Histogen (United States)

Abstract How human genetic variation contributes to vaccine immunogenicity and effectiveness is unclear, particularly in infants from Africa. We undertook genome-wide association analyses of eight vaccine antibody responses in 2,499 infants from three African countries and identified significant associations across the human leukocyte antigen (HLA) locus for five antigens spanning pertussis, diphtheria and hepatitis B vaccines. Using high-resolution HLA typing in 1,706 individuals from 11 African populations we constructed a continental imputation resource to fine-map signals of association across the class II HLA observing genetic variation explaining up to 10% of the observed variance in antibody responses. Using follicular helper T-cell assays,in silicobinding, and immune cell eQTL datasets we find evidence ofHLA-DRB1expression correlating with serological response and inferred protection from pertussis following vaccination. This work improves our understanding of molecular mechanisms underlying HLA associations that should support vaccine design and development across Africa with wider global relevance.TeaserHigh-resolution typing of HLA diversity provides mechanistic insights into differential potency and inferred effectiveness of vaccines across Africa.

A nucleotide mutation in codon 75 of HLA-C*04:01:01:01 results in a novel allele HLA-C*04:279N.

Introduction: Induction of in vitro spermatogenesis can be useful for infertility treatment in azoospermic patients and those undergoing chemotherapy. Different culture systems have been used to achieve this goal. This review study was performed with the aim to evaluate the application of 3D culture and testicular scaffolds in the establishment of in vitro spermatogenesis. In this review study, the information on the application of 3D culture and testicular scaffolds in induction of in vitro spermatogenesis was searched in databases such as SID, Magiran, PubMed, Irandoc, Iranmedx Scopus, Google Scholar, Web of Science using the keywords of three dimensional culture, testicular scaffold, spermatogenesis, spermatogonial stem cells without time limitation. Data analysis was carried out qualitatively. Finally, 35 papers in English and Persian were used to compile the article. In order to induce of in vitro spermatogenesis, three-dimensional culture methods such as testicular tissue culture, soft agar culture system, natural biomaterial scaffolds such as collagen, and scaffolds derived from decellularized testis have been used. Conclusion: Three-dimensional culture using spermatogonial stem cells and scaffolds can be used in vitro for induction of spermatogenesis, but there are further technical and ethical challenges in the path of fertile sperm production for the treatment of infertility.

Autologous monocyte-derived mRNA co-electroporated dendritic cells with mRNA encoding CD40 ligand (CD40L), CD70 and a constitutively activated TLR4 (caTLR4) (referred to as TriMixDC-MEL) have anti-tumor activity in advanced melanoma patients. We investigated the safety and activity of adjuvant TriMixDC-MEL in stage III/IV melanoma patients. Forty-one patients were randomly assigned to treatment with TriMixDC-MEL (n = 21) and standard follow-up (n = 20). "Cross-over" was allowed at the time of non-salvageable recurrence. The primary endpoint was the percentage of patients alive and disease-free at 1-year. For a subset of patients, (formalin-fixed paraffin-embedded), tumor tissue samples were available for mRNA expression profiling and PD-L1 immunohistochemical staining. Baseline characteristics were well balanced. One-year after randomization, 71% of patients in the study arm were alive and free of disease compared to 35% in the control arm. After a median follow-up of 53months (range 3-67), 23 patients experienced a non-salvageable melanoma recurrence (TriMixDC-Mel arm n = 9 and control arm n = 14).The median time to non-salvageable recurrence was superior in the TriMixDC-MEL arm (median 8months (range 1-6) vs. not reached; log-rank p 0.044). TriMixDC-MEL-related adverse events (AE) consisted of transient local skin reactions, flu-like symptoms and post-infusion chills. No grade ≥ 3 AE's occurred. The mRNA expression profiling revealed four genes (STAT2, TPSAB1, CD9 and CSF2) as potential predictive biomarkers. TriMixDC-MEL id/iv as adjuvant therapy is tolerable and may improve the 1-year disease-free survival rate. Combination of optimized autologous monocyte-derived DC-formulations warrants further investigation in combination with currently approved adjuvant therapy options.

One nucleotide substitution in codon 38 of HLA-DQB1*06:01:01:01 results in a novel allele, HLA-DQB1*06:132.

Three new HLA-C alleles were identified by sequence-based typing method (SBT) in donors for the Saudi Bone Marrow Donor Registry (SBMDR). HLA-C*14:02:13 differs from HLA-C*14:02:01 by a silent G to A substitution at nucleotide position 400 in exon 2, where lysine at position 66 remains unchanged. HLA-C*15:72 differs from HLA-C*15:22 by a nonsynonymous C to A substitution at nucleotide position 796 in exon 3, resulting in an amino acid change from phenylalanine to leucine at position 116. HLA-C*15:74 differs from HLA-C*15:08 by a nonsynonymous C to T substitution at nucleotide position 914 in exon 3, resulting in an amino acid change from arginine to tryptophan at position 156.

Abstract We have previously shown that a human soluble cell conditioned media (CCM) from hypoxia-induced, potentially multipotent cells, grown in a perfusion bioreactor system inhibits tumor cell growth in vitro and in two animal models. Here we present data that indicate that a low molecular weight sub-fraction from the CCM has an increased anti-oncogenic activity. This activity was demonstrated in orthotopic pancreatic models, nRAS melanoma assays and over 10 additional human cancer cell lines in vitro. In an orthotopic BxPC3 pancreatic cancer model, there was a statistically significant improvement in survival following weekly intravenous injections of 0.1ml of sub fractioned CCM, as well as a significant improvement with 0.5ml intraperitoneal injections post-resection, as measured by Kaplan Meier analysis (p<0.05) (figures below). Uveal and nRAS melanoma cancer cell growth was inhibited by greater than 90% in in-vitro proliferation assays. The mechanism of action of the CCM is the induction of apoptosis through the upregulation of Caspase 3 and 9, as demonstrated by immunostaining of Annexin V and immunoblot ayalysis. In a Miapaca nude mouse daily dose study, tumor mass and metastatic extent was substantially reduced in treated mouse versus the control. Further, in a BXPC3 nude mouse daily dose study, 60% (p<0.05) of treated mice were tumor free after four weeks of treatment, while only 10% were tumor free in the control group . Little or no apparent drug toxicity was observed. These results indicate that the CCM sub-fraction could be a useful raw material for a treatment for a large range of neoplastic diseases. Citation Format: Emmett Pinney, Mayra Montes-Camacho, Kayler Brintle, Christian Posch, Rhiana Menen, David Easter, Michael Bouvet, Robert Hoffman, Gail Naughton. Sub-fractions of conditioned medium, from hypoxia-induced cells with multipotent potential, exhibit a significant anti-oncogenic activity. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2265. doi:10.1158/1538-7445.AM2014-2265

In this report, we present two novel HLA-A alleles: HLA-A*02:433 and HLA-A*02:434. These alleles were identified by sequence-based typing method (SBT), in two donors for the Saudi Bone Marrow Donor Registry (SBMDR). Allele A*02:433 is identical to A*02:05:01G except for a G to A substitution at nucleotide position 449 in exon 2. This substitution results in glycine to serine substitution at position 83. Whereas, allele A*02:434 is identical to A*02:01:01G except for a C to A substitution at nucleotide position 245 in exon 2, which results in phenylalanine to threonine substitution at position 15. The generation of both alleles appears to be the result of nucleotide point mutation involving 02:01:01 and 02:05:01.