anti-H5N1 avian influenza antibodies (Fabenflu / FBF001)

Neuropathology, novel tissue tropism, and evidence of vertical transmission in South American pinnipeds naturally infected with high pathogenicity avian influenza H5N1 virus in Argentina.

Fiorito Carla C, Fernández Antonio A, Colom-Rivero Ana A, Alonso-Almorox Paula P et al.

In 2023, high pathogenicity avian influenza (HPAI) H5N1 outbreaks caused mass mortality events affecting pinnipeds throughout South America. Here, we present the clinical, pathological, immunohistochemical, and molecular findings associated with HPAI H5N1 infection in 3 South American sea lions (Otaria flavescens) and 1 southern elephant seal (Mirounga leonina) stranded during the outbreak in Chubut, Argentina. Neurological signs were observed in 2 sea lions, with 1 also exhibiting respiratory distress. Necropsies were conducted on all 4 animals. Neuropathology revealed mild-to-severe lymphohistiocytic (2/4) to mixed neutrophilic (2/4) meningoencephalitis with neuronal necrosis, neuronophagia, glial cell proliferation, multifocal hemorrhage, and perivascular cuffing in all animals. Novel findings for HPAI H5N1-infected pinnipeds included choroid plexitis (2/4) and myelitis (2/4). Immunohistochemistry for viral nucleoprotein was positive in 3 of 4 animals and involved neurons (3/3), glial cells (3/3), and ependymal cells (2/3). Viral-related systemic findings included multifocal necrotizing myocarditis in the elephant seal and multifocal necrotizing placentitis in a sea lion, with HPAI virus detected within fetal tissues. Pulmonary lesions were minimal and were limited to multifocal necrosis of bronchial glands in 1 sea lion. HPAI H5 clade 2.3.4.4b virus was confirmed by polymerase chain reaction and sequencing in all animals. These findings indicate a predominance of central nervous system involvement in HPAI H5N1-infected pinnipeds and expand the recognized spectrum of virus-associated lesions, identifying novel tissue tropisms and transmission routes.

Subclass switching enhances protective efficacy of a non-neutralizing H7N9 avian influenza antibody.

Dou Yunlong Y, Zhao Jiangyan J, He Xiaozheng X, Song Seung-Un SU et al.

Non-neutralizing antibodies contribute to protection against the H7N9 subtype avian influenza virus through Fc effector functions. Antibody subclass plays a critical role in determining binding affinity to Fc receptors (FcR) and downstream Fc effector functions. In this study, to assess whether antibody subclass switching can enhance antibody protective efficacy, subclass of a non-neutralizing monoclonal antibody (mAb) against the hemagglutinin of H7N9 virus was switched from IgG1 to IgG2a, and their activity and protective efficacy were assessed. Subclass switching caused no significant changes in antigen binding, hemagglutination-inhibition and virus neutralizing activities of the antibody. The hybridoma-derived mAb conferred no protection against H7N9 virus infection. Interestingly, both IgG2a and IgG1 antibodies produced in CHO cells provided full protection against mortality caused by a sublethal H7N9 virus challenge. Upon lethal challenge, IgG2a antibody conferred 70% protection, whereas its IgG1 counterpart only provided 30% protection. However, both antibodies did not decrease virus loads in mouse lungs. Moreover, compared to the IgG1 antibody, affinity of the subclass-switched IgG2a antibody to FcR was significantly increased, as evidenced by enhanced binding of the antibody to recombinant murine FcγRI and to FcRs on murine macrophages. Our findings highlighted a benefit of subclass-engineering to antibody modification and development of therapeutic antibodies.

Author Correction: GGCX promotes Eurasian avian-like H1N1 swine influenza virus adaption to interspecies receptor binding.

Zou Jiahui J, Jiang Meijun M, Xiao Rong R, Sun Huimin H et al.

Evaluating transient risk factors for avian influenza outbreaks in Canada using case-crossover study and machine learning.

Sekhavati Iman I, Dara Rozita R, Sharif Shayan S, Aliabadi Amir A AA

Highly Pathogenic Avian Influenza (HPAI) poses a severe biological and economic threat to the Canadian poultry industry. The transient and day-to-day meteorological and regional triggers remain poorly quantified due to spatial confounding in traditional epidemiological models. To isolate these triggers, this study utilizes a time-stratified case-crossover design, integrating a veterinary surveillance dataset of infected premises (2022-2024) with ERA5 meteorological reanalysis data. We employ the conditional difference method optimized with Ridge (L2) regularization. The national model demonstrated discriminative ability (ROC-AUC = 0.978; Brier score = 0.060). The analysis identified local proximity to an active outbreak as the strongest statistical predictor, with patterns consistent with wind-mediated transmission amplified by high wind speeds and relative humidity. A provincial-level stratification revealed that transmission mechanics are geographically distinct. In dense agricultural zones, extreme farm proximity dictates an effect that overpowers ambient weather factors. In dispersed geography of the Prairies, meteorological factors dominate infection triggers. These findings suggest that mitigation interventions must be tailored to regional factors.