HIV cure: global overview of bNAbs’ patents and related scientific publications

Introduction: This article provides a global overview of patent deposits for broadly neutralizing antibodies (bNAbs), which have emerged as a key strategy for HIV cure and future HIV vaccines. Scientific and technological barriers to the discovery of an effective HIV vaccine in the last 40 years have raised concerns on the potential for relevant advances in this area. Nevertheless, recent breakthrough studies have identified novel immune pathways for new innovative HIV vaccine and HIV cure strategies.

Areas covered: In our patent study, we have identified in a global scale, in the last decade, a sharp increase in the number of bNAbs’ patent deposits related to HIV prevention and treatment strategies, reaching 90 bNAbs in 2017, protected by 184 different patent deposits. Refining our patent search to the different stages of bNAbs’ development has also allowed us to identify 12 of them already at clinical stage of research (VRC01, 10E8, 3BNC117, 10-1074, 2G12, 2F5, KD-247, 4E10, PG9, PGDM1400, PGT121, and VRC07). We describe these recent breakthroughs and discuss the prospects and limitations of these novel strategies.

Expert opinion: Our results indicate the intellectual property outcomes of a scientific revolution in this field, expressing innovative modifications in antibodies to increase their potency and half-life, which have resulted in extremely potent antibodies that could provide novel preventive and therapeutic HIV strategies.     

The influence of C-factor, flexural modulus and viscous flow on gap formation in resin composite restorations

This study analyzed the influence of C-factor, flexural modulus and viscous flow on gap formation in resin composite restorations. Two resin composites, a mini-filled hybrid (P 60) and a nanofilled (Supreme), were used. The flexural modulus was obtained from bar-shaped specimens submitted to three-point bending. Viscous flow was obtained from the difference between the initial and final diameter of resin composite disks submitted to a load of 10 N for 120 seconds. Gap analysis was conducted in three types of cylindrical cavities (C-factor of 1.8, 2.6 and 3.4) that were prepared on the occlusal surfaces of human molars. The gap width at the dentin-resin composite interface was measured using a 3D scanning system (Talyscan 150). The data were analyzed by ANOVA and Student-Newman-Keuls' test, t-test and linear regression analysis (alpha = 0.05). The cavities with C-factor 3.4 presented the highest Gap formation (p < 0.0001). The lowest Gap formation was found in cavities restored with Supreme resin composite (p < 0.0001). P 60 presented significantly higher flexural modulus and lower viscous flow than Supreme (p < 0.0001). Regression analyses detected a significant influence of flexural modulus and viscous flow on gap formation (p < 0.05).     

On the Determination of Elastic Properties of Single-Walled Boron Nitride Nanotubes by Numerical Simulation

The elastic properties of chiral and non-chiral single-walled boron nitride nanotubes in a wide range of their chiral indices and diameters were studied. With this aim, a three-dimensional finite element model was used to assess their rigidities and, subsequently, elastic moduli and Poisson’s ratio. An extensive study was performed to understand the impact of the input parameters on the results obtained by numerical simulation. For comparison, the elastic properties of single-walled boron nitride nanotubes are shown together with those obtained for single-walled carbon nanotubes.     

Eleven novel mutations in the factor VIII gene from Brazilian hemophilia A patients

The molecular characterization of the mutations in hemophilia A patients is hampered by the large size of the factor VIII gene and the great heterogeneity of mutations. In this study, we have performed a protocol involving multiplex polymerase chain reaction in which 19 exons were amplified in four different combinations followed by nonradioactive single-strand conformational polymorphism (SSCP) to screen for mutations. Southern blotting was used to detect inversion of the factor VIII gene resulting from recombination between copies of the gene A (F8A) located in intron 22 of the factor VIII gene and two copies close telomeric region of X chromosome. Forty-two hemophilia A patients (21 with severe and 21 with mild-to-moderate disease) were studied. The inversion of factor VIII occurred in 13 of 21 patients affected by severe hemophilia A. One patient showed a large extra band in addition to the three bands observed after Southern blotting with the F8A probe. An abnormal electrophoretic pattern of SSCP was detected in 85% and 50% of the patients affected by mild-to-moderate and severe disease, respectively. Sixteen different mutations were identified. Eleven mutations were novel and comprised 9 point mutations and 2 small deletions. This study shows that the methodology used is safe and rapid and has potential for detecting almost all of the genetic defects of the studied hemophilia A patients.     

Effect of granulocyte inhibitory factor on granuloma formation in mice infected with Schistosoma mansoni

Mononuclear cells from patients infected with Schistosoma mansoni were able to produce a soluble material that inhibited the granulocyte cytotoxicity against schistosomula in a complement-dependent killing assay. This granulocyte inhibitory factor (GIF) appears to exist preformed in the mononuclear cells of patients, but it can also be released in the supernatant after antigenic stimulation (lymphokine-like). Only T lymphocytes were able to mediate the inhibition of granulocyte cytotoxicity against schistosomula in vitro. The treatment of S. mansoni-infected mice with GIF induced a significant decrease in the liver granuloma size.     

Analysis of Metal Contamination and Bioindicator Potential of Predatory Fish Species Along Contas River Basin in Northeastern Brazil

Samples of two carnivore fish species (Hoplias malabaricus and Serrasalmus brandtii) were collected along Contas River, northeastern Brazil, to determine the levels of Co, Cr, Cu, Fe, Mn, Ni and Pb in edible and non-edible tissues of these important local fisheries resources. Lead could not be quantified in most of the samples, while the other metals were detected in both species. In edible parts, Cr levels were above Brazilian threshold limits in all specimens and Ni was at high concentration in S. brandtii individuals from one collection site. In non-edible parts (viscera), besides Cr, Cu concentration was higher than that recommended by Brazilian laws. Both fish species proved to be sensitive to environmental contamination. Despite the different ecological characteristics, such as vagility and feeding strategy, these fish showed that aquatic predators are efficient bioindicators of water quality and biomagnification.