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Monoclonal antibodies (mAbs) are an important class of antiviral therapeutics. MAbs are highly selective, well tolerated, and have long in vivo half-life as well as the capacity to induce immune-mediated virus clearance. Their activities can be further enhanced by integration of their variable fragments (Fvs) into bispecific antibodies (bsAbs), affording simultaneous targeting of multiple epitopes to improve potency and breadth and/or to mitigate against viral escape by a single mutation. Here, we explore a bsAb strategy for generation of pan-ebolavirus and pan-filovirus immunotherapeutics. Filoviruses, including Ebola virus (EBOV), Sudan virus (SUDV), and Marburg virus (MARV), cause severe hemorrhagic fever. Although there are two FDA-approved mAb therapies for EBOV infection, these do not extend to other filoviruses. Here, we combine Fvs from broad ebolavirus mAbs to generate novel pan-ebolavirus bsAbs that are potently neutralizing, confer protection in mice, and are resistant to viral escape. Moreover, we combine Fvs from pan-ebolavirus mAbs with those of protective MARV mAbs to generate pan-filovirus protective bsAbs. These results provide guidelines for broad antiviral bsAb design and generate new immunotherapeutic candidates. Author summary: Filoviruses, such as Ebola virus and Marburg virus (EBOV and MARV, respectively), cause severe hemorrhagic fever with a high mortality rate in humans. Monoclonal antibodies (mAbs) are effective treatments for filovirus infection, but current therapies have limited breadth. Furthermore, a single mAb is susceptible to development of resistance. Here, we used protein engineering to create "bispecific" antibodies in which activities of two different mAbs were combined into one. These bispecific antibodies had broad activity, in one case providing protection against lethal challenge by two distant clades of filoviruses (EBOV and MARV). The bispecific antibodies were also less susceptible to resistance mutations. This work provides a roadmap for development of new bispecific antibody therapies for filoviruses. [ABSTRACT FROM AUTHOR]

The emergence of highly transmissible severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) that are resistant to the current COVID-19 vaccines highlights the need for continued development of broadly protective vaccines for the future. Here, we developed two messenger RNA (mRNA)-lipid nanoparticle (LNP) vaccines, TU88mCSA and ALCmCSA, using the ancestral SARS-CoV-2 spike sequence, optimized 5' and 3' untranslated regions (UTRs), and LNP combinations. Our data showed that these nanocomplexes effectively activate CD4+ and CD8+ T cell responses and humoral immune response and provide complete protection against WA1/2020, Omicron BA.1 and BQ.1 infection in hamsters. Critically, in Omicron BQ.1 challenge hamster models, TU88mCSA and ALCmCSA not only induced robust control of virus load in the lungs but also enhanced protective efficacy in the upper respiratory airways. Antigen-specific immune analysis in mice revealed that the observed cross-protection is associated with superior UTRs [Carboxylesterase 1d (Ces1d)/adaptor protein-3β (AP3B1)] and LNP formulations that elicit robust lung tissue-resident memory T cells. Strong protective effects of TU88mCSA or ALCmCSA against both WA1/2020 and VOCs suggest that this mRNA-LNP combination can be a broadly protective vaccine platform in which mRNA cargo uses the ancestral antigen sequence regardless of the antigenic drift. This approach could be rapidly adapted for clinical use and timely deployment of vaccines against emerging and reemerging VOCs. [ABSTRACT FROM AUTHOR]

Palladium nanoparticles stabilised by aniline modified polymer immobilised ionic liquid is a remarkably active catalyst for the hydrogenation of CO2 to formate; the initial TOF of 500 h−1 is markedly higher than either unmodified catalyst or its benzylamine and N,N-dimethylaniline modified counterparts and is among the highest to be reported for a PdNP-based catalyst. [ABSTRACT FROM AUTHOR]

The International Committee on Taxonomy of Viruses (ICTV) Filoviridae Study Group continues to prospectively refine the established nomenclature for taxa included in family Filoviridae in an effort to decrease confusion of genus, species, and virus names and to adhere to amended stipulations of the International Code of Virus Classification and Nomenclature (ICVCN). Recently, the genus names Ebolavirus and Marburgvirus were changed to Orthoebolavirus and Orthomarburgvirus, respectively. Additionally, all established species names in family Filoviridae now adhere to the ICTV-mandated binomial format. Virus names remain unchanged and valid. Here, we outline the revised taxonomy of family Filoviridae as approved by the ICTV in April 2023. [ABSTRACT FROM AUTHOR]

RuNPs stabilised by amino‐decorated imidazolium‐based polymer immobilized ionic liquids catalyse the dimethylamine borane mediated reduction of quinolines to 1,2‐dihydroquinoline (DHQ) and 1,2,3,4‐tetrahydroquinoline (THQ). Partial reduction of 3‐substituted quinolines to the corresponding 1,2‐dihydroquinoline was achieved with 100 % selectivity in toluene under mild conditions. This is the first report of the selective partial reduction of 3‐substituted quinolines to the corresponding 1,2‐dihydroquinolines with a heterogeneous nanoparticle‐based catalyst. A wide range of substituted quinolines have also been reduced to the corresponding 1,2,3,4‐tetrahydroquinoline with high selectivity and good yields by adjusting the reaction time. The 1,2‐dihydroquinolines readily release dihydrogen in toluene at 60 °C in the absence of catalyst with no evidence for disproportionation and as such are potential organo‐hydride reagents. The initial TOF of 610 mol quinoline converted mol Ru−1 h−1 for the reduction of quinoline is among the highest to be reported for a metal nanoparticle‐based catalyst and the conversion of 96 % obtained after 4 h at 65 °C is significantly higher than its platinum nanoparticle counterpart PtNP@NH2‐PEGPIILS as well as 5 wt/% Ru/C, which only reached 9 % and 11 % conversion, respectively, at the same time. Hot filtration experiments showed that the active species was heterogeneous. [ABSTRACT FROM AUTHOR]

Monoclonal antibody (mAb) therapies have rapidly become a powerful class of therapeutics with applications covering a diverse range of clinical indications. Though most widely used for the treatment of cancer, mAbs are also playing an increasing role in the defense of viral infections, most recently with palivizumab for prevention and treatment of severe RSV infections in neonatal and pediatric populations. In addition, during the COVID-19 pandemic, mAbs provided a bridge to the rollout of vaccines; however, their continued role as a therapeutic option for those at greatest risk of severe disease has become limited due to the emergence of neutralization resistant Omicron variants. Although there are many techniques for the identification of mAbs, including single B cell cloning and immunization of genetically engineered mice, the low cost, rapid throughput and technological simplicity of antibody phage display has led to its widespread adoption in mAb discovery efforts. Here we used our 27-billion-member naïve single-chain antibody (scFv) phage library to identify a panel of neutralizing anti-SARS-CoV-2 scFvs targeting diverse epitopes on the receptor binding domain (RBD). Although typically a routine process, we found that upon conversion to IgG, a number of our most potent clones failed to maintain their neutralization potency. Kinetic measurements confirmed similar affinity to the RBD; however, mechanistic studies provide evidence that the loss of neutralization is a result of structural limitations likely arising from initial choice of panning antigen. Thus this work highlights a risk of scFv-phage panning to mAb conversion and the importance of initial antigen selection. [ABSTRACT FROM AUTHOR]

[Display omitted] • Ultrafine RuNPs stabilised by a phosphine oxide-modified polymer immobilized ionic liquid. • Complete selectivity for the partial reduction of aromatic and heteroaromatic nitroarenes to the corresponding N -arylhydroxylamine. • Highest initial turn over frequency to be reported for a RuNP catalysed partial reduction of nitrobenzene to N -phenylhydroxylamine. • Reduction of electron rich amino nitroarenes to the aniline proposed to occur via a quinondiimine-derived iminium. • High activity and selectivity retained over five reuses with only a minor reduction in conversion. RuNPs stabilised by a polymer immobilised ionic liquid derived from co-polymerisation of a PEG-substituted imidazolium-based styrene monomer and diphenyl(4-vinylphenyl)phosphine oxide, RuNP@O = PPh 2 -PEGPIILS, (2) is a remarkably efficient and selective catalyst for the hydrazine hydrate-mediated partial reduction of nitroarenes to the corresponding N -arylhydoxylamine. Near quantitative conversion to N -phenylhydroxylamine with > 99 % selectivity was obtained after only 2 h when the reaction was conducted at 25 °C in ethanol under an inert atmosphere using 0.1 mol% catalyst. Under these conditions, the composition-time profile showed that the reduction occurred via the direct pathway whereas reactions in air gave a mixture of azoxy-based products due to competing condensation resulting from reversible formation of N -phenylhydroxylamine. The initial TOF of 6,100 h−1 obtained after 10 min at 40 °C with 0.1 mol% 2 is among the highest to be reported for the metal nanoparticle catalysed reduction of nitrobenzene to N -phenylhydroxylamine and a significant improvement on 5 wt% Ru/C which gave a modest conversion of 21 % (initial TOF = 240 h−1) to a mixture of N -phenylhydroxylamine and aniline. A broad range of substituted N -aryl and N -heteroaryl nitroarenes were reduced to the corresponding N -arylhydroxylamine in high yield and with excellent selectivity by adjusting the reaction times. However, reduction of electron rich amino-substituted nitroarenes was extremely slow and resulted in reduction to the aniline with no evidence for the corresponding hydroxylamine. Complete reduction of amino substituted nitroarene is proposed to be facilitated by amine-assisted elimination of hydroxide from the hydroxylamine to afford a readily reducible quinondiimine-derived iminium intermediate that reacts with a surface hydride to liberate the amine. Under optimum conditions the catalyst could be reused five times for the reduction of nitrobenzene to N -phenylhydroxylamine with no detectable change in activity and only slight decrease in selectivity. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) has had devastating effects worldwide, with particularly high morbidity and mortality in outbreaks on residential care facilities. Amantadine, originally licensed as an antiviral agent for therapy and prophylaxis against influenza A virus, has beneficial effects on patients with Parkinson's disease and is used for treatment of Parkinson's disease, multiple sclerosis, acquired brain injury, and various other neurological disorders. Recent observational data suggest an inverse relationship between the use of amantadine and COVID-19. Adamantanes, including amantadine and rimantadine, are reported to have in vitro activity against severe acute respiratory syndrome coronavirus (SARS-CoV) and, more recently, SARS-CoV-2. We hypothesized that adamantanes have antiviral activity against SARS-CoV-2, including variant strains. To assess the activity of adamantanes against SARS-CoV-2, we used in vitro and in vivo models of infection. We established that amantadine, rimantadine, and tromantadine inhibit the growth of SARS-CoV-2 in vitro in cultured human epithelial cells. While neither rimantadine nor amantadine reduces lung viral titers in mice infected with mouse-adapted SARS-CoV-2, rimantadine significantly reduces viral titers in the lungs in golden Syrian hamsters infected with SARS-CoV-2. In summary, rimantadine has antiviral activity against SARS-CoV-2 in human alveolar epithelial cells and in the hamster model of SARS-CoV-2 lung infection. The evaluation of amantadine or rimantadine in human randomized controlled trials can definitively address applications for the treatment or prevention of COVID-19. [ABSTRACT FROM AUTHOR]

The emergence of Marburg virus (MARV) in Guinea and Ghana triggered the assembly of the MARV vaccine "MARVAC" consortium representing leaders in the field of vaccine research and development aiming to facilitate a rapid response to this infectious disease threat. Here, we discuss current progress, challenges, and future directions for MARV vaccines. [ABSTRACT FROM AUTHOR]

Platinum and ruthenium nanoparticles stabilised by an amine modified polymer immobilised ionic liquid (MNP@NH2-PEGPIILS, M = Pt, Ru) catalyse the hydrolytic liberation of hydrogen from dimethylamine borane (DMAB), ammonia borane (AB) and NaBH4 under mild conditions. While RuNP@NH2-PEGPIILS and PtNP@NH2-PEGPIILS catalyse the hydrolytic evolution of hydrogen from NaBH4 with comparable initial TOFs of 6,250 molesH2.molcat−1.h−1 and 5,900 molesH2.molcat−1.h−1, respectively, based on the total metal content, RuNP@NH2-PEGPIILS is a markedly more efficient catalyst for the dehydrogenation of DMAB and AB than its platinum counterpart, as RuNP@NH2-PEGPIILS gave initial TOFs of 8,300 molesH2.molcat−1.h−1 and 21,200 molesH2.molcat−1.h−1, respectively, compared with 3,050 molesH2.molcat−1.h−1 and 8,500 molesH2.molcat−1.h−1, respectively, for PtNP@NH2-PEGPIILS. Gratifyingly, for each substrate tested RuNP@NH2-PEGPIILS and PtNP@NH2-PEGPIILS were markedly more active than commercial 5wt % Ru/C and 5wt% Pt/C, respectively. The apparent activation energies of 55.7 kJ mol−1 and 27.9 kJ mol−1 for the catalytic hydrolysis of DMAB and AB, respectively, with RuNP@NH2-PEGPIILS are significantly lower than the respective activation energies of 74.6 kJ mol−1 and 35.7 kJ mol−1 for its platinum counterpart, commensurate with the markedly higher initial rates obtained with the RuNPs. In comparison, the apparent activation energies of 44.1 kJ mol−1 and 46.5 kJ mol−1, for the hydrolysis NaBH4 reflect the similar initial TOFs obtained for both catalysts. The difference in apparent activation energies for the hydrolysis of DMAB compared with AB also reflect the higher rates of hydrolysis for the latter. Stability and reuse studies revealed that RuNP@NH2-PEGPIILS recycled efficiently as high conversions for the hydrolysis of DMAB were maintained across five runs with the catalyst retaining 97% of its activity.Graphical Abstract: Platinum and ruthenium nanoparticles stabilised by an amine modified polymer immobilised ionic liquid (MNP@NH2-PEGPIILS, M = Pt, Ru) catalyse the hydrolytic liberation of hydrogen from dimethylamine borane (DMAB), ammonia borane (AB) and NaBH4 under mild conditions. While RuNP@NH2-PEGPIILS and PtNP@NH2-PEGPIILS catalyse the hydrolytic evolution of hydrogen from NaBH4 with comparable initial TOFs of 6,250 molesH2.molcat−1.h−1 and 5,900 molesH2.molcat−1.h−1, respectively, based on the total metal content, RuNP@NH2-PEGPIILS is a markedly more efficient catalyst for the dehydrogenation of DMAB and AB than its platinum counterpart, as RuNP@NH2-PEGPIILS gave initial TOFs of 8,300 molesH2.molcat−1.h−1 and 21,200 molesH2.molcat−1.h−1, respectively, compared with 3,050 molesH2.molcat−1.h−1 and 8,500 molesH2.molcat−1.h−1, respectively, for PtNP@NH2-PEGPIILS. Gratifyingly, for each substrate tested RuNP@NH2-PEGPIILS and PtNP@NH2-PEGPIILS were markedly more active than commercial 5wt % Ru/C and 5wt% Pt/C, respectively. The apparent activation energies of 55.7 kJ mol−1 and 27.9 kJ mol−1 for the catalytic hydrolysis of DMAB and AB, respectively, with RuNP@NH2-PEGPIILS are significantly lower than the respective activation energies of 74.6 kJ mol−1 and 35.7 kJ mol−1 for its platinum counterpart, commensurate with the markedly higher initial rates obtained with the RuNPs. In comparison, the apparent activation energies of 44.1 kJ mol−1 and 46.5 kJ mol−1, for the hydrolysis NaBH4 reflect the similar initial TOFs obtained for both catalysts. The difference in apparent activation energies for the hydrolysis of DMAB compared with AB also reflect the higher rates of hydrolysis for the latter. Stability and reuse studies revealed that RuNP@NH2-PEGPIILS recycled efficiently as high conversions for the hydrolysis of DMAB were maintained across five runs with the catalyst retaining 97% of its activity. [ABSTRACT FROM AUTHOR]

Platinum nanoparticles stabilized by imidazolium‐based phosphine‐decorated Polymer Immobilized Ionic Liquids (PPh2‐PIIL) catalyze the hydrolytic evolution of hydrogen from sodium borohydride with remarkable efficiency, under mild conditions. The composition of the polymer influences efficiency with the catalyst based on a polyethylene glycol modified imidazolium monomer (PtNP@PPh2‐PEGPIILS) more active than its N‐alkylated counterpart (PtNP@PPh2‐N‐decylPIILS). The maximum initial TOF of 169 moleH2.molcat−1.min−1 obtained at 30 °C with a catalyst loading of 0.08 mol% is among the highest to be reported for the aqueous phase hydrolysis of sodium borohydride catalyzed by a PtNP‐based system. Kinetic studies revealed that the apparent activation energy (Ea) of 23.9 kJ mol−1 for the hydrolysis of NaBH4 catalyzed by PtNP@PPh2‐PEGPIILS is significantly lower than that of 35.6 kJ mol−1 for PtNP@PPh2‐N‐decylPIILS. Primary kinetic isotope effects kH/kD of 1.8 and 2.1 obtained with PtNP@PPh2‐PEGPIILS and PtNP@PPh2‐N‐decylPIILS, respectively, for the hydrolysis with D2O support a mechanism involving rate determining oxidative addition or σ‐bond metathesis of the O−H bond. Catalyst stability and reuse studies showed that PtNP@PPh2‐PEGPIILS retained 70 % of its activity across five runs; the gradual drop in conversion appears to be due to poisoning of the catalyst by the accumulated metaborate product as well as the increased viscosity of the reaction mixture. [ABSTRACT FROM AUTHOR]

Background: Convalescent plasma has been used to treat many viral diseases including Ebola. The manufacture of a purified anti-Ebola virus (EBOV) intravenous immunoglobulin (IVIG) from pooled convalescent plasma is described in this paper.Methods: An enzyme-linked immunosorbent assay (ELISA) targeting an EBOV surface glycoprotein antigen was used to determine the immunoglobulin titer of pooled plasma and purified anti-EBOV IVIG. Anti-EBOV IVIG was also tested in neutralization assays using a vesicular stomatitis virus pseudovirion expressing EBOV glycoprotein on its surface and with live EBOV. Finally, the efficacy of the anti-EBOV IVIG was assessed in a mouse model of EBOV infection.Results: In the ELISA, the anti-EBOV IVIG was shown to have a 7-fold increase in immunoglobulin G (IgG) titer over pooled convalescent plasma. In both the pseudovirion and live virus assays, the anti-EBOV IVIG showed approximately 5- to 6-fold increased potency over pooled plasma. Anti-EBOV IVIG also significantly improved survivability in mice infected with the virus when administered concurrently or 2 days after infection.Conclusions: These data support this purified anti-EBOV IVIG merits additional investigation and clinical trials for treatment and postexposure prophylaxis of Ebola virus disease. The experience gained can be applied to manufacture hyperimmune globulins against other emerging viruses. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has led to an unprecedented global health crisis, resulting in a critical need for effective vaccines that generate protective antibodies. Protein subunit vaccines represent a promising approach but often lack the immunogenicity required for strong immune stimulation. To overcome this challenge, it is first demonstrated that advanced biomaterials can be leveraged to boost the effectiveness of SARS‐CoV‐2 protein subunit vaccines. Additionally, it is reported that oxygen is a powerful immunological co‐adjuvant and has an ability to further potentiate vaccine potency. In preclinical studies, mice immunized with an oxygen‐generating coronavirus disease 2019 (COVID‐19) cryogel‐based vaccine (O2‐CryogelVAX) exhibit a robust Th1 and Th2 immune response, leading to a sustained production of highly effective neutralizing antibodies against the virus. Even with a single immunization, O2‐CryogelVAX achieves high antibody titers within 21 days, and both binding and neutralizing antibody levels are further increased after a second dose. Engineering a potent vaccine system that generates sufficient neutralizing antibodies after one dose is a preferred strategy amid vaccine shortage. The data suggest that this platform is a promising technology to reinforce vaccine‐driven immunostimulation and is applicable to current and emerging infectious diseases. [ABSTRACT FROM AUTHOR]

Ebola virus (EBOV), of the family Filoviridae, is an RNA virus that can cause a hemorrhagic fever with a high mortality rate. Defective viral genomes (DVGs) are truncated genomes that have been observed during multiple RNA virus infections, including in vitro EBOV infection, and have previously been associated with viral persistence and immunostimulatory activity. As DVGs have been detected in cells persistently infected with EBOV, we hypothesized that DVGs may also accumulate during viral replication in filovirus-infected hosts. Therefore, we interrogated sequence data from serum and tissue samples using a bioinformatics tool in order to identify the presence of DVGs in nonhuman primates (NHPs) infected with EBOV, Sudan virus (SUDV), or Marburg virus (MARV). Multiple 59 copy-back DVGs (cbDVGs) were detected in NHP serum during the acute phase of filovirus infection. While the relative abundance of total DVGs in most animals was low, serum collected during acute EBOV and SUDV infections, but not MARV infections, contained a higher proportion of short trailer sequence cbDVGs than the challenge stock. This indicated an accumulation of these DVGs throughout infection, potentially due to the preferential replication of short DVGs over the longer viral genome. Using reverse transcriptase PCR (RT-PCR) and deep sequencing, we also confirmed the presence of 59 cbDVGs in EBOV-infected NHP testes, which is of interest due to EBOV persistence in semen of male survivors of infection. This work suggests that DVGs play a role in EBOV infection in vivo and that further study will lead to a better understanding of EBOV pathogenesis. [ABSTRACT FROM AUTHOR]

Filoviruses (Family Filoviridae genera Ebolavirus and Marburgvirus) are negative-stranded RNA viruses that cause severe health effects in humans and non-human primates, including death. Except in outbreak settings, vaccines and other medical countermeasures against Ebola virus (EBOV) will require testing under the FDA Animal Rule. Multiple vaccine candidates have been evaluated using cynomolgus monkeys (CM) exposed to EBOV Kikwit strain. To the best of our knowledge, however, animal model development data supporting the use of CM in vaccine research have not been submitted to the FDA. This study describes a large CM database (122 CM, 62 female and 60 male, age 2 to 9 years) and demonstrates the consistency of the CM model through time to death models and descriptive statistics. CMs were exposed to EBOV doses of 0.1 to 100,000 PFU in 33 studies conducted at three Animal Biosafety Level 4 facilities, by three exposure routes. Time to death was modeled using Cox proportional hazards models with a frailty term that incorporated study-to-study variability. Despite significant differences attributed to exposure variables, all CMs exposed to the 100 to 1,000 pfu doses commonly used in vaccine studies died or met euthanasia criteria within 21 days of exposure, median 7 days, 93% between 5 and 12 days of exposure. Moderate clinical signs were observed 4 to 5 days after exposure and preceded death or euthanasia by approximately one day. Viremia was detected within a few days of infection. Hematology indices were indicative of viremia and the propensity for hemorrhage with progression of Ebola viremia. Changes associated with coagulation parameters and platelets were consistent with coagulation disruption. Changes in leukocyte profiles were indicative of an acute inflammatory response. Increased liver enzymes were observed shortly after exposure. Taken together, these factors suggest that the cynomolgus monkey is a reliable animal model for human disease. [ABSTRACT FROM AUTHOR]

The article discusses that recurrent antibody responses are driven by germline-encoded amino acid–binding (GRAB) motifs, a germline-encoded component of the architecture of the antibody repertoire that predisposes antibodies to recognize particular structures and influences epitope selection and composition. Public epitopes are best aligned for recognition by GRAB motifs and can be bound by a relatively large precursor pool of B cells.

• Ultrafine RuNPs are stabilised by amino-modified polymer immobilized ionic liquid. • High activity for hydrolytic evolution of hydrogen from NaBH 4. • Kinetic studies confirm the hydrolysis is first order in catalyst and hydride. • Kinetic isotope studies with H 2 O/D 2 O and NaBH 4 /NaBD 4 support the proposed mechanism. • High activity retained over five reuses with only a minor reduction in conversion. Ruthenium nanoparticles stabilised by polymer immobilized ionic liquids catalyse the hydrolytic release of hydrogen from sodium borohydride. The composition of the polymer influences performance and ruthenium nanoparticles stabilised by an amine-decorated imidazolium-based polymer immobilised ionic liquid (RuNP@NH 2 -PIILS) was the most efficient with a maximum initial turnover frequency (TOF) of 177 mole H2.mol Ru −1.min−1, obtained at 30°C with a catalyst loading of 0.08 mol%; markedly higher than that of 69 mol H2.mol Ru −1.min−1 obtained with 5 wt% Ru/C and one of the highest to be reported for a RuNP catalyst. The apparent activation energy (Ea) of 38.9 kJ mol−1 for the hydrolysis of NaBH 4 catalysed by RuNP@NH 2 -PIILS is lower than that for the other polymer immobilized ionic liquid stabilised RuNPs, which is consistent with its efficacy. Comparison of the initial rates of hydrolysis in H 2 O and D 2 O catalysed by RuNP@NH 2 -PIILS gave a primary kinetic isotope effect (k H / k D) of 2.3 which supports a mechanism involving rate limiting oxidative addition of one of the O-H bonds in a strongly hydrogen-bonded surface-coordinated [BH 3 H−]—-H 2 O ensemble. The involvement of a surface-coordinated borohydride is further supported by an inverse kinetic isotope effect of 0.65 obtained from a comparison of the initial rates for the hydrolysis of NaBH 4 and NaBD 4 under the conditions of catalysis i.e., at a high hydride/catalyst mole ratio. Interestingly though, when the comparison of the initial rates of hydrolysis of NaBH 4 and NaBD 4 was conducted in dilute solution with a hydride/catalyst mole ratio of 1 a kinetic isotope effect (k H / k D) of 2.72 was obtained; this would be more consistent with concerted activation of both an O-H and B-H bond in the rate limiting step, possibly via a concerted oxidative addition-hydride transfer in the surface-coordinated hydrogen-bonded ensemble. Catalyst stability and reuse studies showed that RuNP@NH 2 -PIILS retained 71% of its activity over five runs; the gradual drop in the initial TOF with run number appears to be due to passivation of the catalyst by the sodium borate by-product as well as an increase in viscosity of the reaction mixture rather than leaching of the catalyst. [Display omitted] [ABSTRACT FROM AUTHOR]

Biomaterials and Oxygen Join Forces to Shape the Immune Response and Boost COVID-19 Vaccines (Adv. Sci. 18/2021) B COVID-19 Vaccines b In article number 2100316 by Sidi A. Bencherif and co-workers, it is demonstrated that advanced biomaterials can be leveraged to boost the effectiveness of SARS-CoV-2 protein subunit vaccines. Illustration depicting a subcutaneously injected oxygen-releasing cryogel-based COVID-19 vaccine boosting the immune response, leading to a sustained production of highly effective neutralizing antibodies against SARS-CoV-2. [Extracted from the article]