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The conformational changes of poly(maleic anhydride-alt-styrene) (PSMA) modified with different amino acids (PSMA-Aa) were studied in an aqueous medium as a function of ionic strength and pH. The specific viscosity of PSMA-Aa decreased with increasing salt concentration due to a more compact conformation. There was a decrease in surface tension with increasing concentrations of the modified polyelectrolyte having a greater effect for the PSMA modified with l-phenylalanine at pH 7.0, demonstrating a greater surface-active character. The conformational changes were also confirmed by molecular dynamics studies, indicating that PSMA-Aa exhibits a compact structure at pH 4.0 and a more extended structure at pH 7.0. On the other hand, the conformational changes of PSMA-Aa were related to its biological response, where the higher surface-active character of the PSMA modified with l-phenylalanine correlates very well with the higher hemolytic activity observed in red blood cells, in which the surface-active capacity supports lytic potency in erythrocytes. The cytocompatibility assays indicated that there were no significant cytotoxic effects of the PSMA-Aa. Additionally, in solvent-accessible surface area studies, it was shown that the carboxylate groups of the PSMA modified with l-phenylalanine are more exposed to the solvent at pH 7.0 and high salt concentrations, which correlates with lower fluorescence intensity, reflecting a loss of mitochondrial membrane potential. It is concluded that the study of the conformational changes in PE modified with amino acids is essential for their use as biomaterials and relevant to understanding the possible effects of PE modified with amino acids in biological systems.

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Background: Accumulating evidence indicates that an early, robust type 1 interferon (IFN) response to SARS-CoV-2 is important in determining COVID-19 outcomes, with an inadequate IFN response associated with disease severity. Our objective was to examine the prophylactic potential of IFN administration to limit viral transmission. Methods: A cluster randomised open label clinical trial was undertaken to determine the effects of pegylated IFNß-1a administration on SARS-CoV-2 household transmission between December 3rd, 2020 and June 29th, 2021. Index cases were identified from databases of confirmed SARS-CoV-2 individuals in Santiago, Chile. Households were cluster randomised (stratified by household size and age of index cases) to receive 3 doses of 125 µg subcutaneous pegylated IFNß-1a (172 households, 607 participants), or standard care (169 households, 565 participants). The statistical team was blinded to treatment assignment until the analysis plan was finalised. Analyses were undertaken to determine effects of treatment on viral shedding and viral transmission. Safety analyses included incidence and severity of adverse events in all treatment eligible participants in the standard care arm, or in the treatment arm with at least one dose administered. Clinicaltrials.gov identifier: NCT04552379. Findings: 5154 index cases were assessed for eligibility, 1372 index cases invited to participate, and 341 index cases and their household contacts (n = 831) enrolled. 1172 participants in 341 households underwent randomisation, with 607 assigned to receive IFNß-1a and 565 to standard care. Based on intention to treat (ITT) and per protocol (PP) analyses for the primary endpoints, IFNß-1a treatment did not affect duration of viral shedding in index cases (absolute risk reduction = -0.2%, 95% CI = -8.46% to 8.06%) and transmission of SARS-CoV-2 to household contacts (absolute risk reduction = 3.87%, 95% CI = -3.6% to 11.3%). Treatment with IFNß-1a resulted in significantly more treatment-related adverse events, but no increase in overall adverse events or serious adverse events. Interpretation: Based upon the primary analyses, IFNß-1a treatment did not affect duration of viral shedding or the probability of SARS-CoV-2 transmission to uninfected contacts within a household. Funding: Biogen PTY Ltd. Supply of interferon as 'Plegridy (peginterferon beta-1a).' The study was substantially funded by BHP Holdings Pty Ltd.

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The ideal treatment for chronic wounds is based on the use of bioactive dressings capable of releasing active agents. However, the control of the rate at which these active agents are released is still a challenge. Bioactive polymeric fiber mats of poly(styrene-co-maleic anhydride) [PSMA] functionalized with amino acids of different hydropathic indices and L-glutamine, L-phenylalanine and L-tyrosine levels allowed obtaining derivatives of the copolymers named PSMA@Gln, PSMA@Phe and PSMA@Tyr, respectively, with the aim of modulating the wettability of the mats. The bioactive characteristics of mats were obtained by the incorporation of the active agents Calendula officinalis (Cal) and silver nanoparticles (AgNPs). A higher wettability for PSMA@Gln was observed, which is in accordance with the hydropathic index value of the amino acid. However, the release of AgNPs was higher for PSMA and more controlled for functionalized PSMA (PSMAf), while the release curves of Cal did not show behavior related to the wettability of the mats due to the apolar character of the active agent. Finally, the differences in the wettability of the mats also affected their bioactivity, which was evaluated in bacterial cultures of Staphylococcus aureus ATCC 25923 and methicillin-resistant Staphylococcus aureus ATCC 33592, an NIH/3T3 fibroblast cell line and red blood cells.

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BACKGROUND AND OBJECTIVES: Interferons have been identified as a potential treatment alternative for coronavirus disease 2019. This study assessed the safety, tolerability, bioavailability, and biological activity of inhaled interferon-α2b (IFN)-α2b in healthy adults. METHODS: A double-blind, randomized, phase I clinical trial was conducted with two cohorts of healthy subjects aged 18-50 years. The first cohort received 2.5 MIU of inhaled IFN-α2b twice daily for 10 days (n = 6) or placebo (n = 3); the second cohort received 5.0 MIU of inhaled IFN-α2b in a similar scheme (n = 6) or placebo (n = 3). The first two doses were administered in an emergency department, then participants completed their treatment at home. Safety was measured through vital signs, new symptoms, and laboratory tests. Tolerability was measured as participants' treatment acceptability. Bioavailability and biological activity were measured from serum IFNα concentrations and real-time quantitative polymerase chain reaction of interferon-induced genes in blood before and after treatments. RESULTS: Exposure to inhaled IFN-α2b at 2.5-MIU or 5-MIU doses did not produce statistically significant changes in participant vital signs, or elicit new symptoms, and standard hematological and biochemical blood measurements were comparable to those recorded in individuals who received placebo. A total of 58 adverse events were observed. All were mild or moderate and did not require medical care. All participants reported very high tolerability towards a twice-daily nebulized treatment for 10 days (98.0, 97.0, and 97.0 in the placebo, 2.5-MIU, and 5-MIU groups, respectively, on a 0- to 100-mm visual analog scale). A dose-dependent mild increase in serum IFN-α concentrations and an increase in serum RNA expression of IFN-induced genes were observed 11 days after treatment (p < 0.05 for all between-group comparisons). CONCLUSIONS: Inhaled IFN-α2b was preliminarily safe and well tolerated, and induced systemic biological activity in healthy subjects. CLINICAL TRIAL REGISTRATION: The trial was registered in ClinicalTrials.gov (NCT04988217), 3 August, 2021.

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BACKGROUND: The Omicron variant has challenged the control of the COVID-19 pandemic due to its immuno-evasive properties. The administration of a booster dose of a SARS-CoV-2 vaccine showed positive effects in the immunogenicity against SARS-CoV-2, effect that is even enhanced after the administration of a second booster. METHODS: During a phase-3 clinical trial, we evaluated the effect of a second booster of CoronaVac®, an inactivated vaccine administered 6 months after the first booster, in the neutralization of SARS-CoV-2 (n = 87). In parallel, cellular immunity (n = 45) was analyzed in stimulated peripheral mononuclear cells by flow cytometry and ELISPOT. FINDINGS: Although a 2.5-fold increase in neutralization of the ancestral SARS-CoV-2 was observed after the second booster when compared with prior its administration (Geometric mean units p < 0.0001; Geometric mean titer p = 0.0002), a poor neutralization against the Omicron variant was detected. Additionally, the activation of specific CD4+ T lymphocytes remained stable after the second booster and, importantly, equivalent activation of CD4+ T lymphocytes against the Omicron variant and the ancestral SARS-CoV-2 were found. INTERPRETATION: Although the neutralizing response against the Omicron variant after the second booster of CoronaVac® was slightly increased, these levels are far from those observed against the ancestral SARS-CoV-2 and could most likely fail to neutralize the virus. In contrast, a robust CD4+T cell response may confer protection against the Omicron variant. FUNDING: The Ministry of Health, Government of Chile, the Confederation of Production and Commerce, Chile and SINOVAC Biotech.NIHNIAID. The Millennium Institute on Immunology and Immunotherapy.

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Background: The development of vaccines to control the coronavirus disease 2019 (COVID-19) pandemic progression is a worldwide priority. CoronaVac is an inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine approved for emergency use with robust efficacy and immunogenicity data reported in trials in China, Brazil, Indonesia, Turkey, and Chile. Methods: This study is a randomized, multicenter, and controlled phase 3 trial in healthy Chilean adults aged ≥18 years. Volunteers received two doses of CoronaVac separated by 2 (0-14 schedule) or 4 weeks (0-28 schedule); 2302 volunteers were enrolled, 440 were part of the immunogenicity arm, and blood samples were obtained at different times. Samples from a single center are reported. Humoral immune responses were evaluated by measuring the neutralizing capacities of circulating antibodies. Cellular immune responses were assessed by ELISPOT and flow cytometry. Correlation matrixes were performed to evaluate correlations in the data measured. Results: Both schedules exhibited robust neutralizing capacities with the response induced by the 0-28 schedule being better. No differences were found in the concentration of antibodies against the virus and different variants of concern (VOCs) between schedules. Stimulation of peripheral blood mononuclear cells (PBMCs) with Mega pools of Peptides (MPs) induced the secretion of interferon (IFN)-γ and the expression of activation induced markers in CD4+ T cells for both schedules. Correlation matrixes showed strong correlations between neutralizing antibodies and IFN-γ secretion. Conclusions: Immunization with CoronaVac in Chilean adults promotes robust cellular and humoral immune responses. The 0-28 schedule induced a stronger humoral immune response than the 0-14 schedule. Funding: Ministry of Health, Government of Chile, Confederation of Production and Commerce & Millennium Institute on Immunology and Immunotherapy, Chile. Clinical trial number: NCT04651790.

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In this work, we report the obtaining of new hybrid nanocomposites with catalytic activity formed by nanofibers of polymer blends and gold nanoparticles. The nanofibers were obtained by electrospinning blends of a poly (ionic liquid) (PIL) and its precursor polymer, poly (4-vinyl pyridine) (P4VPy). The characteristics of the nanofibers obtained proved to be dependent on the proportion of polymer in the blends. The nanofibers obtained were used to synthesize, in situ, gold nanoparticles on their surface by two-step procedure. Firstly, the adsorption of precursor ions on the nanofibers and then their reduction with sodium borohydride to generate gold nanoparticles. The results indicated a significant improvement in the performance of PIL-containing nanofibers over pure P4VPy NFs during ion adsorption, reaching a 20% increase in the amount of adsorbed ions and a 6-fold increase in the respective adsorption constant. The catalytic performance of the obtained hybrid systems in the reduction reaction of 4-nitrophenol to 4-aminophenol was studied. Higher catalytic conversions were obtained using the hybrid nanofibers containing PIL and gold nanoparticles achieving a maximum conversion rate of 98%. Remarkably, the highest value of kinetic constant was obtained for the nanofibers with the highest PIL content.

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CoronaVac is an inactivated SARS-CoV-2 vaccine approved by the World Health Organization (WHO). Previous studies reported increased levels of neutralizing antibodies and specific T cells 2 and 4 weeks after two doses of CoronaVac; these levels were significantly reduced at 6 to 8 months after the two doses. Here, we report the effect of a booster dose of CoronaVac on the anti-SARS-CoV-2 immune response generated against the variants of concern (VOCs), Delta and Omicron, in adults participating in a phase III clinical trial in Chile. Volunteers immunized with two doses of CoronaVac in a 4-week interval received a booster dose of the same vaccine between 24 and 30 weeks after the second dose. Neutralization capacities and T cell activation against VOCs Delta and Omicron were assessed 4 weeks after the booster dose. We observed a significant increase in neutralizing antibodies 4 weeks after the booster dose. We also observed a rise in anti-SARS-CoV-2-specific CD4+ T cells over time, and these cells reached a peak 4 weeks after the booster dose. Furthermore, neutralizing antibodies and SARS-CoV-2-specific T cells induced by the booster showed activity against VOCs Delta and Omicron. Our results show that a booster dose of CoronaVac increases adults' humoral and cellular anti-SARS-CoV-2 immune responses. In addition, immunity induced by a booster dose of CoronaVac is active against VOCs, suggesting adequate protection. IMPORTANCE CoronaVac is an inactivated vaccine against SARS-CoV-2 that has been approved by WHO for emergency use. Phase III clinical trials are in progress in several countries, including China, Brazil, Turkey, and Chile, and have shown safety and immunogenicity after two doses of the vaccine. This report characterizes immune responses induced by two doses of CoronaVac followed by a booster dose 5 months after the second dose in healthy Chilean adults. The data reported here show that a booster dose increased the immune responses against SARS-CoV-2, enhancing levels of neutralizing antibodies against the ancestral strain and VOCs. Similarly, anti-SARS-CoV-2 CD4+ T cell responses were increased following the booster dose. In contrast, levels of gamma interferon secretion and T cell activation against the VOCs Delta and Omicron were not significantly different from those for the ancestral strain. Therefore, a third dose of CoronaVac in a homologous vaccination schedule improves its immunogenicity in healthy volunteers.

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Several vaccines have been developed to control the COVID-19 pandemic. CoronaVac®, an inactivated SARS-CoV-2 vaccine, has demonstrated safety and immunogenicity, preventing severe COVID-19 cases. We investigate the safety and non-inferiority of two immunization schedules of CoronaVac® in a non-inferiority trial in healthy adults. A total of 2302 healthy adults were enrolled at 8 centers in Chile and randomly assigned to two vaccination schedules, receiving two doses with either 14 or 28 days between each. The primary safety and efficacy endpoints were solicited adverse events (AEs) within 7 days of each dose, and comparing the number of cases of SARS-CoV-2 infection 14 days after the second dose between the schedules, respectively. The most frequent local AE was pain at the injection site, which was less frequent in participants aged ≥60 years. Other local AEs were reported in less than 5% of participants. The most frequent systemic AEs were headache, fatigue, and myalgia. Most AEs were mild and transient. There were no significant differences for local and systemic AEs between schedules. A total of 58 COVID-19 cases were confirmed, and all but 2 of them were mild. No differences were observed in the proportion of COVID-19 cases between schedules. CoronaVac® is safe, especially in ≥60-year-old participants. Both schedules protected against COVID-19 hospitalization.

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A wide variety of materials, strategies, and methods have been proposed to face the challenge of wastewater pollution. The most innovative and promising approaches include the hybrid materials made of polymeric nanofibers and photocatalytic nanoparticles. Electrospun nanofibers with unique properties, such as nanosized diameter, large specific surface area, and high aspect ratio, represent promising materials to support and stabilize photocatalytic nanosized semiconductors. Additionally, the role performed by polymer nanofibers can be extended even further since they can act as an active medium for the in situ synthesis of photocatalytic metal nanoparticles or contribute to pollutant adsorption, facilitating their approach to the photocatalytic sites and their subsequent photodegradation. In this paper, we review the state of the art of electrospun polymer/semiconductor hybrid nanofibers possessing photocatalytic activity and used for the remediation of polluted water by light-driven processes (i.e., based on photocatalytic activity). The crucial role of polymer nanofibers and their versatility in these types of procedures are emphasized.