Immunogenicity Research Articles

Comparison of a second TNFi vs other biologic or targeted synthetic DMARD following an initial TNFi.

BACKGROUND: Patients with rheumatoid arthritis, psoriasis, psoriatic arthritis, ankylosing spondylitis, Crohn's disease, or ulcerative colitis may require treatment with a biologic or targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD). Often, a tumor necrosis factor inhibitor (TNFi) is the initial b/tsDMARD. The TNFi may not be effective or may not be well tolerated, so patients will opt for a different TNFi or switch to a non-TNFi b/tsDMARD. No preference for a TNFi or non-TNFi has been established and guidelines are unclear. OBJECTIVE: To evaluate effectiveness by comparing patients using a second TNFi vs a non-TNFi after initial use of TNFi based on treatment patterns and health care utilization. METHODS: This retrospective analysis used Medicare Advantage prescription drug (MAPD) plan, Medicaid, and commercial plan claims data from Humana's Research Database (Louisville, KY). The first claim for TNFi or non-TNFi (July 1, 2016, to June 30, 2018) following earlier TNFi was the index date. Patients were required to have pre-index enrollment of 6 months and 12 months post-index along with diagnosis of rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn's disease, ulcerative colitis, or psoriasis. During the 12-month follow-up, persistence to the index TNFi or non-TNFi was measured as continued therapy without a gap exceeding 45 days (81 days for intravenous infusions). Adherence was proportion of days covered at least 0.8. Addition of a nonbiologic DMARD or corticosteroid was also identified. Inpatient admissions and emergency department visits were observed. Inverse probability of treatment weights was used to balance cohorts. Logistic regression models were fit to TNFi vs non-TNFI on treatment and utilization measures. RESULTS: Of identified patients, 1,022 were indexed to a second TNFi and 1,024 were indexed to non-TNFi. Weighted cohorts were balanced, with mean age 56.5 vs 56.4 years, 70.5% vs 70.7% female sex, and 68.0% vs 67.9% MAPD plan. No differences were observed on persistence or adherence, with adjusted odds ratios (OR) of 1.05 (95% CI = 0.91-1.20) and 1.04 (0.91-1.20), respectively. No differences were observed for changes in therapy via switching to another TNFi/non-TNFi (OR = 0.93; 95% CI = 0.54-1.62), via nonbiologic DMARD addition (OR = 0.95; 95% CI = 0.83-1.11), or corticosteroid addition (OR = 1.09; 95% CI = 0.92-1.88). No differences were observed for hospitalization (OR = 1.16; 95% CI = 0.99-1.37) or emergency department visits (OR = 1.02; 95% CI = 0.89-1.18). CONCLUSIONS: No differences were found between a second TNFi vs a non-TNFi. As a result, choice of TNFi or non-TNFi following an initial TNFi may be driven by relevant patient-specific considerations. At the population level, policies that prefer either TNFi or non-TNFi appear reasonable. DISCLOSURES: The study was funded by Humana Inc. Mr Racsa is an employee of Humana Healthcare Research, Inc., a subsidiary of Humana Inc. Drs Asante and Bloomfield are employees of Humana Inc. Dr Schwab was an employee of Humana Healthcare Research, Inc., a subsidiary of Humana Inc., and is now an employee of RTI Health Solutions. Dr Cornett was an employee of Humana Inc. and is now an employee of ImmunoGen Inc.

A multicenter, randomized, double-blind, phase III trial comparing denosumab biosimilar QL1206 and denosumab in patients with bone metastases from solid tumors.

2526 Background: This phase III study compared clinical efficacy, safety of the first biosimilar QL1206 with denosumab in solid tumor patients with bone metastases. Methods: Patients aged 18-80 years, with bone metastatic solid tumors and ECOG performance status of 0-2 were randomly assigned 1:1 to receive subcutaneous QL1206 or denosumab (120 mg Q4W, both) based on stratification factors (tumor types, previous skeletal-related event [SRE], and current systemic anti-tumor therapy). The primary efficacy endpoint was the percentage changes from baseline to week 13 in urinary N-telopeptide/creatinine ratio (uNTX/uCr); Clinical equivalence would be confirmed if the two-sided 90% confidence intervals (CI) of the least-squares mean (LSM) difference of natural log-transformed ratio of week 13 uNTX/uCr to baseline calculated by analysis of covariance were within the margins of ±0.135. The secondary endpoints included the percentage changes from baseline to week 25 and 53 in uNTX/uCr, the percentage changes from baseline to week 13, 25 and 53 in serum bone-specific alkaline phosphatase (s-BALP) and the time to on-study SRE. Adverse events (AE), immunogenicity (IG) and pharmacokinetics (PK) were also assessed. Population PK was analyzed using nonlinear mixed effects model. Results: 717 patients were randomized to the QL1206 (n = 357) and denosumab (n = 360) groups, respectively. The median percentage changes at week 13 in uNTX/uCr were -75.2% for QL1206 and -75.8% for denosumab. LSM of natural log-transformed ratio of week 13 uNTX/uCr to baseline were -1.429 (standard error 0.130) and -1.441 (0.130) in the two groups. The LSM difference between the two groups was 0.012 (90% CI -0.078 to 0.103; P = 0.8208), within the equivalence margins. Analyses for subgroups of sex, age, and randomization strata showed almost no significant differences. The secondary endpoints were also similar between the two groups (median percentage changes in s-BALP from baseline to week 13: -38.0% vs -37.1%; hazard ratio of time to SRE: 1.264 [95% CI 0.670 to 2.383]; both P > 0.05). In the safety set, treatment-emergent AE occurred in 332 of 356 patients (93.3%) in the QL1206 group and 348 of 361 (96.4%) in the denosumab group. The proportions of positive anti-drug antibody (14/345 [4.1%] vs 16/352 [4.5%]), neutralizing antibody (three [0.9%], each), and PK characteristics were similar between the two groups. Conclusions: The results suggest that QL1206, the first biosimilar denosumab, is similar to denosumab with respect to clinical efficacy, acceptable safety, IG, and PK characteristics. The totality of evidence supports clinical equivalence of QL1206 and denosumab. Clinical trial information: NCT04550949.

A Novel Immune Classification for Predicting Immunotherapy Responsiveness in Patients With Adamantinomatous Craniopharyngioma.

Adamantinomatous craniopharyngioma (ACP) is the most common tumor of the sellar region in children. The aggressive behavior of ACP challenges the treatment for it. However, immunotherapy is rarely studied in ACP. In this research, we performed unsupervised cluster analysis on the 725 immune-related genes and arrays of 39 patients with ACP patients in GSE60815 and GSE94349 databases. Two novel immune subtypes were identified, namely immune resistance (IR) subtype and immunogenic (IG) subtype. Interestingly, we found that the ACPs with IG subtype (34.78%, 8/23) were more likely to respond to immunotherapy than the ACPs with IR subtype (6.25%, 1/16) via tumor immune dysfunction and exclusion (TIDE) method. Simultaneously, the enrichment analysis indicated that the differentially expressed genes (DEGs) (p < 0.01, FDR < 0.01) of the IG subtype were chiefly involved in inflammatory and immune responses. However, the DEGs of the IR subtype were mainly involved in RNA processing. Next, immune infiltration analysis revealed a higher proportion of M2 macrophage in the IG subtype than that in the IR subtype. Compared with the IR subtype, the expression levels of immune checkpoint molecules (PD1, PDL1, PDL2, TIM3, CTLA4, Galectin9, LAG3, and CD86) were significantly upregulated in the IG subtype. The ssGSEA results demonstrated that the biofunction of carcinogenesis in the IG subtype was significantly enriched, such as lymphocyte infiltration, mesenchymal phenotype, stemness maintenance, and tumorigenic cytokines, compared with the IR subtype. Finally, a WDR89 (the DEG between IG and IR subtype)-based nomogram model was constructed to predict the immune classification of ACPs with excellent performance. This predictive model provided a reliable classification assessment tool for clinicians and aids treatment decision-making in the clinic.

Effect of donor-to-recipient HLA matching in low-immunological risk kidney transplant recipients without induction therapy on acute rejection, graft survival, infections, and surgical complications at 3 years: The road towards new recommendations

BackgroundDonor-to-recipient human leukocyte antigen mismatching is considered one of the strongest determinants for graft and patient survival in kidney transplant recipients (KTR). ObjectiveThis retrospective study discusses the impact of HLA matching as low immunological risk KTR without induction therapy. Material and methodsRecords of 80 adult kidney transplant patients were reviewed with three years of the follow-up. All patients had panel reactive antibodies (PRA) < 20%, absence of donor-specific antibodies (DSA) and did not receive the induction therapy. These patients were divided into two groups according to their HLA matching between donor and recipient: 55 patients with ≥ 3 HLA matches (Group I; low immunogenicity) were compared to 25 patients with <3 HLA matches (Group II; high immunogenicity). The primary endpoints included the rate and severity of acute rejection (AR) episodes, graft function (creatinine level), and survival at 1, 3, 6, 12, and 36 months. Secondary endpoints include the rate and type of infections at one-year, surgical complications at one-year, and patient survival at 1, 6, 12, and 36 months after kidney transplantation. Baseline demographic characteristics were comparable between the two groups except for recipient age, donor gender, and pre-transplant dialysis time. ResultsThere was no significant difference observed between two groups at one-year in infection rate, the length of hospital stay, AR severity, the rate of cytomegalovirus infection, and the occurrence of delayed graft function. However, the rate of AR, the graft function upon discharge, and the rate and type of surgical complications at one-year were significantly higher in Group II (high immunogenicity). The patient and graft survival at three years, the death-censored graft survival, and the serum creatinine levels at 1, 3, 6, 12, and 36 months were similar between two groups. Two deaths occurred in each group (NS). ConclusionIn our center, the donor-to-recipient HLA mismatch is not considered an immunological risk factor in low-risk kidney transplant recipients (PRA < 20% and absence of DSA).

The Role of Helicobacter pylori Proinflammatory Outer Membrane Protein and Propolis in Immunomodulation on U937 Macrophage Cell Model

Background: Regarding the important role of proinflammatory outer membrane protein (OipA) in the pathogenesis of Helicobacter pylori infection and immunomodulatory activity of propolis, we aimed to evaluate the immunogenicity effect of a purified recombinant OipA protein and propolis in the induction of two cytokines, interferon-gamma (IFN-γ) and interleukin-4 (IL-4), in a macrophage cell model. Materials and Methods: The recombinant protein used in the present study corresponding to the oipA expressing a 34-35 kDa protein. OipA protein was purified by Ni-NTA affinity chromatography. The purified OipA protein (2.5- 40 μg /mL) and the propolis ethanolic extract (5-40 μg/mL) were incubated with phorbol 12-myristate 13-acetate-treated human myelomonocytic cell line U937 cells. IL-4 and IFN-γ levels were measured after 48 hours of incubation using enzyme-linked immunosorbent assay. Results: The amounts of IL-4 and IFN-γ were significantly increased. The optimum concentration of OipA for the secretion of IL-4 was 5 μg/ml (P<0.0001). At higher concentrations, the amount of IL-4 diminished until suppression at 40 μg/mL. The optimum concentration of propolis, resulting in the most significant increased secretion of both IL-4 and IFN-γ was 40 μg/mL (P=0.0001 and P=0.0004). Conclusion: We found that an OipA concentration of 10 μg/mL was more effective for IFN-γ production; however, it was not effective for the high production of IL-4. Therefore, it is postulated that the OipA could mainly induce a Th1 response through the production of IFN-γ. We also observed propolis’s capability to induce IFN-γ production; however, the effective concentration for this was the same as for IL-4. Therefore, as an adjuvant, proper concentration of propolis is required for OipA to give the optimum response. [GMJ.2020;9:e1687]

Mesenchymal stem cells enable delivery of an oncolytic adenovirus specifically to the tumor without posing any risk associated with systemic administration of naked virions to the host

Background: Systemic delivery oncolytic virus to tumors remains a major challenge due to its poor tumor tropism and immuno genicity. Methods: In this regard, we hypothesize that mesenchymal stem cells (MSCs) with low immunogenicity and tumor-homing prop erty could serve as a promising systemic delivery tool for oncolytic viruses. Results: We showed that MSCs could be effectively infected by oncolytic adenovirus (oAd) and the virus replicated efficiently in the MSC carrier. Importantly, systemically administered oAd loaded in MSCs (oAd/MSC), which were initially infected with a low viral dose, led to significantly and preferentially elevated viral accumulation in tumor tissues, while attenuating virus detection in normal organs in respect to systemically administered naked oAd. Efficient retargeting of oAd to tumor tissues prevented the induction of oAd-associated hepatotoxicity that arise due to native hepatic tropism of systemically administered oAd. Further, pharmacokinetic profiling of oAd/MSC revealed that cell carrier improved and prolonged oAd retention in blood circulation com pared with naked Ad. Importantly, these attributes enabled oAd/MSC to elicit potent antitumor effect, while attenuating systemic toxicity. Conclusions: Collectively, these results demonstrate that MSC-mediated systemic delivery of oAd is a promising strategy for achieving synergistic antitumor efficacy with improved safety profiles.

Cloning, expression, purification and immunoassay of Tyr p 13 from Tyrophagus putrescentiae (Schrank)

Objective In this study, Tyrp 13 gene was cloned, the recombinant protein was expressed and purified, the immunological characteristics were identified, and the information of allergen epitope was analyzed by bioinformatics software. Methods The total RNA of the mite was extracted, RT-PCR was used to amplify the cDNA. The primers were designed according to the known Tyr p 13 gene sequence (GenBank Accession No. AY710432.1). A large number of target genes was amplified by PCR. Prokaryotic expression vector pet-32a (+) - Tyr p 13 was constructed, then transformed into E.coli Rosetta™ (DE3) Competent Cells, and the target protein expression was inducted by isopropyl β-d-1-thiogalactopyranoside (IPTG); purification of the expression product by chromatography, Western blot method was used to detect the immunological activity of the purified expression product; its antigen epitope was estimated by bioinformatics software, and its evolution tree was constructed. Results The length of the cloned DNA sequence was about 400 bp, and the expressed product was soluble in sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) with molecular weight of about 14 kD. Western blotting showed that Tyr p 13 could specifically bind to IgE in sera of allergic patients, which indicated that Tyr p 13 had allergenicity; epitope analysis further confirmed that the allergen had immunogenicity. Conclusion High purity Tyr p 13 can be obtained by clone expression and purification, which lays a theoretical foundation for further clinical specific diagnosis and treatment. 摘要：目的 克隆腐食酪螨第 13 组变应原基因 ( Tyr p 13 ) , 表达纯化其重组蛋白, 并进行免疫学特性鉴定, 利用生 物信息学软件分析该过敏原抗原表位等信息。 方法 挑取腐食酪螨, 提取螨总 RNA。逆转录-聚合酶链式反应 (RT- PCR) 扩增 cDNA, 根据已知的 Tyr p 13 基因序列 (GeneBank 登录号 AY710432.1) 设计引物, PCR 大量扩增目的基因。构 建原核表达载体 pET-32a (+) - Tyr p 13 , 转化感受态细胞 E. coli Rosetta (DE3) , 用 IPTG (异丙基-β-D-硫代半乳糖苷) 诱 导目的蛋白表达; 层析纯化表达产物, 免疫印迹 (Western Blot) 法检测纯化后的表达产物免疫学活性; 通过生物信息学 软件推测其抗原表位、构建进化树。 结果 克隆得到的序列经基因测序可知其长度约 400 bp, 其表达产物经十二烷基 硫酸钠-聚丙烯酰胺凝胶电泳 (SDS-PAGE) 分子量约为 14 kD, 呈可溶性表达。免疫印迹结果显示, Tyr p 13 能够与过敏 患者血清 IgE 特异性结合, 表明其具有过敏原性; 表位分析进一步证实该过敏原具有免疫原性。 结论 经克隆表达、纯 化后得到纯度较高的腐食酪螨 Tyr p 13 , 为进一步开展临床特异性诊断和治疗提供参考。

National expert consensus on the application of natural dermal matrix in wound repair (2020 version)

Natural dermal matrix has good biocompatibility and can serve as " biological template" in wound repair. According to the source of material, natural dermal matrix can be divided into acellular dermal matrix (ADM), denatured dermal matrix, and scar dermal matrix. ADM is a biological material prepared by removing cellular components from the skin and retaining extracellular matrix (ECM) of the dermis. ADM possesses abundant natural biological information, low immunogenicity, and excellent regenerative capacity, which has greatly promoted the development of wound healing specialty as dermal substitute. Denatured dermis matrix is a layer of dermal tissue made by superficial tangential excision or dermabrasion on deeply burned wounds. The retained denatured dermis can recover gradually after transplantation of autologous skin on its surface, with similar structure, morphology, and biomechanics to healthy dermis. Scar dermal matrix is a kind of dermal scaffold made of autologous split-thickness scar tissue, possessing the characteristics of high survival rate, good texture, and slight scar reaction. Scar dermal matrix can effectively reduce secondary damage to the donor site when repairing scar contracture deformity. Based on the research progress at home and abroad and the opinions of domestic experts, this paper summarizes the indications, application methods, contraindications, and considerations of different types of natural dermal matrix in application of wound repair.

Large scale Production of I-2 thermostable Newcastle Disease Vaccine in Sudan

In the present study, a live attenuated Newcastle Disease (ND) vaccine of I-2strain was produced locally. the master seed I-2 virus was first supplied by the Department of Veterinary Pathology of the University of Queensland, Australia, which then handed over by the Department of Veterinary Virology of the Central Veterinary Research Laboratory (CVRL) Sudan. A 11 days old embryonated chicken eggs with a minimal risk of vertical transmission were used for the virus propagation. The ND I-2 Master Seed Lot ( MSL) was prepared in aliquots and stored in a liquid form at -20⁰C. The Working Seed Lot (WSL) was prepared from the MSL and stored in a freeze dried form. The WSL then complied with the main quality tests of identity,safety, immunogenicity, efficacy, microbial contamination, thermostability and the infectivity titer tests.The virulence of the WSL was estimated via intracerepral pathogenicity index test (ICPI), the ICPI was 0.125 and the vaccine was proved to be safe in day old chicks.The immunogenicity measured by mean of ELISA. The GMT titer for the post vaccination serum was statistically significant than the pre vaccinated serum(P=0.001) paired sample t.test.The efficacy against a vvND virus, (ICPI 1.97) was 89% and the WSL was proved to be free from any detectable contaminant microorganisms. The temperature sensitivity for vaccine potency had been determined at different temperature levels and at Fluctuating Room Temperature (FRT). The titer decreased only by 0.2, 4.5 and 4.6 logs at temperatures -20⁰C, 37⁰C and 56⁰C respectively, while in the FRT decreased by 7.53 logs. The virus titer of WSL on the embryonated chickens, eggs was 9.1 EID50/ml.

Expression and purification of Brucella spp lumazine synthase decameric carrier in fusion to extracellular domain of influenza M2E protein

Brucella spp. Lumazine synthase enzyme, is a decameric protein carrier that display foreign antigens effectively in a polyvalent manner. The applied strategy using with this molecule results in a higher density of antigen and enhancing immunogenicity of peptide vaccines. In the current study, Brucella lumazine synthase (BLS) was applied for fusion with influenza matrix protein 2 ecto domain (M2E) as a foreign peptide. The primary studies were based on bioinformatics tools and the fusion was expressed and purified in following levels. Forming of decamer was confirmed by electrophoresis and western blotting techniques. Influenza matrix protein 2 was stably expressed at the 10 amino terminals of lumazine synthase. The purified fusion was injected to mice and immune responses were evaluated with indirect enzyme linked immunosorbent assay (ELISA) technique. According to ELISA results yield of purification process was 41% with ion exchange method and the protein was as a single band in Sodium Dodecyl Sulfate PolyAcrylamide Gel Electrophoresis (SDS-PAGE). The titer of immunized mice serum with decameric fusion of lumazine synthase and matrix protein (M2BL) was determined to be more than 1:32000 by indirect ELISA. The level of responses against matrix protein in decameric state of M2BL, was about 20% higher than monomer M2BL. Anti M2BL was cross reacted effectively with influenza M2E and in comparison with samples injected with adjuvant the level of antiM2E was similar. The results in this study confirms the role of multi copy presentation systems and applicability of BLS as an antigen carrier and adjuvant in designing peptide vaccines.

Tumor mutation burden associated with miRNA-gene interaction outcome mediates the survival of patients with liver hepatocellular carcinoma.

Tumor mutation burden (TMB) is associated with immunogenic responses and the survival of cancer patients. This study demonstrates how TMB levels impact the immune-related cells, genes, and miRNAs, and how miRNA/gene interactions respond to variations in the survival rate of patients with liver hepatocellular carcinoma (LIHC). LIHC patients were divided into two groups, either a low TMB (< median) or a high TMB (≥ median) group. We found that high TMB plays a positive role in immune-mediated infiltration, generating more CD4 T-cells and memory B cells. Among the 21 immune genes that altered significantly, only C9orf24 and CYP1A1 were expected to up-regulate in LIHC patients with high TMB. A total of 19 miRNAs, which regulate various functional pathways, were significantly altered in patients with LIHC. One of the miRNA/gene pair, hsa-miR-33a/ALDH1A3 was significantly associated with the survival rate of LIHC patients. Our results suggest that LIHC patients with high TMB can be treated more effectively with immunotherapy.

Safety and Immunogenicity of an Investigational Adenovirus Type-5–Vectored COVID-19 Vaccine

Development of a safe, effective COVID-19 vaccine is one of the most pressing current public health imperatives. Adenoviruses have been used safely as

Safety, Immunogenicity, and Efficacy of a Tetravalent Dengue Vaccine in Healthy Children

The tetravalent dengue vaccine TAK-003 (Takeda Vaccines, Inc.) is based on a live-attenuated dengue serotype-2 virus (DENV-2) that provides the genetic

Brolucizumab and immunogenicity.

Brolucizumab and immunogenicity.

Prokaryotic expression, purification and identification of the N protein of middle east respiratory syndrome coronavirus

Objective To express the N protein of middle east respiratory syndrome coronavirus （ MERS-CoV） in prokaryotic expression system and evaluate the immunogenicity of the purified recombinant N protein.Methods The gene encoding N protein of MERS-CoV was synthesized and cloned into the vector pET30a to construct the recombinant expression plasmid pET30a-MERS-CoV-N.The transformed E.coli BL21 （ DE3） strains carrying expression plasmid were induced by IPTG to express N protein.The expressed protein was purified by using affinity chromatography.SDS-PAGE and Western blot assays were used to iden-tify the expressed N protein and evaluate its immunogenicity.Results The recombinant N protein was suc-cessfully expressed in soluble form with the size of 46×103 .The results of Western blot assay showed that the recombinant N protein could specifically react with rabbit serum samples positive for antibodies against N protein B-cell epitope peptide and mouse anti-His tag antibodies.No positive band against N protein was found when primary antibody was used with thirty adult serum samples from Beijing in 2008.Conclusion N protein of MERS-CoV was successfully expressed in prokaryotic expression system.The successful expres-sion of N protein laid the foundation for immunological diagnosis of N protein of MERS-CoV and researches on its immunogenicity. Key words: Middle east respiratory syndrome coronavirus; N protein; Prokaryotic expression; Purification ; Identification

Immunological and Epidemiological Aspects of the Immunogenicity of Streptococcus Pneumoniae Serotype 3 Capsular Polysaccharide in Pneumococcal Vaccines

The introduction of pneumococcal vaccines into national immunization programmes around the world has reduced the incidence of pneumococcal vaccine serotypes, but had no influence on the incidence of Streptococcus pneumoniae serotype 3 included in their composition. The results of evaluation of epidemiological efficacy and immunogenicity of capsular polysaccharide of S. pneumoniae serotype 3 capsular polysaccharide (CP) in conjugated and polysaccharide pneumococcal vaccines are contradictory. Some studies have shown the effectiveness of vaccination, other studies indicate insufficient immunogenicity and prophylactic efficacy of S. pneumoniae serotype 3 CP. The authors’ analysis of the results of clinical studies showed that the prophylactic efficacy of S. pneumoniae serotype 3 CP depends on the type of vaccine, nosological form of the disease, age, immunization schedule. According to the literature data, the most informative parameter of the protective activity of S. pneumoniae CP in pneumococcal vaccines, including serotype 3, is opsonophagocytosis. The experimental data of the low immunogenicity of serotype 3 CP, presumably associated with an unusual way of synthesis of its CP, are considered. To increase the im muno genicity of S. pneumoniae serotype 3 CP, the use of synthetic oligosaccharides of a strictly defined chemical structure corresponding to the protective fragments of serotype 3 CP and conjugated with a carrier protein for induction of T-dependent immune response and immunological memory is promising.

Immunological and Epidemiological Aspects of the Immunogenicity of Streptococcus Pneumoniae Serotype 3 Capsular Polysaccharide in Pneumococcal Vaccines

The introduction of pneumococcal vaccines into national immunization programmes around the world has reduced the incidence of pneumococcal vaccine serotypes, but had no influence on the incidence of Streptococcus pneumoniae serotype 3 included in their composition. The results of evaluation of epidemiological efficacy and immunogenicity of capsular polysaccharide of S. pneumoniae serotype 3 capsular polysaccharide (CP) in conjugated and polysaccharide pneumococcal vaccines are contradictory. Some studies have shown the effectiveness of vaccination, other studies indicate insufficient immunogenicity and prophylactic efficacy of S. pneumoniae serotype 3 CP. The authors’ analysis of the results of clinical studies showed that the prophylactic efficacy of S. pneumoniae serotype 3 CP depends on the type of vaccine, nosological form of the disease, age, immunization schedule. According to the literature data, the most informative parameter of the protective activity of S. pneumoniae CP in pneumococcal vaccines, including serotype 3, is opsonophagocytosis. The experimental data of the low immunogenicity of serotype 3 CP, presumably associated with an unusual way of synthesis of its CP, are considered. To increase the im muno genicity of S. pneumoniae serotype 3 CP, the use of synthetic oligosaccharides of a strictly defined chemical structure corresponding to the protective fragments of serotype 3 CP and conjugated with a carrier protein for induction of T-dependent immune response and immunological memory is promising.

Immunogenicity of 2 Versus 3 Doses of Combined Hepatitis B Vaccines in 2-18 Months Old Children

Immunogenicity of 2 Versus 3 Doses of Combined Hepatitis B Vaccines in 2-18 Months Old Children

Research progress in exosomes delivery in the jaw regeneration

Large area defect of jaw caused by trauma, tumor resection, congenital malformation and periodontitis is a critial situation for oral and craniofacial reconstruction. Recent studies have shown that some exosomes carrying specific biological information play a role in promoting tissue regeneration. Compared to allogeneic stem-cell transplantation, exosomes have lower immunogenicity, and can facilitate storage and quantitative use, thus have great potential in tissue engineering. This article reviewed the regeneration process of jaw bone and the regulatory effect of exosomes transport on bone regeneration, as well as the research progress of exosomes in jaw bone-related diseases. Key words: Exosomes; Bone regeneration; Jaw; Bone marrow mesenchymal stem cells

Accelerated hepatitis B vaccination: Efficacy in young, regular blood donors

Background and Objectives: Hepatitis B (HB) – a vaccine-preventable, transfusion-transmitted infection – has been estimated to have high residual risk, especially in medium- and high-endemic areas. This potent immunogenic vaccine is routinely injected at 0, 1, and 6 months. Accelerated schedule has been recommended in adults to increase the completion rate. We studied the response rate of accelerated schedule in young, regular blood donors in a high-prevalence area for HB virus (HBV) in Iran. Methods: Young, regular nonimmunized blood donors were vaccinated with recombinant DNA HB surface antigen vaccine (Pasteur Institute of Iran) containing 20 μg of material in 1-ml solution injected intramuscularly to the deltoid muscle at 0, 1, and 2 months. HB surface antibody (HBsAb) was titered 1 month after the completion of doses. Nonresponders took one additional dose and tested a month later. Results: A total of 357 donors with a mean age of 26 ± 3.5 years were enrolled, of whom 287 donors completed three doses of vaccination (80% adherence rate). HBsAb titer was >10 IU/ml in 274 donors (95.5% response rate), whereas after one booster dose injection, the titer in 13 nonresponder persons (4.5%) increased to >10 IU/ml. Conclusion: Accelerated HBV vaccination with near 100% response rate and 80% adherence rate in young, regular blood donors has been successful in the immunization of young blood donors. This strategy improves not only blood safety but also donors' health.