Vaccines pave the way out of the SARS-CoV-2 pandemic. Besides mRNA and adenoviral vector vaccines, effective protein-based vaccines are needed for immunization against current and emerging variants... Show moreVaccines pave the way out of the SARS-CoV-2 pandemic. Besides mRNA and adenoviral vector vaccines, effective protein-based vaccines are needed for immunization against current and emerging variants. We have developed a virus-like particle (VLP)-based vaccine using the baculovirus-insect cell expression system, a robust production platform known for its scalability, low cost, and safety. Baculoviruses were constructed encoding SARS-CoV-2 spike proteins: full-length S, stabilized secreted S, or the S1 domain. Since subunit S only partially protected mice from SARS-CoV-2 challenge, we produced S1 for conjugation to bacteriophage AP205 VLP nanoparticles using tag/catcher technology. The S1 yield in an insect-cell bioreactor was similar to 11 mg/liter, and authentic protein folding, efficient glycosylation, partial trimerization, and ACE2 receptor binding was confirmed. Prime-boost immunization of mice with 0.5 mu g S1-VLPs showed potent neutralizing antibody responses against Wuhan and UK/B.1.1.7 SARS-CoV-2 variants. This two-component nanoparticle vaccine can now be further developed to help alleviate the burden of COVID-19.IMPORTANCE Vaccination is essential to reduce disease severity and limit the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Protein-based vaccines are useful to vaccinate the world population and to boost immunity against emerging variants. Their safety profiles, production costs, and vaccine storage temperatures are advantageous compared to mRNA and adenovirus vector vaccines. Here, we use the versatile and scalable baculovirus expression vector system to generate a two-component nanoparticle vaccine to induce potent neutralizing antibody responses against SARS-CoV-2 variants. These nanoparticle vaccines can be quickly adapted as boosters by simply updating the antigen component. Show less
Pijlman, J.; Holshof, G.; Berg, W. van den; Ros, G.H.; Erisman, J.W.; Eekeren, N. van 2020
Accurate estimates of the quantity and rate of soil nitrogen supply (SNS) are essential to increase soil and farm N use efficiencies, in particular for soils high in organic matter. The objective... Show moreAccurate estimates of the quantity and rate of soil nitrogen supply (SNS) are essential to increase soil and farm N use efficiencies, in particular for soils high in organic matter. The objective of this work was to enhance the empirical understanding of the SNS of dairy grasslands on peat soils, using soil properties and weather variables. Data were collected from studies on herbage N uptake carried out between 1992 and 2017 in the western peat district of the Netherlands. For the period between March to mid October, SNS was estimated from the sum of mean growing season daily temperatures, soil organic matter (SOM) and applied calcium ammonium nitrate (CAN) N with a residual standard error of 25-27 kg ha(-1). Each degrees C growing season temperature sum affected SNS by 78-90 g ha(-1) and each g SOM per 100 g dry soil affected SNS by 3.6-3.9 kg ha(-1), respectively. SNS was equally estimated for conditions with and without CAN fertilisation. Validation with data from independent field trials showed similar impacts of SOM and growing season temperature sum on SNS. The error of prediction of the presented models, however, was still too large for direct on-farm application and led to underestimations for a specific site. Nevertheless, the obtained models allow for an increased understanding of soil and farm N balances. The models can therefore be used for improved temporal and spatial SNS-adapted farming practice advice, which can potentially lead to reduced soil and farm N surpluses. Show less
Caam, A. van; Madej, W.; Thijssen, E.; Vinuesa, A.G. de; Berg, W. van den; Goumans, M.J.; ... ; Kraan, P.M. van der 2016
The development of novel treatments for rheumatoid arthritis (RA) requires the interplay between clinical observations and studies in animal models. Given the complex molecular pathogenesis and... Show moreThe development of novel treatments for rheumatoid arthritis (RA) requires the interplay between clinical observations and studies in animal models. Given the complex molecular pathogenesis and highly heterogeneous clinical picture of RA, there is an urgent need to dissect its multifactorial nature and to propose new strategies for preventive, early and curative treatments. Research on animal models has generated new knowledge on RA pathophysiology and aetiology and has provided highly successful paradigms for innovative drug development. Recent focus has shifted towards the discovery of novel biomarkers, with emphasis on presymptomatic and emerging stages of human RA, and towards addressing the pathophysiological mechanisms and subsequent effi cacy of interventions that underlie different disease variants. Shifts in the current paradigms underlying RA pathogenesis have also led to increased demand for new (including humanised) animal models. There is therefore an urgent need to integrate the knowledge on human and animal models with the ultimate goal of creating a comprehensive 'pathogenesis map' that will guide alignment of existing and new animal models to the subset of disease they mimic. This requires full and standardised characterisation of all models at the genotypic, phenotypic and biomarker level, exploiting recent technological developments in '-omics' profiling and computational biology as well as state of the art bioimaging. Efficient integration and dissemination of information and resources as well as outreach to the public will be necessary to manage the plethora of data accumulated and to increase community awareness and support for innovative animal model research in rheumatology. Show less
