疫苗接种效应影响下的SVEIR模型的动力学分析

[目的]由于流行病会随着时间的变化而发生变化,因此,结合现实情况,研究一种受接种疫苗比率和免疫率影响的带时变性质的SVEIR疾病传播模型的平衡点的动力学性质.[方法]首先,通过构建动力学模型研究平衡点的存在性;其次,利用下一代矩阵法得出模型的基本再生数R0和有效再生数Re;最后,通过Lyapunov定理和Routh-Hurwitz判别方法对病毒的基本再生数和有效再生数进行稳定性分析.[结果]通过python数值仿真实验,得出当R0<1时,疾病会消失;当R0>1时,流行病会转化为地方流行病;当R0=1时,系统会出现临界分岔现象.[结论]接种疫苗是疾病防控的关键措施之一.R0的取值决定流行病的演化结果.

流行性腮腺炎减毒活疫苗接种的现状及其免疫效应

流行性腮腺炎是一种常见的病毒感染性传染病，其危害越来越被人们所重视。1967年研制成功减毒活疫苗并开始广泛使用后流行性腮腺炎发病率明显下降，但在没有应用疫苗的国家中仍保持高发病率。我国缺少流行性腮腺炎疫情的完整资料，疫苗接种率不高，又缺乏系统免疫规划和高效疫苗，目前流腮在我国远未被控制。全世界有109个国家将流行性腮腺炎疫苗纳入国家免疫规划，常用的疫苗株至少有10种以上，近期应用最为广泛的疫苗毒株有Jeryl-Lynn、RIT4385、L-3、L-Zagrab、S79等，均有良好的免疫效应。但儿童（二剂次）接种率〈80％，不但不能阻止暴发和流行，还会导致流行年龄高峰向后推移。免疫效应最突出的毒株是L3系列、Urabe株等低度减毒株免疫原性较好但往往与接种疫苗后的脑膜炎有关；高度减毒株较安全，但免疫原性可能较差。几株系列有免疫效应好且安全的特长国产疫苗效应较几、L3系列疫苗差。

具有接种效应带时变时滞的SVEIR模型的稳定性分析

考虑了一类受接种疫苗影响的带时变时滞的SVEIR疾病传播模型,针对不同取值下的病毒基本再生数R0,分别采取Liapunov函数法和Routh-Hurwitz判别法对模型平衡点的存在性、稳定性、分岔性进行研究。最后对不同的R0进行数值模拟,验证理论分析结果的正确性。

草鱼赤皮病的免疫效应研究

采用0．5％福尔马林灭活草鱼赤皮病病原菌分别制成浸泡疫苗、注射疫苗和VI服微囊疫苗，然后以相应的疫苗分别浸泡（含菌数为1．5×107cfu／ml的菌苗溶液）3～5cm当年夏花草鱼、0．2ml／尾注射（含菌数为1．5×108cfu／ml的菌苗）10g左右的草鱼、16g／组·次微囊疫苗混合饲料（含2％微囊疫苗）投喂10g左右的草鱼。接种免疫后，分别于第21d、35d、49d、63d及77d，通过检测实验对象的血清和采用活菌攻毒的方法，探讨了灭活菌苗对预防草鱼赤皮病的效果。结果显示，所制疫苗3种免疫途径都有免疫效果。全菌灭活疫苗浸泡免疫、注射免疫和微囊化疫苗口服免疫的抗体滴度（凝集抗体效价）平均分别为1：19、1：190、1：62；用荧光假单胞菌活菌进行浸泡和注射攻毒，结果显示，3种免疫途径均产生良好的保护效应。浸泡和注射攻毒后其免疫保护率分别为41．6％和40．0％、83．4％和80％、58．4％和53．3％。

Establishment and Preliminary Application of a Rapid Fluorescent Focus Inhibition Test (RFFIT) for Rabies Virus

The World Health Organization (WHO) standard assay for determining levels of the rabies virus neutralization antibody (RVNA) is the rapid fluorescent focus inhibition test (RFFIT), which is used to evaluate the immunity effect after vaccination against rabies. For RFFIT, CVS-11 was used as the challenge virus, BSR cells as the adapted cells, and WHO rabies immunoglobulin (WHO STD) as the reference serum in this study. With reference to WHO and Pasteur RFFIT procedures, a micro-RFFIT procedure adapted to our laboratory was produced, and its specificity and reproducibility were tested. We tested levels of RVNA in human serum samples after immunization with different human rabies vaccines (domestic purified Vero cell rabies vaccine (PVRV) and imported purified chick embryo cell vaccine (PCECV)) using different regimens (Zagreb regimen and Essen regimen). We analyzed the levels of RVNA, and compared the immune efficacy of domestic PVRV and imported PCECV using different immunization regimens. The results showed that the immune efficacy of domestic PVRV using the Zagreb regimen was as good as that of the imported PCECV, but virus antibodies were generated more rapidly with the Zagreb regimen than with the Essen regimen. The RFFIT procedure established in our laboratory will enhance the comprehensive detection ability of institutions involved in rabies surveillance in China.

Evaluation of Efficacy of Stabilizers on the Thermostability of Live Attenuated Thermo-adapted Peste des petits ruminants Vaccines

In this study, thermo-adapted （Ta） PPR vaccines were assessed for their stability at 25, 37, 40, 42 and 45℃ in lyophilized form using two extrinsic stabilizers {lactalbumin hydrolysate-sucrose （LS） and stabilizer E} and in reconstituted form with the diluents （1 mol/L MgSO4 or 0.85% NaC1）. The lyophilized vaccines showed an expiry period of 24-26 days at 25℃, 7-8 days at 37℃ and 3-4 days at 40℃. LS stabilizer was superior at 42℃ with a shelf-life of 44 h, whereas in stabilizer E, a 40 h shelf-life with a comparable half-life was observed. At 45 ℃, the half-life in stabilizer E was better than LS and lasted for 1 day. Furthermore, the reconstituted vaccine maintained the titre for 48 h both at 4℃ and 25℃ and for 24-30 h at 37℃. As both the stabilizers performed equally well with regard to shelf-life and half-life, the present study suggests LS as stabilizer as a choice for lyophilization with 0.85% NaCldiluent, because it has better performance at higher temperature. These Ta vaccines can be used as alternatives to existing vaccines for the control of the disease in tropical countries as they are effective in avoiding vaccination failure due to the breakdown in cold-chain maintenance, as this vaccine is considerably more stable at ambient temperatures.

Evaluation of the Pathogenicity and Immune Response of Nervous Necrosis Virus Isolated in Vietnam

Eight strains of nervous necrosis virus （NNV） isolated in Vietnam were used to detect the pathogenicity and immune response in sea bass （SB）. All strains induced cytopathic effect in SB cell line, complete destruction of monolayer of cells appeared after seven days post infection （dpi）. Virus titer was different for each strain, TCIDso ranged from 102.7 to 1069, and LDs0 from 1015 to 1075. Five NNV strains named QN 02, QN 05, QN 07, ND 11 and KH 05 had higher virulence than the other three, the first causing 100% mortality in experimental fish 3-5 dpi. NNV KH 05 had the highest antigenic similarity, and it was inactivated completely by 0.2% formalin, 0.002 mol/L binary ethylenimine （BEI） and 0.1% beta-propiolactone. The neutralization antibody titer obtained in fish of groups immunized by BEI 0.002 M and beta-propiolactone 0.1% inactivated virus was four to eight times higher than that of the group treated with the formalin inactivated virus. The antibody titer in fish immunized with beta-propiolactone inactivated virus was more persistent. The efficacy of vaccines developed from beta-propiolactone inactivated virus and aluminium hydroxide （AH） or aluminum phosphate （AP） was observed by intramuscularly immunizing Epinephelusfuscoguttatus size 1.5 cm. Neutralizing antibodies appeared in vaccinated fish on 10th day post-immunization （dpi） at a dilution of 1：16; 1：32 and highest levels were reached on 30-45 dpi, at dilutions of 1：256 and 1：512, after treatment with AH and AP vaccine, respectively. The relative percent of survival （RPS） of vaccine at 30 dpi was highest with challenge doses 0.2-1 × 10^6.8 TCIDs0, the RPS varied from 80%-83.3% in both groups of AH and AP immunization. This result provides the basis for developing a vaccine against NNA disease.

重大疾病疫苗研究的关键科学问题——第224期双清论坛学术综述

预防性疫苗的接种是针对传染病最经济和最有效的防治措施,被评为二十世纪最伟大的公共卫生成就。疫苗也被认为可能是肿瘤、代谢性疾病、退行性疾病等慢病最具潜力的防治手段。疫苗涉及国家安全,是国家战略医药产业之一,因此提升疫苗研发能力必须作为国家战略进行布局。2019年国家自然科学基金委员会医学科学部、生命科学部、信息科学部、化学科学部与政策局联合主办了“重大疾病疫苗研究的关键科学问题”双清论坛,专家围绕疫苗免疫原、佐剂、递送系统、疫苗效应的免疫保护性与免疫记忆机制、疫苗研制的新策略与新系统与技术进展、疫苗流行病学、疫苗评价技术体系建立等主题研讨,分析了疫苗研究面临的挑战,提出了我国重大疾病疫苗研究的战略方向。本文为这次双清论坛的学术综述。

细菌鞭毛蛋白在Treg表位肽自身免疫性风湿病治疗中的应用前景

用调节性T细胞(Treg)表位肽进行免疫、激发和诱导表位肽特异的Treg细胞,抑制过强的自身免疫应答,从而建立起新的免疫稳态,是一个很有前景的自身免疫性风湿病的治疗方案,然而小分子的表位肽通常很难在体内有效激发出表位肽特异的免疫应答。细菌鞭毛蛋白是固有免疫系统的一种激动剂,在作为偶联载体时对偶联的抗原有极强的佐剂作用,在特定情况下能够激发和诱导Treg细胞。因此,如果将Treg细胞表位肽与细菌鞭毛蛋白共价偶联,偶联体应可通过鞭毛蛋白本身的作用,以及鞭毛蛋白对Treg细胞表位肽的佐剂作用,有效增强基于Treg细胞的免疫应答,从而增强对自身免疫性风湿病的免疫治疗效果。