anti-H5N1 avian influenza antibodies (Fabenflu / FBF001)

Single-component self-assembling protein nanoparticles displaying stabilized prefusion-closed hemagglutinin trimers for influenza vaccine development.

Zhang Yi-Nan YN, Zhu Xueyong X, Braz Gomes Keegan K, Lee Yi-Zong YZ et al.

Current influenza vaccines primarily target hemagglutinin (HA), the major viral surface glycoprotein and principal determinant of neutralizing antibody (NAb) responses. However, antigenic drift and shift, together with HA's intrinsic metastability and low-pH sensitivity, limit broad and durable vaccine protection. Here, we stabilize HA in its prefusion-closed conformation through structure-guided amino acid substitutions. Targeting a conserved residue in the HA2 central triple helix-N95 in influenza A and Q95 in influenza B-provides a core design principle for modulating HA metastability across influenza A subtypes and both influenza B lineages, although the effects vary across viral groups. Using H1 CA09 and H3 HK68 as representative strains, we display stabilized HA trimers on 24-mer ferritin and 60-mer multilayered single-component self-assembling protein nanoparticles (SApNPs). In mice, HA-presenting SApNPs exhibit prolonged retention in lymph node follicles and elicit more robust germinal center responses compared with soluble trimers. Stabilized HA trimers and SApNPs induce functional antibody responses and confer varying levels of protection against homologous, heterologous, and cross-lineage viral challenges. Glycan modification enhances NAb induction or protection in some settings. Together, these findings provide mechanistic insights into HA metastability and establish a rational design framework for next-generation HA-based influenza vaccines.

Predictive value of the prognostic nutritional index and aggregate index of systemic inflammation for pulmonary complications in children with influenza.

Wu Yuanyuan Y, Zhang Jianjian J, Ke Xuejia X, Pan Junping J et al.

Pulmonary complications drive morbidity in pediatric influenza, but early risk stratification remains challenging. This study evaluated the predictive utility of the prognostic nutritional index (PNI) and the aggregate index of systemic inflammation (AISI)-accessible biomarkers of immune-nutritional and inflammatory status-for pulmonary complications in pediatric influenza. This retrospective study analyzed 248 pediatric patients with influenza admitted between January 2022 and December 2024. PNI and AISI were calculated from admission laboratory data. Multivariable logistic regression and receiver operating characteristic (ROC) curves were utilized to evaluate the independent and combined predictive performance of PNI and AISI for the development of pulmonary complications. Pulmonary complications developed in 86 patients (34.7%). These patients exhibited significantly lower PNI and higher AISI than those without complications (both P<0.001). Furthermore, PNI correlated inversely, and AISI positively, with disease severity markers including C-reactive protein (CRP), procalcitonin, fever duration, and hospital length of stay (all P<0.001). Multivariable analysis identified prolonged fever, decreased PNI, and elevated AISI as independent predictors of pulmonary complications. The combined PNI-AISI model showed higher apparent discriminatory performance than PNI or AISI alone [the area under the receiver operating characteristic curve (AUC): 0.913, sensitivity: 87.2%, specificity: 85.2%]; however, further validation is required to confirm its generalizability. Decreased PNI and elevated AISI independently predict pulmonary complications and disease severity in pediatric influenza. Integrating these indices provides a highly accurate, accessible, and physiologically grounded tool for early risk stratification, optimizing clinical decision-making.

Influenza vaccination in children with underlying conditions: affirming effectiveness and confronting gaps.

Geissler Kimberley H KH, Peacock-Chambers Elizabeth E

Combination Of Bispecific Antibodies Enable Targeted TNFRSF Agonism and Effective Antitumor Activity.

Diby Lucie L, Malinge Pauline P, Moine Valery V, Nouveau Lise L et al.

4-1BB is an inducible costimulatory molecule that requires receptor clustering to boost anti-cancer immune response. However, the clinical development of monoclonal antibodies targeting 4-1BB has been constrained by toxicities driven by systemic activation. To address this, bispecific antibodies (bsAbs) have been developed to selectively activate 4-1BB in a HER2-dependent manner. 4-1BB activation was assessed using 4-1BB-GFP and reporter cells, before evaluating the cytokine production and tumoricidal activity of primary T cells. In vivo antitumor efficacy was assessed in PBMC-xenograft and syngeneic h4-1BB/h4-1BBL transgenic (Tg) models, the latter enabling comparison of systemic inflammatory responses with urelumab. Combining two 4-1BB x HER2 bsAbs that share a 4-1BB epitope but bind non-overlapping HER2 epitopes markedly enhanced 4-1BB clustering and signaling, and correlated with HER2 expression levels, with strong T-cell activation and tumor growth inhibition. In the PBMC-xenograft model, combining the bsAb pair with a T-cell engager potentiated antitumor activity and increased T-cell infiltration within the tumor microenvironment. In the syngeneic Tg model, the paired bsAbs maintained robust efficacy while mitigating peripheral inflammation compared to urelumab. Overall, we established a bsAb combination strategy that amplifies HER2-driven 4-1BB+ T-cell activation and provides an applicable framework for targeting other tumor necrosis factor receptor superfamily members.