Reviews & Analysis

In this proof-of-concept study, we present a next-generation poxvirus vaccine that features a ‘two-in-one’ immunogen. Our protein vaccine construct, DAM, combines the monkeypox virus antigens A35 and M1, and was produced on the basis of structure-guided design. The DAM subunit vaccine elicited superior antiviral immunity with safety compared to cocktail vaccines or a live vaccinia virus vaccine.

In this Review, Wilfahrt and Delgoffe discuss how T cells integrate nutrient sensing with activating stimuli to shape their differentiation and sensitivity to metabolites.

Sepsis is a global health issue in great need of effective therapies. Analysis of gene expression profiles in different tissues and at the whole-body level in mice enabled the characterization of the organism-wide host response to sepsis, which will help to build a unified mechanistic framework for the disease.

Anatomical separation exists between the generation and lodging sites of plasma cells. Transcriptome analysis of tissue-resident plasma cells provides important insights into how newly generated plasma cells acquire longevity.

The effectiveness of pneumococcal vaccines declines with age for unknown reasons. We studied the responses of older adults to the 23-valent PPSV23 and the 13-valent PCV13, identifying distinct baseline immune characteristics associated with vaccine responsiveness, including a cytotoxicity signature associated with weaker responses to PCV13.

The alarmin IL-33 activates type 1 and type 2 immune cells via its receptor ST2 in a context-specific manner. We discovered a type 1 immunity-restricted promoter of the ST2-coding gene Il1rl1, which is located far upstream of the curated gene and is crucial for antiviral CD8⁺ cytotoxic T cell and CD4⁺ T_H1 cell responses.

The use of T cell receptor signatures to track activated spike-specific T cell dynamics between recovery from SARS-CoV-2 infection and subsequent mRNA vaccination shows that vaccination effectively recruits pre-existing memory and new CD8⁺ T cell clonotypes.

Epithelial cells, macrophages and T cells are linked in a previously unknown regulatory circuit. Sensing of interferon-γ triggers antigen presentation by colonic epithelial cells, enabling T cells to lower extracellular ATP levels and reduce inflammation.

Expressing chimeric antigen receptors (CARs) in macrophages has led to promising results in preclinical and clinical work. Now, induced pluripotent stem cells have been combined with a second-generation CAR to achieve macrophage rewiring and to broaden the applicability of the approach to solid malignancies.

T cells exist in many functional states, and dynamic transitions from one state to another affect the outcome of adoptive T cell therapy. FOXP1 and KLF2 are now identified as transcriptional regulators of the stemness of CD8⁺ CAR-T cells and the bifurcation of stem-like CD8⁺ CAR-T cells into effector and exhausted subsets, respectively.

We describe a system for introducing guide RNAs (gRNAs) to Cas9-expressing hematopoietic stem cells, which are used to generate mice with gene knockouts in the immune system. By using different gRNA-containing vectors and Cas9-expressing mice, we created systems for knockout of single genes or pairs of genes constitutively or inducibly.

BCG vaccination provides protection against unrelated viral infections. The vaccine induces protective integrated organ immunity through biphasic activation of innate and adaptive immune cells.

Mouse macrophages express specialized genes particular to the organs they inhabit, but whether the same applies in humans is unclear. In human peritoneal fluid, we identified many macrophage phenotypes, including two specialized macrophage types that corresponded to distinct mouse peritoneal macrophages. However, their abundances were markedly different between species.

In this Review, Netea and colleagues summarize the latest research that contributes to our understanding of the pathophysiology of sepsis, and how this contributes to a new treatment approach through personalized immunotherapy.

In this Review, the authors describe the mechanisms that account for the generation and immune recognition of neoantigens that are not derived from DNA mutations, with a special focus on relevance to cancer and autoimmunity.