Rare, convergent antibodies targeting the stem helix broadly neutralize diverse betacoronaviruses.

Humanity has faced three recent outbreaks of novel betacoronaviruses, emphasizing the need to develop approaches that broadly target coronaviruses. Here, we identify 55 monoclonal antibodies from COVID-19 convalescent donors that bind diverse betacoronavirus spike proteins. Most antibodies targeted an S2 epitope that included the K814 residue and were non-neutralizing. However, 11 antibodies targeting the stem helix neutralized betacoronaviruses from different lineages. Eight antibodies in this group, including the six broadest and most potent neutralizers, were encoded by IGHV1-46 and IGKV3-20. Crystal structures of three antibodies of this class at 1.5-1.75-Å resolution revealed a conserved mode of binding. COV89-22 neutralized SARS-CoV-2 variants of concern including Omicron BA.4/5 and limited disease in Syrian hamsters. Collectively, these findings identify a class of IGHV1-46/IGKV3-20 antibodies that broadly neutralize betacoronaviruses by targeting the stem helix but indicate these antibodies constitute a small fraction of the broadly reactive antibody response to betacoronaviruses after SARS-CoV-2 infection.

Broadly neutralizing antibodies target the coronavirus fusion peptide.

The potential for future coronavirus outbreaks highlights the need to broadly target this group of pathogens. We used an epitope-agnostic approach to identify six monoclonal antibodies that bind to spike proteins from all seven human-infecting coronaviruses. All six antibodies target the conserved fusion peptide region adjacent to the S2' cleavage site. COV44-62 and COV44-79 broadly neutralize alpha- and betacoronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariants BA.2 and BA.4/5, albeit with lower potency than receptor binding domain-specific antibodies. In crystal structures of COV44-62 and COV44-79 antigen-binding fragments with the SARS-CoV-2 fusion peptide, the fusion peptide epitope adopts a helical structure and includes the arginine residue at the S2' cleavage site. COV44-79 limited disease caused by SARS-CoV-2 in a Syrian hamster model. These findings highlight the fusion peptide as a candidate epitope for next-generation coronavirus vaccine development.

Broadly neutralizing antibodies target the coronavirus fusion peptide.

The potential for future coronavirus outbreaks highlights the need to develop strategies and tools to broadly target this group of pathogens. Here, using an epitope-agnostic approach, we identified six monoclonal antibodies that bound to spike proteins from all seven human-infecting coronaviruses. Epitope mapping revealed that all six antibodies target the conserved fusion peptide region adjacent to the S2' cleavage site. Two antibodies, COV44-62 and COV44-79, broadly neutralize a range of alpha and beta coronaviruses, including SARS-CoV-2 Omicron subvariants BA.1 and BA.2, albeit with lower potency than RBD-specific antibodies. In crystal structures of Fabs COV44-62 and COV44-79 with the SARS-CoV-2 fusion peptide, the fusion peptide epitope adopts a helical structure and includes the arginine at the S2' cleavage site. Importantly, COV44-79 limited disease caused by SARS-CoV-2 in a Syrian hamster model. These findings identify the fusion peptide as the target of the broadest neutralizing antibodies in an epitope-agnostic screen, highlighting this site as a candidate for next-generation coronavirus vaccine development. One-Sentence Summary: Rare monoclonal antibodies from COVID-19 convalescent individuals broadly neutralize coronaviruses by targeting the fusion peptide.

Uptake and Retention of Nanoplastics in Quagga Mussels.

Here, a set of experiments to assess the feasibility of using an invasive and widespread freshwater mussel (Dreissena rostrformis bugensis) as a sentinel species for nanoplastic detection is reported. Under laboratory experimental conditions, mussels ingest and retain fluorescent polystyrene (PS) beads with carboxylic acid (-COOH) termination over a size range of 200-2000 nm. The number of beads the mussels ingested is quantified using fluorescence spectroscopy and the location of the beads in the mussels is imaged using fluorescence microscopy. PS beads of similar size (1000-2000 nm) to mussels' preferred food are trafficked in the ciliated food grooves of the gills. Beads of all sizes are observed in the mussels' digestive tracts, indicating that the mussels do not efficiently reject the beads as unwanted foreign material, regardless of size. Fluorescence microscopy shows all sizes of beads are concentrated in the siphons and are retained there for longer than one month postexposure. Combined atomic force microscopy-infrared spectroscopy and photothermal infrared spectroscopy are used to locate, image, and chemically identify the beads in the mussel siphons. In sum, these experiments demonstrate the potential for using mussels, specifically their siphons, to monitor environmental accumulation of aquatic nanoplastics.

An investigation of the cost of food in the Geelong region of rural Victoria: Essential data to support planning to improve access to nutritious food.

ISSUE ADDRESSED: Affordability of a healthy diet is a determinant of nutritional intake and therefore health. This project aimed to measure the cost of healthy foods across a geographically defined region and examine factors related to changing food prices to assist in informing health promotion practice. METHODS: The cost of a healthy food basket was measured using the Victorian Healthy Food Basket tool, in all eligible stores, across five rural local government areas in Western Victoria, Australia in 2014, 2015 and 2016. One-way analysis of variance was used to investigate differences in healthy food basket cost across years. Multivariable linear regression models were constructed to adjust for baseline (2014) cost to determine factors associated with cost. RESULTS: Data were collected from 45 stores in 2014 and 2015 and 48 stores in 2016. The average cost of the healthy food basket was $459 in 2014, $437 in 2015 and $443 in 2016. The cost of the healthy food basket was the highest in stores >15 km from the major regional centre and in areas with only one supermarket (non-cluster) (P < 0.05). All food groups except fruit and vegetables decreased in price between 2014 and 2016. CONCLUSION: This project highlights distance from regional centres and competition as possible factors that influence the cost of healthy food. SO WHAT?: This is valuable insight for health promoters in designing both local level interventions aimed at improving access to healthy food and influencing regional food systems.