DC-SIGN在树突状细胞传播HIV-1中作用的实验研究

目的探讨DC—SIGN在树突状细胞（DC）传播HIV-1中的作用。方法用M嗜性或T嗜性HIV-1原代分离株分别刺激未成熟DC（immature DC，iDC））和成熟DC（mature DC，mDC），数量与DC相同的CD4^T细胞作为对照组，与活化的CD4^＋T细胞共培养，用ELISA方法定量检测第4、7、10、14天共培养上清中p24抗原，观察Dc在传播HIV-1的作用。预先加入抗DC—SIGNMcAb和，或抗ICAM-3McAb，观察抗DC-SIGNMcAb和抗ICAM-3McAb对DC传播HIV-1作用的影响。结果用M嗜性HIV-1刺激的iDC以及用M和T嗜性HIV-1刺激的mDC的共培养上清中p24含量均随培养时间延长逐渐增加，显著高于对照组（P=0．001）。加入抗DC．SIGNMcAb后，共培养上清p24抗原明显降低；加入抗ICAM-3McAb后上清中p24抗原并不减少。用T嗜性HIV-1刺激的iDC共培养上清中p24含量不随培养时间延长逐渐增加，与对照组相比差异无统计学意义。结论iDC具有传播M嗜性HIV-1的作用，但不具有传播T嗜性HIV-1的作用；mDC既能将M嗜性也能将T嗜性HIV-1传播给CD4^T细胞。抗DC-SIGN McAb能够抑制DC传播HIV-1的作用，提示DC-SIGN在DC向T细胞播散HIV-1过程中可能发挥重要作用。     

A novel combined vaccine based on monochimeric VLP co-displaying multiple conserved epitopes against enterovirus 71 and varicella-zoster virus

Chicken pox and hand, foot and mouth disease (HFMD) are two major infectious diseases that mainly affect infants and children, causing significant morbidity annually. Varicella-zoster virus (VZV) and enterovirus 71 (EV71), respectively, are the principal epidemic pathogens causing these two diseases. To investigate the possibility of developing a novel combined vaccine to prevent chicken pox and HFMD, we constructed three chimeric virus-like particles (VLPs) (termed HBc-V/1/2, HBc-2/V/1 and HBc-1/2/V) based on the hepatitis B core antigen (HBc) carrier that display epitopes derived from VZV-gE, EV71-VP1, and EV71-VP2 in a varied tandem manner. The chimeric HBc can self-assemble into VLPs with these three epitopes displayed on the surface of particles. Epitope-specific antibody characterization suggested that HBc-V/1/2 elicits a balanced antibody response toward these three epitopes, and no immune interference was observed between the three epitopes. Importantly, the anti-HBc-V/1/2 sera could simultaneously neutralize VZV and EV71 and cross-neutralize coxsackievirus A16 (CVA16), another major pathogen causing HFMD. Moreover, the anti-HBc-V/1/2 sera protected neonatal mice from lethal challenge of EV71 and CVA16. Collectively, our study not only demonstrated that HBc-V/1/2 is a promising candidate combined vaccine for HFMD and Chicken pox but also provides a novel strategy for the design of combined vaccines.     

Recombinant Lactobacillus casei expressing Clostridium perfringens toxoids α, β2, ε and β1 gives protection against Clostridium perfringens in rabbits

The present study used Lactobacillus casei ATCC 393 as antigen delivery system to express C. perfringens toxoids α-β2-ε-β1 to construct the recombination Lactobacillus casei pPG-2-α-β2-ε-β1/L. casei 393. After being induced by 1% xylose, the specificity and integrity of recombinant strain were determined by Western-blotting. Rabbits as native animal model were immunized orally with pPG-2-α-β2-ε-β1/L. casei 393 and the titers of specific IgG and sIgA were determined by ELISA. The result showed that oral administration with the recombinants could elicit both local mucosal and systemic immune responses. The proliferation of spleen lymphocytes in rabbits immunized with pPG-2-α-β2-ε-β1/L. casei 393 was observed. Levels of IL-4 and IFN-γ produced were significantly higher in lymphocytes isolated from the vaccine group than those from the control groups. Flow cytometry assay showed that both the percentages of CD4 + T cells and CD8 + T cells from the vaccine group were significantly increased than the control groups. All these results showed that immunizing with recombinants can elicit both humoral immunity and cellular immunity. Besides, in order to determine the effectiveness of oral immunization with pPG-2-α-β2-ε-β1/L. casei 393, rabbits of vaccine group and control groups were challenged with 1 × LD₁₀₀ unit of culture filtrate of C. perfringens type C and type D toxins respectively. After challenge, 100% of the immunized rabbits survived, while the rabbits of the control group were killed within 48 h. Observation on histopathology showed that histopathological changes were obviously found in heart, liver, spleen, lung, kidney, intestine and brain of rabbits from the control groups, while no apparent histopathological change was observed in the vaccine group. All the results show that pPG-2-α-β2-ε-β1/L. casei 393 can elicit effective immunoprotection against C. perfringens. All of these suggest that the use of pPG-2-α-β2-ε-β1/L. casei 393 can be regarded as candidate for the development of a vaccine against C. perfringens.     

Could HLA-DRB1 be the protective locus in rheumatoid arthritis?

Extensive studies in different ethnic groups have associated the susceptibility to development of rheumatoid arthritis (RA) with the third hypervariable region of the major histocompatibility complex (MHC) HLA-DRβl molecule. On the basis of recent findings in the experimental mouse model of collagen-induced arthritis. Eric Zanelli, Miguel Gonzalez-Gay and Chella David propose that the HLA-DRB1 locus is associated with protection to RA and that the actual arthritogenic peptide-presenting molecule is HLA-DQ. Thus, the development of RA would depend upon the expression of the susceptible DQ allele and the nonprotective DRB1 alleles, along with environmental factors that trigger the autoimmune process.     

Interest in Long-Acting Injectable PrEP in a Cohort of Men Who have Sex with Men in China

Long-acting injectable (LAI) formulations of antiretrovirals (ARVs) as pre-exposure prophylaxis (PrEP) could be an attractive alternative for men who have sex with men (MSM) who are interested in ARV-based biomedical prevention but will not use a daily pill. This study investigated interest in LAI-PrEP in a cohort of MSM in China and characterized how MSM willing to use only injectable PrEP differed from MSM who would use PrEP regardless of modality or not at all. Demographic, behavioral, and risk perception measures were collected and associations investigated. A licensed LAI-PrEP agent would increase the proportion interested in PrEP by 24.5% over oral PrEP alone. Combining interest in oral and injectable PrEP, 78.5% of the sample could be covered if reported interest in PrEP translated into actual uptake. Partnership factors differentiated those who would be willing to use only LAI-PrEP versus any PrEP modality, while higher self-perception of risk was associated with interest in LAI-PrEP versus no PrEP. The addition of a second PrEP modality could yield increased population coverage of PrEP. Social and behavioral research should be undertaken in parallel with clinical development of injectable PrEP agents to identify characteristics of those who are not interested in oral PrEP but would take advantage of ARV-based prevention with the introduction of an injectable product.     

HIV感染后CD8~+T细胞表面NK相关受体表达的变化

目的深入了解人类免疫缺陷病毒(human immunodeficiency virus,HIV)感染后CD8+T细胞表面NK相关受体表达的变化。方法选取25例未经高效抗逆转录病毒治疗的HIV感染者、11例AIDS患者、15例进行高效抗逆转录病毒治疗(highly active antiretroviral therapy,HAART)者和13例HIV抗体阴性健康对照,用流式细胞仪检测研究对象外周血CD8+T细胞表面NKG2D、NKG2A和KIR3DL1的表达。结果 HIV感染后CD8+T细胞表面NKG2D表达的百分比显著低于健康对照,NKG2D+NKG2A-表达的百分比随疾病进展逐渐下降,且NKG2D+NKG2A-表达的百分比与CD4+T细胞的绝对数量呈正相关。AIDS患者CD8+T细胞表达NKG2A显著高于其它各组,随着疾病的进展CD8+T细胞表达NKG2A+NKG2D-百分比逐渐上升,AIDS患者显著高于其它各组,经抗逆转录病毒治疗后下降至健康对照的水平,且NKG2A+NKG2D-表达的百分比与CD4+T细胞的绝对数量呈负相关。HIV感染后CD8+T细胞KIR3DL1+表达的百分比较健康对照并无显著差异。结论 HIV感染机体后,CD8+T细胞NK相关受体表达变化与疾病进展相关,抗病毒治疗后可恢复其变化。     

视网膜光凝术联合中药治疗糖尿病性视网膜病变

目的:探讨口服滋阴凉血散瘀汤联合激光治疗糖尿病性视网膜病变的临床疗效。方法:采用口服滋阴凉血散瘀汤联合视网膜光凝治疗糖尿病性视网膜病变患者,以单纯视网膜光凝为对照组,对比两组患者在治疗后1,6,12mo的视力、视野及新生血管的变化情况。结果:口服滋阴凉血散瘀汤联合光凝治疗组患者12mo时视力提高(62.3%vs43.1%,P=0.037),视野改变(17.0±3.7vs14.9±3.7,P=0.002)及新生血管退缩情况(67.2%vs48.3%,P=0.036)均优于对照组患者。结论:滋阴凉血散瘀汤联合激光治疗糖尿病性视网膜病变较单纯激光治疗更有效。