Volume 23 Issue 12, December 2022

Understanding immune determinants of vaccine-mediated immunogenicity could further provide rational vaccine design. Two research groups revealed pre-existing and early innate immune signatures associated with better vaccine-mediated antibody responses.

Mechanisms that explain the hygiene hypothesis for allergy and asthma are unclear. A mouse model that cohouses ‘dirty’ pet-store mice with clean laboratory mice might help to understand this immunology.

Zhang et al. describe how meningeal MAIT cells maintain meningeal barrier integrity via the secretion of antioxidants, which also limit neuroinflammation and preserve spatial learning.

The bacillus Calmette–Guérin (BCG) vaccine induces homotypic protection against tuberculosis and, surprisingly, heterotypic protection against other pathogens. New work shows that BCG vaccination causes leakage of microbial gut metabolites into circulation, which induces changes in alveolar macrophages protective against pneumonia.

The US National Institute of Allergy and Infectious Diseases (NIAID) convened a virtual workshop in July 2022 to address the research landscape and identify gaps and opportunities in the understanding of durable vaccine protection.

Cohousing pet-store mice with laboratory mice leads to the natural transfer of microbes and subsequent inflammation in laboratory mice. Lung group 2 innate lymphoid cells — rapid responders to airway allergens — are transiently inhibited by inflammatory signals, but their activity recovers once the active infection subsides.

We isolated CD4⁺ T cell clones from healthcare workers infected with SARS-CoV-2 during the first COVID-19 wave and identified 21 epitopes across three viral proteins: spike, membrane and nucleoprotein. Focusing on spike protein, for seven of ten epitopes mutated in variants of concern, we found that T cell recognition was impaired.

The fungal pathogen receptor dectin-1 instructs the development of non-pathogenic T_H17 cells via TGFβ activation. This process requires strict control of the expression of type I interferon to ensure a delicate balance in the expression of its effector genes that control the release of active TGFβ.

Halper-Stromberg and Jabri discuss the molecular and functional adaptations to inflammatory or pathogenic stimuli that shape the immune identity of each individual.

Parenteral BCG vaccination has been shown to drive innate immune memory responses that can affect the response to pathogens other than mycobacteria. Here the authors show an innate immune memory mechanism whereby subcutaneous BCG vaccination alters the intestinal microbiome and in turn can train alveolar macrophages in the lungs.

Here the authors show that mice exposed to a variety of pathogens initially have impaired innate type 2 responses to lung allergens, but reactivity resets over time, indicating that microbial experience does not stably inhibit innate immunity to allergens.

Yang and colleagues report that MAIT cells are present in the meninges where they play an essential role in repressing tissue ROS accumulation and preserving meningeal barrier integrity.

Based on the identification of CD4⁺ T cell clones specific for distinct epitopes in the SARS-CoV-2 proteins, Long and colleagues characterize how mutations in these epitopes lead to loss of recognition by the CD4⁺ T cells elicited by natural infection or vaccination.

Gringhuis and colleagues show that the extent of type I IFN responses induced by fungal stimulation in human DCs modulate the activation of TGF-β and the production of pathogenic or non-pathogenic T_H17 cells.

Haimon et al. examine the function of microglia in a relapsing–remitting mouse model of multiple sclerosis, finding that these cells preferentially interact with regulatory T cells compared with effector T cells, and that these cognate interactions require interferon-γ signaling and are critical to maintain regulatory T cell activity.

Farrar and colleagues perform an extensive analysis of Ncor1/2 function in B cell development. Loss of both genes results in defective pre-BCR signaling, increased accessibility of STAT5 chromatin motifs and inappropriate Rag gene expression, leading to accelerated leukemic transformation.

Sekaly and colleagues reveal a common pre-vaccination peripheral blood transcriptional signature that is predictive of antibody responses across 13 different vaccines.

Pulendran and colleagues perform a comparative analysis of transcriptional responses of healthy young adults across 13 different vaccines. They find that while a common transcriptional program is shared across many vaccines, there is significant heterogeneity especially in the kinetics of immune responses.