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To enable a sensed RNA to activate diverse RNA effectors, the authors engineer a programmable dual-site ribozyme that, upon RNA trigger binding, self-cleaves to release an embedded RNA. It enables trigger-dependent release of diverse ncRNAs and controls CRISPR-Cas9 editing in zebrafish and human cells.

SARS-CoV-2 has been shown to induce IL-1β-mediated neuroinflammation in humans and rodent models. Klein and colleagues show that low-dose COVID-19 vaccination prevents breakthrough infection-mediated hippocampal dysfunction and cognitive memory decline in mouse models.

Identification of clinical relevant biomarkers to predict response to immune checkpoint blockade (ICB) in melanoma remains challenging. Here, the authors show that stroma remodelling and reduced cell division are associated with durable response to anti-PD1 in a mouse model of melanoma and in ICB-treated patients.

A comprehensive analysis of antibody neutralization activity against a panel of authentic isolates and chimeric SARS-CoV-2 variants shows markedly diminished neutralizing activity against the variant B.1.351, first identified in South Africa.

Here, the authors enhance their nasally delivered chimpanzee adenoviral-vectored SARS-CoV-2 vaccine with an Omicron-matched vaccine (ChAd-SARS-CoV-2-BA.5-S) that stimulates mucosal immunity in mice and hamsters and shows cross-reactive CD8⁺ memory T cell-driven protection against antigenically distant strains.

Influenza A virus packaging depends on interactions between nucleoprotein (NP) and viral RNA (vRNA), but the pattern of NP binding is unclear. Using PAR-CLIP, Williams et al. here show that NP binds vRNA non-uniformly and that RNA structures in low-NP binding regions are important for packaging.

Sensing of cytosolic RNA or DNA can lead to innate responses, but little information is available for RNA/DNA dual sensors. Here the authors find SAMD9 as a potential dual sensor linked to pro-inflammatory responses, interferon induction and resistance to viral infection, as evidenced by in vitro overexpression and in vivo knockout mouse data.

Here, the authors develop a chronic murine model of Acinetobacter baumannii pulmonary infection that overcomes some limitations of acute models and allows investigation of virulence factors, long-term antibiotic treatment, and polymicrobial infections.

7DW8-5 is a glycolipid that binds CD1d and stimulates invariant natural killer T (iNKT) cells. Here the authors show that 7DW8-5, when administered intranasally, provides prophylactic anti-viral effects against influenza, RSV, and SARS-CoV-2 in mice or hamsters, and that this effect is mediated by iNKT cells and IFN-γ.

Experiments in mouse and hamster models show that monoclonal antibody combinations, using antibodies that correspond to products in clinical development, largely retain their efficacy in protecting against currently prevailing variant strains of SARS-CoV-2.

A collaborative study demonstrates that, compared with previous SARS-CoV-2 variants, B.1.1.529 isolates cause less infection and disease in mice and hamsters, in agreement with preliminary data from studies in humans.

Noise, is familiar from communications, where a single parameter such as voltage varies with time. Usually it is a nuisance, but sometimes, because of the peculiar phenomenon known as stochastic resonance, it is a boon, increasing signal strength. Noise is also present in many extended natural phenomena, such as calcium-ion waves in the brain. Are there also extended systems in which the noise can increase some collective, or coherent, dynamical property? Such spatiotemporal stochastic resonance has now been achieved experimentally for the first time.

Rapid detection of respiratory pathogens circulating in indoor environments could facilitate improved infection prevention responses. In this proof-of-concept study, the authors develop a pathogen air quality monitor for real-time direct detection of SARS-CoV-2 aerosols and demonstrate its application in rooms of people with SARS-CoV-2 infections.

Routine coffee consumption is associated with a gut microbiome signature characterized by elevated levels of Lawsonibacter asaccharolyticus. The growth of this bacterium is stimulated by coffee in vitro and its activities may influence the biotransformation of coffee-associated metabolites.

The myeloma cell surface proteome regulates plasma cell biology and delineates therapy targets. Here, the authors profile the myeloma surfaceome at baseline and in drug resistance, finding the potential target CCR10, and include a streamlined approach to primary sample analysis.

Fungal spores can promote immune responses of both type 2 (IL-4 / IL-5 / IL-13) and type 17 (IL-17). Here the authors characterise the subsets of cDC2 associated with type 2 and type 17 allergic responses to fungal allergens and show that Mgl2⁺ cDC2 depletion reduces type 2 but not type 17 fungal airway inflammation.

Brown adipose tissue (BAT) produces heat by burning lipid triglycerides. Here, Berbée et al. show that pharmacological BAT activation protects hyperlipidemic mice from atherosclerosis, provided mice retain the metabolic capacity to clear cholesterol-enriched lipoprotein remnants by the liver.

The SARS-CoV-2 Assessment of Viral Evolution (SAVE) programme provides a real-time risk assessment of SARS-CoV-2 variants with the potential to affect transmission, virulence and resistance to infection- and vaccine-induced immunity.

Factors that determine the cellular tropism of SARS-CoV-2 beyond the host cell receptor, ACE2, are poorly defined. Here, the authors show that tonic activation of the cGAS-STING sensing pathway potently blocks SARS-CoV-2 replication in a subset of ACE2-expressing airway-derived cells.

The human germinal centre response to influenza virus vaccination is fuelled by the continued recruitment of naive B cells as well as pre-existing memory B cells.

Boussiotis and colleagues show that the tyrosine phosphatase SHP-2 regulates the differentiation and antitumor function of monocytes downstream of the inhibitory PD-1 receptor.

Multiomics and spatial mapping of tumor samples derived from a real-world cohort of patients with advanced renal cell carcinoma, as well as integration of transcriptomics and human leukocyte antigen genotyping data, provides a machine learning-derived signature of response to immune checkpoint blockade.

Cancer-associated fibroblasts (CAFs) are a predominant stromal cell population in the tumour microenvironment. Here, the authors demonstrate that αSMA + CAFs can form an immunological synapse with regulatory T cells (Tregs) in tumours, which results in Treg activation and expansion in a process that is antigen- and autophagy-dependent.

Intratracheal boosting with a bivalent Ad26-based SARS-CoV-2 vaccine results in substantial induction of mucosal humoral and cellular immunity and near-complete protection against SARS-CoV-2 BQ.1.1 in rhesus macaques.

Lymphatic malformation (LM) is a debilitating often incurable vascular disease. Using a mouse model of LM driven by a disease-causative PIK3CA mutation, the authors show that vascular growth is dependent on the upstream lymphangiogenic VEGF-C signalling, permitting effective therapeutic intervention.

IL-33, an IL-1 family member, plays dual roles as an intracellular transcription factor and as an extracellular alarmin of tissue damage. Verginis and colleagues identify a cell-intrinsic role for nuclear IL-33 stabilizing T_reg cell suppressor function in tumor environments.