Tavares, D. | Search bioRxiv

bioRxiv2022

Cost-effectiveness of quadrivalent versus trivalent inactivated influenza vaccines for the Portuguese elderly population

BackgroundQuadrivalent Inactivated Vaccine (QIV) is expected to replace Trivalent Inactivated Vaccine (TIV) over time. In Portugal, TIV is free of charge for risk groups, which include older adults. In its turn, QIV - which provides broader protection as it includes an additional lineage B strain - was introduced in Portugal in October 2018, but only from the influenza season 2019/20 was provided free of charge for the risk groups. This study evaluates the cost-effectiveness of switching from TIV to QIV from the National Health Service perspective in the Portuguese elderly mainland population ([≥] 65 years old). MethodsA decision tree model was developed to compare TIV and QIV, based on Portuguese hospitalization data for the 2015/16 influenza season. The primary health economic outcome under consideration was the Incremental Cost-Effectiveness Ratio (ICER). In addition, a one-Way Sensitivity Analysis was performed to evaluate the impact of model parameters on the ICER; Probabilistic Sensitivity Analysis was also carried out to analyze the robustness of the base case results. ResultsThe high cost of QIV (approximately three times the cost of TIV) would lead to a total increment of 5,283,047 {euro}, and the resulting ICER would be 26,403,007{euro}/QALY, mainly above the usual willingness-to-pay threshold. ConclusionsFrom the National Health Service perspective, our findings reveal that QIV is not cost-effective for the Portuguese elderly population due to the high cost. If the QIV costs were the same as the TIV, then QIV would be cost-effective.

scientific communication and education↗

bioRxiv2019

Computational redesign of the Escherichia coli ribose-binding protein ligand binding pocket for 1,3-cyclohexanediol and cyclohexanol

Bacterial periplasmic-binding proteins have been acclaimed as general biosensing platform, but their range of natural ligands is too limited for optimal development of chemical compound detection. Computational redesign of the ligand-binding pocket of periplasmic-binding proteins may yield variants with new properties, but, despite earlier claims, genuine changes of specificity to non-natural ligands have so far not been achieved. In order to better understand the reasons of such limited success, we revisited here the Escherichia coli RbsB ribose-binding protein, aiming to achieve perceptible transition from ribose to structurally related chemical ligands 1,3-cyclohexanediol and cyclohexanol. Combinations of mutations were computationally predicted for nine residues in the RbsB binding pocket, then synthesized and tested in an E. coli reporter chassis. Two million variants were screened in a microcolony-in-bead fluorescence-assisted sorting procedure, which yielded six mutants no longer responsive to ribose but with 1.2-1.5 times induction in presence of 1 mM 1,3-cyclohexanediol, one of which responded to cyclohexanol as well. Isothermal microcalorimetry confirmed 1,3-cyclohexanediol binding, although only two mutant proteins were sufficiently stable upon purification. Circular dichroism spectroscopy indicated discernable structural differences between these two mutant proteins and wild-type RbsB. This and further quantification of periplasmic-space abundance suggested most mutants to be prone to misfolding and/or with defects in translocation compared to wild-type. Our results thus affirm that computational design and library screening can yield RbsB mutants with recognition of non-natural but structurally similar ligands. The inherent arisal of protein instability or misfolding concomitant with designed altered ligand-binding pockets should be overcome by new experimental strategies or by improved future protein design algorithms.

synthetic biology↗