social connection, and competitive group for social competition. From the mental immune system, the mental protective countermeasures include comforter against hardship, hyperactivity against danger, phobia against unfamiliarity-uncertainty, and rationality against unfamiliarity-uncertainty. The overactive mental immune system causes mental allergies and auto immune diseases as personality-mental disorders against ubiquitous harmful and harmless perceived adversities, correlating to physical allergies and auto immune diseases against ubiquitous harmful and harmless detected invaders. The mental protection system also produces personality traits, social moralities, social organizations, social systems, religions, and cultures as described in this paper. The mental protective system is the source of protective behaviors.

Efficacy of phytogenic extracts on growth performance and health of tilapia (Oreochromis niloticus × O. aureus)

The present study was conducted to evaluate the efficacy of phytogenic extract on growth and health of tilapia.Three experimental diets were designed as the basal diet(Con)and phytogenic extract(Flourishing,F)supplemented diets at 0.5 and 1 g/kg inclusion(F-1 and F-2),which the phytogenic additive was extracted from Eucommia ulmoides,Astragalus membranaceus,Lonicera japonica and Codonopsis pilosula.The three diets were fed to juvenile tilapia(14.0±0.1 g)with 30 fish per cage,and three replicate cages from the three groups were placed in one indoor concrete pool(a total of three pools were used).After 8 weeks of feeding,the weight gain was significantly increased,and feed conversion ratio was decreased in F-2 group(P<0.05)when compared to the control.Both levels of phytogenic extract significantly promoted the retentions of protein and lipid and the apparent digestibility coefficient of dry matter and protein(P<0.05).The activity of superoxide dismutase and the levels of white blood cells,haemoglobin and glutamic pyruvic transaminase were also significantly increased by the supplementation of phytogenic extract(P<0.05).The villus height in anterior intestine was significantly enhanced in F-1 and F-2 groups(P<0.05).After challenging with Aeromonas hydrophila,the cumulative mortality was significantly declined in F-1 and F-2 groups(P<0.05).In summary,the dietary supplementation of phytogenic extract at 1 g/kg feed could provide positive efficiency on growth,nutrient utilization,immunity,gut morphology and disease resistance of tilapia under the present conditions.

Construction of Salmonella Pullorum ghost by co-expression of lysis gene E and the antimicrobial peptide SMAP29 and evaluation of its immune efficacy in specific-pathogen-free chicks

In this study, a safety enhanced Salmonella Pullorum （S. Pullorum） ghost was constructed using an antimicrobial peptide gene, and evaluated for its potential as a Pullorum disease （PD） vaccine candidate. The antimicrobial peptide SMAP29 was co-expressed with lysis gene E to generate S. Pullorum ghosts. No viable bacteria were detectable either in the fermentation culture after induction of gene E- and SMAP29-mediated lysis for 24 h or in the lyophilized ghost products. Specific-pathogen- free （SPF） chicks were intraperitoneally immunized with ghosts at day 7 of age and no mortality, clinical symptoms or signs of PD such as anorexia, depression and diarrhea were observed. On challenge with a virulent S. Pullorum strain at 4 wk post-immunization, a comparatively higher level of protection was observed in the S. Pullorum ghost immunized chickens with a minimum of pathological lesions and bacterial loads compared to the birds in inactivated vaccine groups. In addition, immunization with the S. Pullorum ghosts induced a potent systemic IgG response and was associated with significantly increased levels of cytokine IFN-y and IL-4 and relative percentages of CD4＋ and CD8＋ T lymphocytes. Our results indicate that SMAP29 can be employed as a new secondary lethal protein to enhance the safety of bacterial ghosts, and to prepare a non-living bacterial vaccine candidate that can prevent PD in chickens.

In vivo anti-tumor effect of hybrid vaccine of dendritic cells and esophageal carcinoma cells on esophageal carcinoma cell line 109 in mice with severe combined immune deficiency

AIM： To develop a fusion vaccine of esophageal carcinoma cells and dendritic cells （DC） and observe its protective and therapeutic effect against esophageal carcinoma cell line 109 （EC109）. METHODS： The fusion vaccine was produced by fusing traditional polyethyleneglycol （PEG）, inducing cytokine, sorting CD34＋ magnetic microbead marker and magnetic cell system （MACS）. The liver, spleen and lung were pathologically tested after injection of the fusion vaccine. To study the therapeutic and protective effect of the fusion vaccine against tumor EC109, mice were divided immune group and therapeutic group. The immune group was divided into P, E, D and ED subgroups, immunized by phosphate buffered solution （PBS）, inactivated EC109, DC and the fusion vaccine respectively, and attacked by EC109 cells. The tumor size, weight, latent period and mouse survival period were recorded and statistically analyzed. The therapeutic group was divided into four subgroups： P, inactivated EC109, D and ED subgroups, which were attacked by EC109 and then treated with PBS, inactivated EC109, DC, and EC109-DC respectively. Pathology and flow cytometry were also used to study the therapeutic effect of the fusion vaccine against EC109 cells.RESULTS： Flow cytometry showed that the expression of folate receptor （FR）, EC109 （C）, Des （D） in human nasopharyngeal carcinoma cell line （HNE1） （B） was 78.21%, 89.50%, and 0.18%, respectively. The fusion cells （C） were highly expressed. No tumor was found in the spleen, lung and liver after injection of the fusion vaccine. Human IgG was tested in peripheral blood lymphocytes （PBL）. In the immune group, the latent period was longer in EC109-DC subgroup than in other subgroups, while the tumor size and weight were also smaller than those in ED subgroup. In the therapeutic group, the tumor size and weight were smaller in ED subgroup than in P, inactivated EC109 and DC subgroups. CONCLUSION： Fusion cells are highly expressed not only in FR but also in CD80. The fusion vaccine has a distinctive protective effect against tumor EC109 and can inhibit the growth of tumor in mice, and its immune protection against tumor attack is more significant.

RADIOIMMUNOTOXICOLOGICAL EFFECT OF ENRICHED URANIUM ON CENTRAL AND PERIPHERAL IMMUNE CELLS AND THE PROTECTIVE ACTION OF IL－1 AND IL－2

Accumulation of enriched 235U-UO2F2 in the body had injurious effects on theimmune function of central and peripheral immune cells. After an intravenousinjection of beaU--UO,F,, the spontaneous ’H--TdR incorporation in thymocytes andbone marrow cells decreased, with the thymocytes damaged more markedly. Theproliferation ability of spleen T and B lymphocytes were both inhibited, with Blymphocytes inhibited more severely. In spleen B lymphocytes the IL-- 1 production andIL--2 consumption were diminished. The inhibition of spleen B lymphocyteproliferation by 'U-- UOZFZ was partially restored by adding exogenous IL-- 1 or IL--2to the cultured lymphocytes obtained from 'U injected mice.

基于免疫调节探讨葛根汤颗粒治疗小鼠病毒性肺炎的作用机制

目的研究葛根汤颗粒对甲型流感病毒(influenza A virus,IAV)致小鼠病毒性肺炎模型的药效评价及免疫调节作用。方法ICR小鼠,13~15 g,分为正常对照组、模型对照组,磷酸奥司他韦阳性药对照组及葛根汤颗粒高、中、低剂量组(6.6、3.3、1.7 g-1·kg^(-1)·d^(-1)),每组10只,采用IAV(FM1株)病毒液感染建立小鼠病毒性肺炎模型,同时给予相关药物治疗。观察各组小鼠肺指数及肺指数抑制率,RT-PCR法检测肺组织核酸,ELISA法检测小鼠肺组织因子白介素-6(IL-6)、白介素-10(IL-10)、肿瘤坏死因子TNF-α;同时采用IAV(FM1株)病毒液滴鼻感染小鼠,造成死亡保护模型,观察小鼠感染后2周内的死亡情况,计算小鼠的死亡率、死亡保护率、平均存活天数和生命延长率。结果葛根汤颗粒中剂量组肺指数及肺组织病毒载量显著降低(P<0.01),肺指数抑制率为50.73%;葛根汤颗粒高、中剂量组肺组织炎性因子IL-10含量显著降低(P<0.01)、葛根汤颗粒中、低剂量组肺组织炎性因子TNF-α含量显著降低(P<0.01);葛根汤颗粒3个剂量组肺组织炎性因子IL-6含量显著降低(P<0.01);模型组小鼠死亡率90%,平均存活天数9.45 d,葛根汤颗粒3个剂量组小鼠死亡率显著降低、平均存活天数显著延长,生命延长率显著提高(P<0.01)。结论葛根汤颗粒可通过调节模型小鼠免疫炎性因子水平达到改善病毒性肺炎小鼠免疫功能的作用,同时可显著降低模型小鼠肺指数和肺组织病毒载量,从而减轻模型小鼠的肺部炎性损伤;对模型小鼠有死亡保护作用。

鸭短喙侏儒综合征亚单位疫苗安全性及免疫效果评价

旨在评价鸭短喙侏儒综合征(SBDS)亚单位疫苗(rBac-JS01 VP2株)的免疫效果。将40只产蛋母鸭和4只成年公鸭随机分成2组,每组产蛋母鸭20只和成年公鸭2只,试验组母鸭经颈背侧皮下注射疫苗0.5 mL,阴性对照组母鸭经颈背侧皮下注射PBS 0.5 mL。免疫后2、4和6个月,分别收集各组种鸭鸭蛋并人工孵化,每个阶段任意选择1日龄健康的公、母雏鸭各20只进行SBDS-JS01毒株攻毒,记录攻毒后雏鸭体重和发病情况,并在攻毒后第3、5、7、14、21天采集雏鸭肛拭子检测排毒情况,每组随机剖检2只雏鸭,观察组织病理变化,PCR检测各组病毒分布情况;免疫后2、4、6个月,采集产蛋鸭血液并分离血清,收集鸭蛋并提取、纯化卵黄抗体,采用SBDS-JS01株测定病毒中和抗体效价。结果显示:种鸭免疫后2、4、6个月,所孵雏鸭对SBDS-JS01攻毒保护率分别为100%、95%、90%,观察期各时间段内免疫攻毒组与对照组相比,试验鸭的体重无显著性差异(P>0.05),而非免疫攻毒组试验鸭的体重极显著低于其他各组(P<0.01);雏鸭攻毒后,免疫攻毒组在免疫后2个月所孵雏鸭肛拭子检测均呈阴性,观察期内各时间段组织器官病毒分布均低于非免疫攻毒组;疫苗免疫组在免疫后2、4、6个月血清的SBDSJS01中和抗体效价分别为(10.51±1.59)log_(2)、(9.46±1.27)log_(2)、(8.83±1.15)log_(2),卵黄中和抗体效价分别为(10.12±1.46)log_(2)、(9.37±1.06)log_(2)、(8.49±1.21)log_(2);不同时期的血清中和抗体效价和卵黄中和抗体效价基本一致,升降趋势相同,且与被动免疫攻毒保护水平变化具有很好的相关性。提示:制备的SBDS亚单位疫苗安全性高,免疫效果较好,对SBDS病毒可提供持续有效的保护力。

右美托咪定对老年腹腔镜结肠癌根治术患者免疫保护及血微循环转移影响的临床观察

目的探讨右美托咪定对老年腹腔镜结肠癌根治术患者免疫保护及血微循环转移的影响。方法选取2021年6月至2023年6月在上海市第七人民医院78例行腹腔镜结肠癌根治术患者为研究对象,随机分为2组,其中试验组(n=39)于麻醉诱导前采用右美托咪定复合喷他佐辛,对照组(n=39)采用等速率等量生理盐水以及喷他佐辛。比较两组围麻醉期指标,分别于麻醉诱导前(T_(0))、手术结束即刻(T_(1))、术后30 min(T_(2))、术后6 h(T_(3))比较患者血流动力学指标变化,于麻醉诱导前(T_(0))、术后6 h(T_(3))、24 h(T_(4))、48 h(T_(5))对患者免疫功能及血微循环转移进行评估,并比较两组术后不良反应发生率。结果试验组呛咳评分为(2.02±0.36)分、对照组呛咳评分为(2.61±0.49)分;试验组躁动评分为(1.66±0.21)分、对照组躁动评分为(2.07±0.35)分;差异具有统计学意义(P<0.05)。两组患者T_(0)时刻HR、SpO2及MAP比较差异无统计学意义P>0.05),T_(2)时刻实验组HR显著低于对照组(76.38±7.33 vs.95.64±9.32),差异具有统计学意义(P<0.05);T_(1)、T_(2)时刻试验组MAP显著低于对照组(73.84±7.94 vs.106.85±10.37,80.37±8.39 vs.102.84±9.38),差异具有统计学意义(P<0.05)。T_(3)~T_(5)时间点,两组CD3^(+)、CD4^(+)及CD4^(+)/CD8^(+)均低于T_(0),试验组各指标均低于对照组,差异有统计学意义(P<0.05)。T_(0)时刻,两组CK19、CK20阳性率比较无差异(P>0.05);T_(3)~T_(5),试验组CK19、CK20阳性率均低于对照组,差异具有统计学意义(P<0.05)。对照组、试验组不良反应发生率分别为15.4%和10.4%。结论右美托咪定可优化老年腹腔镜结肠癌根治术围麻醉期指标,有效减轻免疫抑制,降低血微循环转移风险,且安全性良好,值得临床进一步应用。

雷公藤多苷片对IgA肾病大鼠LIGHT-HVEM/LTβR通路的影响

目的 基于炎症相关通路探讨雷公藤多苷片对IgA肾病大鼠肾脏的作用机制。方法 雄性SPF级SD大鼠,随机分为空白组、造模组。造模组采用联合“牛血清白蛋白+四氯化碳+脂多糖”建立IgA肾病大鼠模型。造模成功的大鼠随机分为模型组、泼尼松组、雷公藤多苷片组,于第13周开始治疗组灌胃给药,给药4周后留取大鼠24 h尿液、血液、肾组织并检测尿红细胞数、24 h-UTP、BUN、Scr;ELISA检测血清IL-1β、TNF-α水平;HE染色观察各组大鼠肾组织病理学变化;Western blot及RT-PCR检测大鼠肾组织LIGHT、HVEM、LTβR蛋白及其mRNA的表达。结果 雷公藤多苷片明显降低IgA肾病大鼠尿红细胞数、24 h-UTP、BUN、Scr水平,改善肾组织病理,降低血清炎症因子IL-1β、TNF-α水平,降低肾组织中LIGHT、HVEM、LTβR蛋白及其mRNA表达水平。结论 雷公藤多苷片可能通过下调LIGHT-HVEM/LTβR信号通路,抑制免疫反应,减少炎症因子释放,从而减轻炎症反应,降低尿红细胞及尿蛋白,改善肾脏病理损伤,保护肾功能。

具有切换特性和免疫控制的计算机病毒传播模型

针对目前计算机病毒传播建模研究中没有综合考虑安全防护以及病毒持续更新的影响,提出具有切换特性和免疫控制的计算机病毒SEIR(Susceptible-Exposed-Infected-Recovery)传播模型。考虑安全防护措施和病毒更新的影响,构建切换型病毒传播模型,该模型由低防护子系统和高防护子系统构成。考虑免疫控制策略,构建切换脉冲型病毒传播模型。为验证模型的有效性,分别在BA无标度网络和SW小世界网络进行数值仿真,并且进行对比分析。实验结果表明:在SW小世界网络中免疫控制策略更能有效控制病毒的传播;低防护传播期与高防护传播期的比值越小,达到平稳时潜伏节点和感染节点的密度越小;病毒的更新周期越长,潜伏节点和感染节点的峰值密度越低。

基于分布式系统的植保机智能与安全性能优化

针对植保机智能化程度和安全性能无法满足要求以及过多的信息资源造成植保机无法进行合理的任务分配问题,基于分布式系统对植保机进行了设计,并对其智能和安全性能进行优化。为了对多植保机进行调度,解决任务分配问题,对植保机的分布式系统软件进行了设计,包括建立植保机的一对多任务分配模型,并对模型进行人工免疫算法设计,以在较短的时间内得到最优的任务分配方式。为了验证植保机的性能,对植保机进行了多任务分配试验和智能变量喷洒试验,结果表明:植保机可根据飞行任务自动调整喷药量,实现智能变量喷洒,且可快速地对植保机进行任务分配。

大口黑鲈鰤鱼诺卡氏菌传代弱毒株特性及免疫效果评价

为探究鰤鱼诺卡氏菌(Nocardia seriolae)强毒株LY20810 F1与其传代弱毒株LY20810 F110的特性差异,比较了两个菌株的生物学特征、毒力基因序列、致病力及引起大口黑鲈免疫反应的差异,并评价了弱毒株LY20810 F110对大口黑鲈的免疫保护效果。结果表明,通过BHI培养基连续传代培养110代次后,菌株LY20810 F110的菌落、菌体形态发生显著变化,其生长速度较原始毒株LY20810 F1快1倍以上。通过比较两株菌的10个毒力基因序列,发现菌株LY20810 F110的SodC和ESAT6基因发生了单位点突变。致病力测试结果显示,强毒株LY20810 F1以0.1 mL 1×10^(7) cfu/mL攻毒剂量感染大口黑鲈,30d内鱼累积死亡率为100%,而传代弱毒株LY20810 F110在相同剂量下未造成鱼死亡。强毒株LY20810 F1攻毒3d后引起脾脏、头肾中IL-1β、IL-10、TNF-α、IFN-γ等炎症细胞因子显著上调,表明细菌感染引起炎症风暴。传代弱毒株LY20810 F110在感染中后期(14d和28d)诱导包括IgM、CD4-α、CD8-α、MHCI-α等8种免疫因子的上调。免疫效果评价结果显示,弱毒株LY20810 F110的注射、浸泡免疫(1×10^(8) cfu/mL)对大口黑鲈的相对保护率分别为75.0%和66.7%,有效降低了鰤鱼诺卡氏菌入侵造成大口黑鲈脾脏和头肾的病理损伤。以上结果表明,鰤鱼诺卡氏菌传代弱毒株LY20810 F110是安全有效的弱毒疫苗候选株,将为诺卡氏菌减毒疫苗的研制提供科学依据。

猪附红细胞体eno基因重组腺病毒疫苗对仔猪免疫效果的研究

为了评价猪附红细胞体eno基因重组腺病毒疫苗(Ad5-M/eno重组腺病毒疫苗)对仔猪的免疫效果,试验将12头仔猪随机分为3组,分别为Ad5-M/eno重组腺病毒疫苗组、重组空载体腺病毒组和PBS对照组,分别于3组仔猪的颈部肌肉注射Ad5-M/eno重组腺病毒疫苗(浓度为1×10^(10)pfu/mL)、空载体重组腺病毒(浓度为1×10^(10)pfu/mL)和PBS各2.5 mL,于试验第0,21天分两次免疫。第2次免疫后第14天,麻醉后手术切除仔猪脾脏,采用密度梯度离心法提取猪脾脏淋巴细胞,利用流式细胞仪检测仔猪CD3^(+)、CD4^(+)和CD8^(+)T淋巴细胞含量。于第1次免疫前(第0天)及免疫后第7,14,21,28,35,42,49天无菌采集各组试验猪的颈静脉血,分离血清,检测每组仔猪抗猪附红细胞体特异性抗体IgG效价及IgG_(1)、IgG_(2a)和细胞因子白细胞介素-4(IL-4)、γ干扰素(IFN-γ)水平,评价Ad5-M/eno重组腺病毒疫苗对仔猪的细胞与体液免疫应答效果。结果表明:Ad5-M/eno重组腺病毒疫苗组的CD3^(+)、CD4^(+)和CD8^(+)T淋巴细胞含量极显著高于重组空载体腺病毒组和PBS对照组(P<0.01),Ad5-M/eno重组腺病毒疫苗组的CD4^(+)/CD8^(+)显著高于重组空载体腺病毒组和PBS对照组(P<0.05),重组空载体腺病毒组和PBS对照组之间的CD3^(+)、CD4^(+)和CD8^(+)T淋巴细胞含量及CD4^(+)/CD8^(+)差异不显著(P>0.05)。免疫后第28,35,42,49天,Ad5-M/eno重组腺病毒疫苗组的抗猪附红细胞体特异性IgG抗体效价及IgG_(1)、IgG_(2a)和细胞因子IL-4和IFN-γ水平极显著高于重组空载体腺病毒组与PBS对照组(P<0.01),重组空载体腺病毒组与PBS对照组之间差异不显著(P>0.05)。说明猪附红细胞体eno基因重组腺病毒疫苗可以诱导仔猪产生强烈的细胞免疫和体液免疫应答。

肠艾美耳球虫重组微线蛋白2对家兔免疫保护效果评价

本研究旨在评价肠艾美耳球虫重组微线蛋白2(rEiMIC2)对兔的免疫保护效果,为肠艾美耳球虫重组亚单位疫苗的研究提供参考。在肠艾美耳球虫转录组数据中筛选出EiMIC2基因,进行克隆、原核表达和蛋白纯化,并采用免疫印迹检测重组蛋白的免疫反应性。将35日龄无球虫新西兰幼兔32只随机分为4组(未免疫未攻虫组、未免疫攻虫组、pET-32a(+)载体组和rEiMIC2免疫组),每组8只,未免疫未攻虫组和未免疫攻虫组每只颈部皮下注射1 mL无菌PBS,pET-32a(+)载体组和rEiMIC2免疫组每只分别接种100μg pET-32a(+)载体蛋白、rEiMIC2,首免后2周进行二免。二免14 d后,除去未免疫未攻虫组,其余3组每只新西兰兔口服接种5×10^(4)个肠艾美耳球虫孢子化卵囊;攻虫14 d后安乐死所有新西兰兔。重组蛋白免疫兔后通过观察临床症状、肠道病变、测定兔的相对增重率、卵囊减少率、抗球虫指数(ACI)值和料肉比以及检测血清中特异性IgG、IL-2、IL-4、IL-10、IFN-γ综合评价rEiMIC2的免疫保护效果。结果显示,EiMIC2基因开放阅读框长度为1 605 bp,编码的蛋白分子质量约为57.68 ku。免疫印迹显示rEiMIC2能够被阳性血清所识别,表明其具有良好的免疫反应性。免疫保护试验显示:攻虫后各组幼兔陆续出现精神沉郁和腹泻的症状,未免疫攻虫组和rEiMIC2免疫组各有1只兔死亡;rEiMIC2免疫组相对增重率为73.97%,卵囊减少率为69.98%,ACI值为136.97,料肉比为3.98∶1,与未免疫攻虫组差异显著(P<0.05);rEiMIC2免疫组肠道病变与未免疫攻虫组相比较轻,血清中特异性IgG水平显著高于未免疫攻虫组(P<0.05)。综上,rEiMIC2免疫兔后,能有效减少卵囊排出和增重损失,减轻肠道损伤,具有一定的保护效果。

疫苗的结构基础和分子设计

[背景]结构疫苗学方法是逆向疫苗学的逻辑演进,其核心是利用保护性决定因子来有选择地设计抗原,进而重新设计和简化,以纳入疫苗组合中.该技术旨在开发创新性传染病疫苗和设计具有广谱保护的疫苗免疫原,尤其对于目前仍无疫苗能用于防控的艾滋病毒(HIV)、寨卡病毒、结核杆菌及多种耐药菌引发的严重威胁人类健康的传染病具有重大应用前景.[进展]目前重大传染病疫苗的研发困难主要集中在病原体抗原表位的变异性,然而随着利用结构生物学疫苗设计的初步成功,结构疫苗学技术在疫苗研发陷入困境的情况下展现出巨大的应用潜力.许多重要病原体如HIV、新型冠状病毒、流感病毒的抗体-抗原复合物结构得到解析,许多有潜力的候选抗原表位陆续被发现.本文主要介绍疫苗的结构基础和如何基于结构进行理性分子设计.[展望]如何将这些表位应用于抗原改造,设计出保护性集中的免疫原或疫苗是结构疫苗学下一步需要努力的目标.结构疫苗学结合现代计算和人工智能技术的应用,可为21世纪的医学和科技挑战提供前所未有的解决方案,疫苗研发领域有望实现重大飞跃.

利用大蜡螟幼虫和小鼠感染模型筛选猪链球菌血清2、3和9型三价灭活疫苗候选菌株

旨在评估临床分离的猪链球菌血清2、3、9型强毒株制备的三价灭活疫苗对小鼠的免疫保护效果。使用大蜡螟幼虫感染模型和小鼠感染模型,从临床分离的猪链球菌中筛选出血清2、3和9型强毒株各1株(SS1803、SS1803024、SS1696),检测其生长曲线和毒力因子。将菌株分别灭活及混合灭活后与佐剂混合,用4×10^(7)CFU、8×10^(7)CFU SS1803、2×10^(8)CFU、5×10^(8)CFU SS1803024、1×10^(8)CFU、5×10^(8)CFU SS1696及三价灭活苗(2×10^(7)CFU SS1803^(+)1.5×10^(8)CFU SS1803024^(+)3×10^(7)CFU SS1696)分别对BALB/c小鼠进行两轮免疫,采集血清检测特异性抗体水平,分别用3种菌株致死剂量攻毒后观察小鼠免疫保护率,同时用亚致死剂量攻毒三价苗免疫组,测定小鼠血、脑、肺、脾的组织载菌量和细胞因子IL-6、IL-12水平,并观察脑、肺、脾、肾中的组织病理变化。结果显示:3株疫苗候选菌株的毒力基因鉴定分别为SS1803:gapdh^(+)/sly^(+)/fbps^(+)/orf2^(+)/mrp^(-)/89K^(-)/gdh^(+)/epf^(+),SS1803024:gapdh^(+)/sly^(+)/fbps^(+)/orf2^(+)/mrp^(-)/89K^(-)/gdh^(+)/epf^(-),SS1696:gapdh^(+)/sly-/fbps^(+)/orf2^(+)/mrp^(-)/89K^(-)/gdh^(+)/epf^(-)。单价和三价疫苗免疫组均能产生对应免疫血清型的IgG抗体,以产生IgG1型抗体为主。三价疫苗免疫组能对2、3、9型3个菌株攻毒分别提供83.3%、66.7%和66.7%的保护率,能显著降低感染后小鼠组织中的载菌量,降低血清炎性因子水平和组织病变程度。本研究筛选临床流行率高的2、3、9型强毒株,联合制备三价灭活疫苗,能够对小鼠提供良好的免疫保护力,为猪链球菌多价疫苗的研发提供新的材料。