Impact of maternal and pre-existing antibodies on immunogenicity of inactivated rotavirus vaccines

Rotavirus (RV) is a major pathogen causing severe diarrhea in infants and children aged less than 5 years. Vaccination is an economically feasible and effective strategy to prevent rotavirus infections. However, immune efficacy of live vaccines could be interfered by maternal antibodies and pre-existing antibodies of children. To develop an inactivated rotavirus vaccine (IRV), we had previously isolated a wild-type human rotavirus strain ZTR-68-A (G1P[8]) from the fecal samples of infants having severe diarrhea in a region endemic for the presence of this pathogen. In our present study, we assessed whether the presence of maternal and pre-existing antibodies in newborn BALB/c mice affected the immunogenicity of IRV administered to these animals. Our results indicate that maternal antibodies, generated from either vaccine immunization or rotavirus infection, showed partial influence with the immune responses generated by two doses of IRV vaccination. Increasing the number of immunizations can significantly improve the titer of serum neutralizing antibody and a seroconversion rate of up to 100%. In newborn mice, single-virus infection did not elicit detectable levels of serum neutralizing antibodies. After an IRV vaccination, the immune responses of these mice remained unaffected, with no significant differences in titers compared with those of control-group mice. In summary, choosing a suitable immunization dose and dosing frequency is essential for the immune effectiveness of IRV. The results of this study will provide animal experimental support for the IRV clinical research in future.     

Single-cell transcriptome atlas reveals protective characteristics of COVID-19 mRNA vaccine

Messenger RNA (mRNA) vaccines are promising alternatives to conventional vaccines in many aspects. We previously developed a lipopolyplex (LPP)-based mRNA vaccine (SW0123) that demonstrated robust immunogenicity and strong protective capacity against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in mice and rhesus macaques. However, the immune profiles and mechanisms of pulmonary protection induced by SW0123 remain unclear. Through high-resolution single-cell analysis, we found that SW0123 vaccination effectively suppressed SARS-CoV-2-induced inflammatory responses by inhibiting the recruitment of proinflammatory macrophages and increasing the frequency of polymorphonuclear myeloid-derived suppressor cells. In addition, the apoptotic process in both lung epithelial and endothelial cells was significantly inhibited, which was proposed to be one major mechanism contributing to vaccine-induced lung protection. Cell−cell interaction in the lung compartment was also altered by vaccination. These data collectively unravel the mechanisms by which the SW0123 protects against lung damage caused by SARS-CoV-2 infection.     

人埃可病毒20型KM/EV20/2010分离株的全基因组序列分析

目的 对人埃可病毒20型(ECHO20)KM/EV20/2010分离株全基因组进行序列测定, 并分析其分子变异和进化特点。方法 设计针对KM/EV20/2010引物, 提取病毒RNA, RT-PCR扩增和序列测定获得全基因序列。利用Mega 4.1、RDP3和SimPlot 3.5.1软件分析全基因序列。结果 KM/EV20/2010病毒株基因组全长7 395 bp个核苷酸(nt), 5''端和3''端分别为744 nt和96 nt的非编码区, 5''和3''非编码区间为一个6 549 nt长的开放阅读框, 编码一个含2 183个氨基酸的多聚蛋白, 编码区内未见核苷酸的插入或缺失。与GenBank中现有唯一1株ECHO20 JV-1原型株全基因组序列相比对, 核苷酸同源性为80.1%, 氨基酸同源性为96.7%;构建基于全长VP1基因序列的进化树图并进行基因分型分析, ECHO20可分为6个基因型, 中国分离株分属Ⅲ和Ⅳ基因型, 其中KM/EV20/2010属于基因型Ⅳ, 且6个基因型之间核苷酸的差异为9.4%～21.7%。基于全基因组序列的种系进化分析提示KM/EV20/2010分离株与ECHO20原型株JV-1遗传距离很远, 未与原型株JV-1聚簇分布, 而与ECHO30病毒株遗传距离较近。分析发现KM/EV20/2010序列在非结构区可能存在重组。结论 中国ECHO20可分为6个基因型, KM/EV20/2010分离株属于Ⅳ基因型。     

野生树鼩肠道蠕虫感染调查及分析

目的调查野生树鼩(Tupaia belangeri Chinensis)感染肠道蠕虫的主要种类并进行鉴定,为今后树鼩寄生虫检测提供形态学参考,为实验树鼩寄生虫控制提供依据。方法采集203只野外来源的树鼩新鲜粪便,虫卵采用常规粪便直接涂片以及孵化后显微镜观察;绦虫采用压片、固定染色,以及线虫经透明后体视镜观察,虫卵与成虫相对应鉴定。结果野生树鼩肠道蠕虫的总感染率为75.86%,主要感染种类有3种,经鉴定为长膜壳绦虫、奇口线虫和粪类圆线虫,感染率分别为27.67%,30.06%和51.52%。三种蠕虫的混合感染率为4.55%。两种线虫虫卵在树鼩粪便中多为含胚胎形态。结论野生树鼩肠道蠕虫的感染率较高。对野外引入的新种源必须隔离检疫,进行针对性的药物治疗,才能有效地控制肠道寄生虫病的传播。     

Distribution of KIR genes in Han population in Yunnan Province: comparison with other Han populations in China

Killer cell immunoglobulin‐like receptors (KIRs) show extensive variation among different populations. In this study, 404 unrelated individuals in Han population in Yunnan Province, China, were genotyped for the presence or the absence of 16 KIR genes using the multiplex PCR‐SSP method. Our data showed that the inhibitory gene frequency of genes KIR2DL1, KIR2DL3, KIR3DL1, KIR2DL5 and KIR2DL2 was 0.930, 0.889, 0.789, 0.206 and 0.095, respectively, and the activating gene frequency of KIR2DS4, KIR3DS1, KIR2DS1, KIR2DS5, KIR2DS2 and KIR2DS3 was 0.795, 0.218, 0.196, 0.165, 0.095 and 0.087, respectively. In all, 44 distinct KIR genotypes were identified; genotype 1 was predominant with a frequency of 0.478, followed by genotypes 2 and 8 with a frequency of 0.121 and 0.077, respectively. Haplotype A outnumbered haplotype B by 2.39:1. In addition, phylogenetic tree and multidimensional scaling analysis (MDS) based on KIR genes in populations including Asian, African and Caucasians have been performed. Neighbour‐joining tree analysis and the MDS plot showed that Han populations were clustered together with Asian and were separate from other populations. The Han populations in China were separated into northern and southern groups; the Yunnan Han population investigated in this study was clustered in the southern group. These results implied that the difference between northern and southern Han populations might reflect responses to a variety of locally acting epidemiological challenges.     

哺乳动物中天然抗病毒RNAi的研究现状及其应用前景

RNA干扰（RNA interference,RNAi）能够特异性沉默与小干扰RNA（small interfering RNA,siRNA）互补的靶mRNA,在果蝇、线虫、植物和哺乳动物中发挥重要的抗病毒免疫功能.此文概述了抗病毒RNAi途径的发现、抗病毒RNAi的免疫机制、病毒编码的RNAi抑制子、天然抗病毒免疫RNAi在哺乳动物中的研究现状以及抗病毒RNAi的应用前景.     

SIGIRR modulates the inflammatory response in the brain

One of the more recently described members of the interleukin-1 (IL-1) receptor family, single-Ig-interleukin-1 related receptor (SIGIRR), has been identified as a negative regulator of inflammation in several tissues. It modulates the responses triggered by stimulation of Toll-like receptor (TLR) 4 and IL-1 in several peripheral cell types, possibly in an NFκB-dependent manner. Consistently, responses to lipopolysaccharide (LPS) are exaggerated in SIGIRR-deficient mice and the symptoms of experimental inflammatory conditions are more profound in these animals. Here, we set out to establish whether the absence of SIGIRR was associated with inflammatory changes in the brain and report that, LPS-induced a greater effect on CD40 and ICAM mRNA in mixed glia prepared from SIGIRR^?/?, compared with wildtype mice. This was associated with parallel changes in TNFα and IL-6 at mRNA and protein levels, an effect which was observed in purified microglia but not astrocytes. Similarly, LPS exerted a more profound effect on microglial activation and cytokine production in hippocampal tissue prepared from SIGIRR^?/?, compared with wildtype mice. The effect of LPS on exploratory behaviour was also accentuated in SIGIRR^?/? mice. The evidence suggests that these changes are a likely consequence of increased hippocampal expression of CD14 and TLR4, and NFκB activation in SIGIRR^?/? mice.     

从临床肺炎死亡树鼩中分离到致病性大肠埃希菌

目的对6例1月内因肺炎死亡的树鼩采样进行病原菌分离培养鉴定分析。方法解剖死亡树鼩,利用无菌刀片切开肺组织,用无菌接种环插入肺内采样接种于营养琼脂培养基,另取两份样品进行细菌涂片革兰氏染色和抗酸染色。培养出来的细菌进行进一步分离和菌落生长情况的观察,并经革兰氏染色、抗酸染色、氧化酶试验、生化编码鉴定和9种药敏试验,初步确定树鼩肺部感染的致病菌及其药敏情况。结果样本革兰氏染色见到大量阴性杆菌,抗酸染色结果显示为非结核分枝杆菌,大小约为0.2μm×2～6μm。营养琼脂培养6例样品中均仅见1株旺盛生长的细菌,进一步分离培养经革兰氏染色为阴性杆菌,抗酸染色为非结核分枝杆菌,大小和染色结果与样本涂片相同,经鉴定为致病性大肠埃希菌。药敏试验表明该菌对头孢哌酮,呋喃妥因,氨苄西林,阿米卡星,氧氟沙星,诺氟沙星,磺胺甲噁唑/甲氧苄定高度敏感;对庆大霉素和青霉素G为低度敏感。结论 6例树鼩死亡原因均为细菌性肺炎,病原菌初步鉴定为致病性大肠埃希菌。药敏实验筛选出的药物可为临床治疗树鼩该类病例用药提供指导。     

Assessment of HCV genotypes in Yunnan Province of Southwest China

Recently, we reported that the frequency of hepatitis C virus (HCV) genotypes and subtypes has rapidly changed among intravenous drug users (IDUs) in Yunnan Province over the last 5 years; this is especially true for subtype 6a which has increased in frequency from 5 to 15%. Here, we assessed 120 HCV-positive plasma samples from the general population (GP). HCV NS5B fragments were amplified and sequenced by PCR. We identified four HCV genotypes (1, 2, 3 and 6) and seven HCV subtypes (1b, 2a, 3a, 3b, 6a, 6n, and 6k) in this population. Genotype 3 was predominant, with a distribution frequency of 0.484, followed by genotype 1 (0.283), genotype 6 (0.133) and genotype 2 (0.100). HCV subtypes 3b (frequency 0.292) and 1b (frequency 0.283) were the most common subtypes. A comparison of the current data with previous results reported for IDUs showed that the distribution frequencies of genotypes 1, 2 and 6 were significantly different between patients in the GP and IDUs (P < 0.05). Among the HCV subtypes, the distribution frequencies of 1b, 2a, 6a, and 6n were significantly different between patients in the GP and IDU groups (P < 0.05). Moreover, Phylogenetic analyses showed that HCV subtype 6a strains isolated from IDUs and the GP were intermixed and not separately clustered. HCV subtype 6a was predominant not only among IDUs but also among those in the GP in the Guangdong Province and Vietnam. However, HCV subtype 6a was predominant only among IDUs and not among those in the GP in the Yunnan and Guangxi Provinces. Our results indicate that the HCV subtype 6a could rapidly spread across China.