Methodological advances in the design of peptide-based vaccines

The tremendous advances in genomics, recombinant DNA technology, bioengineering and nanotechnology, in conjunction with the development of high-end computations, have been instrumental in the process of rational design of peptide-based vaccines. The use of peptide vaccines was limited owing to their inherent instability when systemically administered; however, advanced formulation techniques have been developed for their systemic delivery, thereby overcoming their degradation, clearance, cellular uptake and off-target effects. With the rise of sophisticated immunological predictors and experimental techniques, several methodological advances have occurred in this field. This review examines contemporary methods to identify and optimize epitopes, engineer their immunogenic properties and develop their safe and efficient delivery into the host.     

The co-expression characteristics of LAG3 and PD-1 on the T cells of patients with breast cancer reveal a new therapeutic strategy

Many studies have shown a special interaction between LAG3 and PD-1 in T cell inhibition, while the co-expression and effect of LAG3 and PD-1 on T cells in breast cancer patients are still not very clear. Here, with strict exclusion criteria, 88 patients with breast cancer and 18 healthy controls were enrolled. The percentages of LAG3⁺PD-1⁺ T cells in their peripheral blood (PBL) and tumor infiltrating T cells (TIL) were analyzed by flow cytometry, which showed an increase in TILs but no difference in PBLs and presented differences in TILs in different molecular subtypes (P < 0.05). In triple-negative breast cancer (TNBC), the highest percentages were observed, while in ER+/PR+ breast cancer, the lowest percentages were observed; however, these percentages were not different in different clinical stages (P > 0.05). Immunohistochemical staining showed that the expression of their ligands, PD-L1, MHC class II molecular and FGL1, was inconsistent in different molecular subtypes and clinical stages. Analysis of the functions of T cells with different phenotypes showed that the proliferation and secretion capacity of LAG3⁺PD-1⁺ T cells was obviously exhausted, with more than a two-fold of decrease compared with the groups of single positive LAG3 or PD-1 (P < 0.05). Finally, in a mouse model of TNBC, the dual blockade of LAG3 and PD-1 was indicated to achieve a better anti-tumour effect than either one alone (P < 0.05), which may provide a new strategy for the immunoregulatory treatment of patients with TNBC in the future.     

Analysis of Single Nucleotide Polymorphisms in the Gamma Block of the Major Histocompatibility Complex in Association with Clinical Outcomes of Hematopoietic Cell Transplantation: A Center for International Blood and Marrow Transplant Research Study

HLA haplotype mismatches have been associated with an elevated risk of acute graft-versus-host disease (aGVHD) in patients undergoing HLA-matched unrelated donor (URD) hematopoietic cell transplantation (HCT). The gamma block (GB) is located in the central MHC region between beta and delta blocks (encoding HLA-B and -C and HLA-DQ and -DR antigens, respectively) and contains numerous inflammatory and immune regulatory genes, including Bf, C2, and C4 genes. A single-center study showed that mismatches in SNPs c.2918+98G, c.3316C, and c.4385C in the GB block (C4 SNPs) were associated with higher risk of grade III-IV aGVHD. We investigated the association of GB SNP (GBS) mismatches with outcomes after 10/10 and 9/10 URD HCT (n?=?714). The primary outcome was acute GVHD. Overall survival, disease-free survival, transplantation-related mortality, relapse, chronic GVHD, and engraftment were also analyzed. DNA samples were GBS genotyped by identifying 338 SNPs across 20 kb using the Illumina NGS platform. The overall 100-day incidence of aGVHD grade II-IV and II-IV were 41% and 17%, respectively. The overall incidence of matching at all GBSs tested and at the C4 SNPs were 23% and 81%, respectively. Neither being matched across all GB SNPs tested (versus mismatched) nor having a higher number of GBS mismatches was associated with transplantation outcomes. There was no association between C4 SNP mismatches and outcomes except for an unexpected significant association between having 2 C4 SNP mismatches and a higher hazard ratio (HR) for relapse (association seen in 15 patients only; HR, 3.38, 95% confidence interval, 1.75 to 6.53; P?=?.0003). These data do not support the hypothesis that mismatching at GB is associated with outcomes after HCT.     

Are rats more human than mice?

In contrast to rats, mouse models are nowadays generally used for the investigation of immune responses and immune-mediated diseases, there are many different strains and mouse-specific tools available, and it is easy to generate transgenic and constitutive or inducible knockout mice for any gene. Many immune markers and mechanisms have been detected in mice and have been introduced as gold standard in immunology, however, some turned out to be not unconditionally transferable to the human immune system.Rats have been used more frequently in former days but are mostly outstripped by mice due to the fact that fewer strains are available, they need more space than mice, are more expensive to maintain and breed, and it is extremely difficult to generate transgenic or ko-rats. Consequently, the choice of rat-specific diagnostic tools like antibodies is quite poor and most researchers have switched to mouse models for the investigation of immune mechanisms, while rats are still widely used for toxicology by the pharmaceutical industry. However, it should be taken into consideration that there are some immunological similarities between rats and humans that are not presented in mice. Some of them like MHC class II and Foxp3 expression by activated effector T cells we have detected during our research on the immune response of rat models of experimental autoimmune uveitis.     

中药五倍子根管糊剂的组织相容性实验研究

目的：对中药五倍子根管糊剂进行动物皮下埋植实验,评价其组织相容性。方法：在无菌手术条件下将实验材料植入家兔背部皮下,以临床常用根管糊剂（含甲醛根管糊剂、AHPlus糊剂）做对照,埋植后的第1、4和12周分期处死动物,观察埋植体周围组织的炎细胞浸润数和纤维包膜厚度。结果：各实验组埋植体周围组织炎症反应程度随时间递增而降低。其中,五倍子根管糊剂降低速率最高,4周时炎症反应明显低于含甲醛糊剂组和AHPlus组（P〈0.05）;12周时与空白对照组无显著性差异（P〉0.05）。其次为AHPlus组,但到12周时仍有一定的炎症反应,与空白对照组相比有显著性差异（P〈0.05）。含甲醛根管糊剂组降低最慢且在12周时仍有较重的炎症反应。结论：五倍子根管糊剂具有良好的组织相容性。     

液氮冷冻对成骨细胞免疫原性影响的实验研究

目的 :探讨液氮冷冻对成骨细胞免疫原性的影响。方法 :体外培养成骨细胞 ,传代鉴定后液氮冻存 3个月 ,复苏。利用流式细胞仪 (FCM ) ,通过间接免疫荧光技术测定冻存前后成骨细胞的免疫原性。结果 :体外培养细胞经鉴定为成骨细胞 ,液氮冻存 3个月后存活率 >90 %。FCM测定结果表明冻存后成骨细胞的免疫原性显著降低 (P <0 .0 1)。结论 :液氮冷冻是一种理想的降低成骨细胞免疫原性的方法     

Distribution of interleukin-2 receptor α-chain and cells expressing major histocompatibility complex class II antigen in chronic human periapical lesions

In situ distribution of CD2⁺ T-lymphocytes, CD4⁺ and CD8⁺ T-cell subsets, CD14⁺ macrophages, interleukin-2 receptor α-chain (IL-2Rα) and class II major histocompatibility complex antigen (major histocompatibility complex class II, HLA-DR) expressing cells were determined in 14 chronic human periapical granulomas by imrnunohistochemical method using monoclonal antibodies. CD2⁺ lymphocytes were rather evenly distributed within the classical granulation tissue and comprised 55% of the mononuclear cells. Macrophages were distributed all over the periapical area, but their proportion was much less than that of T lymphocytes. Both small, lymphocyte-like mononuclear cells and larger mononuclear cells resembling macrophages displayed mild to strong circumferential staining with the anti-HLA-DR antibody. The majority of lymphocytes expressed IL-2Rα indicating the activated state of T cells within the lesion.