3D Printing of PDMS-Like Polymer Nanocomposites with Enhanced Thermal Conductivity: Boron Nitride Based Photocuring System

This study demonstrates the possibility of forming 3D structures with enhanced thermal conductivity (k) by vat printing a silicone–acrylate based nanocomposite. Polydimethylsiloxane (PDSM) represent a common silicone-based polymer used in several applications from electronics to microfluidics. Unfortunately, the k value of the polymer is low, so a composite is required to be formed in order to increase its thermal conductivity. Several types of fillers are available to reach this result. In this study, boron nitride (BN) nanoparticles were used to increase the thermal conductivity of a PDMS-like photocurable matrix. A digital light processing (DLP) system was employed to form complex structures. The viscosity of the formulation was firstly investigated; photorheology and attenuate total reflection Fourier-transform infrared spectroscopy (ATR-FTIR) analyses were done to check the reactivity of the system that resulted as suitable for DLP printing. Mechanical and thermal analyses were performed on printed samples through dynamic mechanical thermal analysis (DMTA) and tensile tests, revealing a positive effect of the BN nanoparticles. Morphological characterization was performed by scanning electron microscopy (SEM). Finally, thermal analysis demonstrated that the thermal conductivity of the material was improved, maintaining the possibility of producing 3D printable formulations

Long-term immunogenicity and safety of a non-typeable Haemophilus influenzae-Moraxella catarrhalis vaccine : 4-year follow-up of a phase 1 multicentre trial

A multicomponent vaccine has been developed to reduce the frequency of acute exacerbations of COPD associated with non-typeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis (Mcat) infections, containing NTHi (PD and PE-PilA) and Mcat (UspA2) surface proteins. In a randomised, observer-blind, placebo-controlled study with two steps (NCT02547974), the investigational vaccine had good immunogenicity and no safety concerns were identified. In step 2, 90 adults aged 50-71 years with smoking history received two doses 60 days apart of one of two AS01(E)-adjuvanted formulations containing 10 mg of each antigen (10-10-AS01) or 10 mu g NTHi antigens and 3.3 mu g UspA2 (10-3-AS01), or placebo. Long-term persistence of antigen-specific humoral antibodies was assessed in 81 participants during 3 years of follow-up after the initial 14-month study (NCT03201211). Antigen-specific antibody concentrations were measured in blood samples taken every 6 months. Safety monitoring evaluated serious adverse events (SAEs) and potential immune-mediated disease (pIMD). Immune responses against NTHi antigens persisted up to 4 years post-vaccination. For PD, PE and PilA, at each follow-up time point, adjusted antibody geometric mean concentrations (GMCs) were higher (non-overlapping 95% confidence intervals [CIs]) in the vaccine groups versus placebo and versus prevaccination. Antibody GMC point estimates were higher with 10-3-AS01 than with 10-10-AS01. For UspA2, 95% CIs included 1 for GMC ratios of 10-10-AS01 or 10-3-AS01 to placebo at each time point. During follow-up, SAEs were reported in nine (11.1%) participants, one of which was fatal (lung cancer, 607 days after second 10-10-AS01 dose). One non-serious pIMD, trigeminal neuralgia, was reported 771 days after second 10-3-AS01 dose. The SAEs and pIMD were considered not related to vaccination. Immune responses against NTHi antigens persisted for 4 years after two-dose vaccination with the investigational NTHi-Mcat vaccine. There was no persistent response against the Mcat antigen. No safety concerns were identified during the long-term follow-up. (C) 2021 GlaxoSmithKline Biologicals S.A. Published by Elsevier Ltd

A Phase 2a Randomized Study to Evaluate the Safety and Immunogenicity of the 1790GAHB Generalized Modules for Membrane Antigen Vaccine against Shigella sonnei Administered Intramuscularly to Adults from a Shigellosis-Endemic Country

Shigellosis is a mild-to-severe diarrheal infection, caused by the genus Shigella, and is responsible for significant morbidity and mortality worldwide. We evaluated the safety and immunogenicity of an investigational Shigella sonnei vaccine (1790GAHB) based on generalized modules for membrane antigens (GMMA) in Kenya, a Shigella-endemic country. This phase 2a, observer-blind, controlled randomized study (NCT02676895) enrolled 74 healthy adults aged 18–45 years, of whom 72 were vaccinated. Participants received, in a 1:1:1 ratio, two vaccinations with the 1790GAHB vaccine at doses of either 1.5/25 μg of O antigen (OAg)/protein (group 1.5/25 μg) or 5.9/100 μg (group 5.9/100 μg) at day (D) 1 and D29, or vaccination with a quadrivalent meningococcal vaccine at D1 and tetanus, diphtheria, and acellular pertussis vaccine at D29 (control group). Solicited and unsolicited adverse events (AEs), serious AEs (SAEs), and AEs of special interest (neutropenia and reactive arthritis) were collected. Anti-S. sonnei lipopolysaccharide (LPS) serum immunoglobulin G (IgG) geometric mean concentrations (GMC) were evaluated at D1, D29, and D57 and compared to anti-S. sonnei LPS antibody levels in convalescent patients naturally exposed to S. sonnei. The percentages of participants with seroresponse were also calculated. The most frequently reported solicited local and systemic AEs across all groups were pain and headache, respectively. Only one case of severe systemic reaction was reported (severe headache after first vaccination in group 5.9/100 μg). Seven and three episodes of neutropenia, assessed as probably or possibly related to vaccination respectively, were reported in the investigational and control groups, respectively. No other SAEs were reported. Despite very high baseline anti-S. sonnei LPS serum IgG levels, the 1790GAHB vaccine induced robust antibody responses. At D29, GMC increased 2.10- and 4.43-fold from baseline in groups 1.5/25 and 5.9/100 μg, respectively, whereas no increase was observed in the control group. Antibody titers at D57 were not statistically different from those at D29. Seroresponse was 68% at D29 and 90% at D57 in group 1.5/25 μg, and 96% after each vaccination in group 5.9/100 μg. The 1790GAHB vaccine was well tolerated and highly immunogenic in a population of African adults, regardless of the GMMA OAg/protein content used