Biology subjects

Le Sage, V. M.

Publications and source records attributed to Le Sage, V. M..

4 recordsLinked to original sources

bioRxiv2026

A lethal human H5N5 influenza virus isolate exhibits low pandemic risk traits

In fall of 2025, a fatal infection of highly pathogenic avian influenza (HPAI) virus H5N5 occurred. To define the risk of this emerging virus to humans, we performed a comprehensive analysis based on our established triage. Serological analysis revealed that humans across all birth years had no detectable neutralizing antibodies to this H5N5 isolate. Further characterization revealed a lack of phenotypic signatures associated with epidemiologically successful influenza viruses in humans, including reduced replication in human airway cells and an avian-like pH of inactivation. Additionally, assessment of H5N5 in ferrets revealed a lack of direct contact transmission and moderate disease severity. H5N5 infection in ferrets with prior immunity against the 2009 H1N1 pandemic strain resulted in fewer clinical signs and reduced viral shedding. Together our data suggest that the current H5N5 HPAI lineage poses a low pandemic risk. ImportanceHPAI H5N5 viruses have caused widespread infection and death in avian species, and characterizing their pandemic risk traits is critical to understanding the threat posed to humans. In this work we analyzed an isolate that resulted in a human fatality in 2025. We found that this strain lacks many key features of influenza viruses with epidemiological success in humans including reduced growth in human lung cultures, a pH of inactivation less than 5.0, and lack of transmission to cohoused recipient ferrets. Prior immunity with seasonal H1N1 strain also reduced the viral load and disease burden of the virus. Taken together, these data suggest that currently circulating H5N5 poses a low risk to humans but highlights the importance of phenotypic characterizations for future risk assessments as the virus evolves in wild birds.

microbiology↗

bioRxiv2026

Optimizing an avian influenza vaccine using a novel Bacterial Enzymatic Combinatorial Chemistry (BECC) TLR4 adjuvant

The development of broadly protective and dose-sparing influenza vaccines remains a critical challenge, particularly for zoonotic H5N1 strains with pandemic potential. This study evaluates BECC470s, a synthetic TLR4 adjuvant, for its ability to enhance the immunogenicity and protective efficacy of recombinant H5 hemagglutinin (rHA) vaccination in murine models. BECC470s-adjuvanted rHA elicited robust IgG1/IgG2a antibody responses and complete survival following homologous 2004 H5N1 challenge in a prime-boost model. Although BECC470s broadened antibody binding to both variable HA head and conserved stalk domains by ELISA, functional neutralizing antibody responses were restricted to the matched 2004 H5N1 isolate, with no detectable neutralization of H5N1 viruses isolated in 2022 or 2024. These data indicate that BECC470s enhances the magnitude and apparent breadth of binding antibody responses while maintaining strain-specific neutralizing activity, supporting its potential as an adjuvant for next-generation influenza vaccines while underscoring the need for further optimization to achieve true cross-neutralizing protection.

immunology↗

bioRxiv2025

A replicating recombinant vesicular stomatitis virus model for dairy cattle H5N1 influenza virus glycoprotein evolution

A panzootic of highly pathogenic avian influenza (HPAI) H5N1 viruses from clade 2.3.4.4b has triggered a multistate outbreak in United States dairy cattle and an unknown number of human infections. HPAI viruses are handled in specialized biocontainment facilities. Ethical considerations limit certain experimental evolution experiments aimed at assessing viral resistance to potential therapeutics. We have developed a replicating recombinant vesicular stomatitis virus (rVSV) where we replaced its glycoprotein with the hemagglutinin (HA) and neuraminidase (NA) genes of a 2.3.4.4b H5N1 virus (rVSV-H5N1dc2024), which is free of these constraints. This virus grows to high titers and encodes a fluorescent reporter to track infection. We demonstrate the utility of rVSV-H5N1dc2024 in neutralization experiments, evaluating antibody escape and characterization of resistance mutations to NA inhibitors. rVSV-H5N1dc2024 or similar viruses may accelerate efforts to develop and evaluate interventions against this emerging threat to human and animal health. IMPORTANCEHighly pathogenic avian influenza H5 viruses have spread globally, established sustained transmission in mammals and caused human infections. Research on these viruses is restricted to high biocontainment laboratories. We report the characterization and utility of a surrogate, replicating virus that displays the two key influenza glycoproteins, hemagglutinin and neuraminidase, that can be safely handled in most research laboratories. This virus is amenable for the evaluation of antiviral antibodies and small molecule inhibitors and the evolution of viral resistance to these agents. This virus can enable a wider range of researchers to study H5 viruses of pandemic concern.

microbiology↗

bioRxiv2023

Seasonal influenza viruses decay more rapidly at intermediate humidity in droplets containing saliva compared to respiratory mucus

Expulsions of virus-laden aerosols or droplets are an important source of onward respiratory virus transmission and can originate from both the oral and nasal cavity of an infected host. However, the presence of infectious influenza virus in the oral cavity during infection has not been widely considered, and thus little work has explored the environmental persistence of influenza virus in oral cavity expulsions that may facilitate transmission. Using the ferret model, we detected infectious virus in the nasal and oral cavities, suggesting that virus can be expelled into the environment from either anatomical site. We also assessed the stability of two influenza A viruses (H1N1 and H3N2) in droplets of human saliva or respiratory mucus over a range of relative humidities. We observed that influenza virus infectivity decays rapidly in saliva droplets at intermediate relative humidity, while viruses in airway surface liquid droplets retain infectivity. Virus inactivation was not associated with bulk protein content, salt content, or droplet drying time. Instead, we found that saliva droplets exhibited distinct inactivation kinetics during the wet and dry phases at intermediate relative humidity and that droplet residue morphology may lead to the elevated first-order inactivation rate observed during the dry phase. Additionally, distinct differences in crystalline structure and nanobead localization were observed between saliva and airway surface liquid droplets. Together, our work demonstrates that different respiratory fluids exhibit unique virus persistence profiles and suggests that influenza viruses expelled from the oral cavity may contribute to virus transmission in low and high humidity environments. ImportanceDetermining how viruses persist in the environment is important for mitigating transmission risk. Expelled infectious droplets and aerosols are composed of respiratory fluids, including saliva and complex mucus mixtures, but how influenza viruses survive in such fluids is largely unknown. Here, we find that infectious influenza virus is present in the oral cavity of infected ferrets, suggesting that saliva-containing expulsions can play a role in onward transmission. Additionally, influenza virus in droplets composed of saliva degrades more rapidly than virus within respiratory mucus. Droplet composition impacts the crystalline structure and virus localization in dried droplets. These results suggest that viruses from distinct sites in the respiratory tract could have variable persistence in the environment, which will impact viral transmission fitness.

microbiology↗