2026-04-20 | Cytosol-Targeting Delivery of Non-Nucleotide STING Agonist Achieves Inhalable Nanoparticle-Based Anthrax Vaccine.

Inhalational anthrax is a deadly disease caused by inhalation of Bacillus anthracis spores. Current anthrax vaccines for human use have limitations including undefined components, limited mucosal immunity, and suboptimal adjuvant delivery. This study introduces 2 polymers, MP1 and MP2, each containing disulfide bonds. MP1 incorporates tertiary amines to induce proton sponge effect, while MP2 features terminal phenylboronic acid moieties for protein conjugation. Nanoparticle vaccine YM1.7 is created through self-assembly of MP1, MP2, and STING agonist MSA-2, followed by N─B coordination of recombinant protein antigen (rPA) on its surface. When administered via aerosolized intratracheal inoculation into the lung, YM1.7 is internalized by antigen-presenting cell and trafficked to the lysosome, where acidic environment dissociates N─B bond, releasing rPA for antigen presentation. Proton sponge effect allows nanoparticle to escape into the cytosol, and then disulfide bond cleavage triggered by cytosolic glutathione causes dissociation of nanoparticle and release of MSA-2 within the cytosol, significantly enhancing bioavailability of MSA-2 as an adjuvant. This spatiotemporal delivery mechanism elicits a coordinated innate, humoral, mucosal, and cell-mediated immune response in mice, providing strong protection against inhalational anthrax. Given its modular design nature, YM1.7 represents a promising platform for developing next-generation mucosal vaccines against infections and cancers.

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2026-02-21 | Clinical Characteristics and Survival of Hospitalized Anthrax Patients with Pleural, Pericardial, or Peritoneal Fluid Collections.

The prevalence of pleural, pericardial, or peritoneal effusions among anthrax patients is unknown, as is the impact of drainage on mortality. We identified hospitalized anthrax patients with effusions published 1920-2018 worldwide (N = 1108), excluding cases with insufficient clinical data. Two manuscript authors independently abstracted fluid collection and morbidity data. We evaluated how effusion drainage impacted mortality using logistic regressions. Effusions were present in 99 (13%) of 744 eligible anthrax patients; 65 (66%) of these died. Pleural effusions developed in 72% of patients with inhalation anthrax (N = 61), most often bilaterally. Similarly, 55% of ingestion anthrax patients (N = 55) developed peritoneal effusions. Pericardial effusions were rare (1.7%). Most pleural Gram stains or cultures obtained pre-antimicrobials were positive (83%). Of the 44 patients with clinically significant pleural effusions, only 59% received drainage. Drainage of these effusions was associated with survival (odds ratio [OR] 38.3, 95% confidence interval [CI]: 4.3-339.0), even when controlling for antimicrobials and/or antiserum. Most patients with fatal outcomes following drainage had either bilateral effusions with single-sided drainage or effusion recurrence. Although drainage of clinically significant peritoneal effusions was not associated with survival, laparotomy ± resection for peritonitis was associated (OR 53.6, 95% CI: 9.4-inf). Pleural drainage appears associated with survival. Most inhalation anthrax patients develop bilateral collections, and may require chest-tube insertions. Surgical source control is associated with survival for anthrax-associated peritonitis. Following a wide-area release of Bacillus anthracis, public health authorities should anticipate many patients may require source control (eg, chest tube drainage or surgery) and plan accordingly.

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