Cross-clade #protection against #human #H5N1 isolates by a clade 2.3.4.4b HA #mRNA #vaccine in mice

 

Abstract

The recent spread of clade 2.3.4.4b H5N1 high pathogenicity avian influenza (HPAI) viruses into mammals, despite limited human infections to date, has raised serious public health concerns and highlights the need for rapidly deployable vaccines, such as mRNA-based platforms, to strengthen pandemic preparedness. Here, we evaluated the effectiveness of an mRNA vaccine encoding the HA of NIID-002, a WHO-recommended H5 candidate vaccine virus (CVV) derived from A/Ezo red fox/Hokkaido/1/2022 (clade 2.3.4.4b) against A/Texas/37/2024 (TX37; clade 2.3.4.4b) and A/Cambodia/2311257/2023 (Cam23; clade 2.3.2.1e). The mRNA was formulated with ssPalmO, a low-inflammatory self-degradable ionizable lipid nanoparticle (LNP). BALB/c mice were immunized intramuscularly twice with the mRNA-LNP vaccine containing either 1 μg or 10 μg of H5 HA mRNA. After boosting, strong, dose-dependent serum IgG responses against NIID-002 HA were detected by ELISA. The mice were then challenged with a lethal dose of homologous TX37 or heterologous Cam23. All mice in the 10-μg group survived both challenges, demonstrating robust cross-clade protection. In the 1-μg group, complete protection without significant body weight loss was observed against TX37, whereas partial protection was observed following Cam23 challenge. Viral titers were significantly reduced in multiple tissues of the vaccinated mice compared to the unvaccinated controls. Our findings demonstrate that the NIID-002-HA mRNA vaccine confers protection against homologous and heterologous zoonotic H5N1 strains in a mouse model. This low-inflammatory ssPalmO-LNP platform thus supports safe, rapid vaccine development against emerging H5N1 viruses with pandemic potential.

Source: 

Link: https://doi.org/10.1016/j.vaccine.2026.129215

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Increased circulation of #influenza #H1N1pdm09 viruses with reduced susceptibility to #oseltamivir, #Germany 2024–2026

 

Highlights

    • The National Influenza Center for Germany (Germany NIC) detected an increase in the prevalence of A(H1N1)pdm09 viruses carrying the neuraminidase substitution NA-S247N, rising from 1.16% circulating in the 2024/25 influenza season to 56.8% in the 2025/26 season.

    • The NA-S247N substitution reduced oseltamivir susceptibility slightly; combined NA-S247N/NA-I223V/T substitutions showed reduced inhibition according WHO criteria.

    • Continuous molecular and phenotypic surveillance is essential for public health and the early detection of viruses with reduced susceptibility to antiviral drugs.

    • Rapid pyrosequencing supports the routine surveillance of neuraminidase substitutions associated with reduced susceptibility to antivirals.

    • The findings illustrate the Germany NIC's 30-year contribution to antiviral susceptibility monitoring.

Abstract

Background

Oseltamivir is still considered to be the first-line antiviral treatment for severe seasonal influenza. However, resistance to neuraminidase (NA) inhibitors poses significant challenges to influenza management. Since the 2023/24 season, A(H1N1)pdm09 viruses carrying neuraminidase substitutions (NA-I223V and/or NA-S247N) have emerged in Germany, other EU/EEA countries, and some of the World Health Organization (WHO) regions. These viruses have been linked to reduced oseltamivir susceptibility.

Methods

A rapid RT-PCR/pyrosequencing assay was developed and validated to detect NA-I223X and NA-S247X substitutions. Subsequently, a total of 765 A(H1N1)pdm09 viruses detected in Germany during the 2024/25 and 2025/26 influenza seasons were characterized phenotypically using fluorometric NA inhibition testing and/or genotypically using next-generation sequencing and pyrosequencing.

Results

The prevalence of A(H1N1)pdm09 viruses bearing the NA-S247N substitution increased from 1.2% in the 2024/25 season to 56.8% in the 2025/26 season, accounting for up to 80% of analyzed viruses by March 2026. Viruses carrying NA-S247N exhibited higher oseltamivir IC50 values than wild-type viruses. Combinations of NA-S247N with substitutions at position 223 demonstrated an additional increase. In viruses carrying the combined NA-S247N and NA-I223V/T substitutions oseltamivir showed reduced inhibition with increased IC50 values of up to 17-fold compared to wild type viruses.

Conclusions

The accumulation of NA substitutions in A(H1N1)pdm09 influenza viruses, particularly NA-S247N in combination with NA-I223V/T, substantially reduces susceptibility to oseltamivir. The marked increase in NA-S247N prevalence suggests that this substitution is becoming persistent rather than transient. Targeted pyrosequencing is a practical tool for the early detection of emerging resistance-associated substitutions.

Source: 

Link: https://doi.org/10.1016/j.ijmm.2026.151745

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Multi-Country #Human-to-Human #Andes Virus #Outbreak on a Cruise #Ship: A Disaster #Report on Prehospital, Health Care Facility, and Public Health System Challenges – Essential Knowledge for Frontline Clinicians

 

Abstract

The Andes Virus (ANDV) outbreak reported on May 2, 2026, aboard a luxury vessel departing from Ushuaia, Patagonia, Argentina, was caused by an Orthohantavirus unique in its person-to-person transmissibility in contrast to zoonotic transmission characteristic of better-known hantaviruses. Containment required coordinated international management because passengers and crew embarked and disembarked at several international ports-of-call prior to outbreak recognition, resulting in cross-border transmission potential. Among those who disembarked, several traveled on flights to various destinations. Cases subsequently manifested in multiple countries, including Tristan da Cunha, Spain, France, Switzerland, South Africa, Canada, and The Netherlands. Upon notification, international health authorities implemented containment measures, such as contact tracing, quarantine, and isolation. Uniquely, ANDV poses distinctive risks due to its immediately prodromal presymptomatic transmission potential, initial non-specific flu-like symptoms, prolonged incubation period, conceivable long-term neurologic and endocrinologic sequalae, high case fatality rates (CFRs), and possibility of international dissemination. This report describes the successful management of a multi-national outbreak associated with cruise-ship travel, a setting with unique challenges. It also examines implications and challenges for prehospital, health care facility, and public health systems for future ANDV outbreaks. The event was characterized by delayed recognition, international spread, and complex coordination across multiple jurisdictions and sectors, including medical and public health authorities, policy- and decision-makers, crisis and emergency risk-communication experts, media, logistics, transportation, and security. Rapid implementation of public health measures coupled with clinician implementation of the Identify-Isolate-Inform (3I) model, a clinical framework to detect and prevent the spread of infectious disease, at the prehospital and health care facility levels are critical actions that can contain future ANDV outbreaks.

Source: 

Link: https://doi.org/10.1017/S1049023X26109108

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Notes from the Field: #Fatal Pneumonic #Plague — Coconino County, #Arizona, July 2025

 

Summary

    ° What is already known about this topic?

        § Pneumonic plague is a rare and often fatal disease that can be transmitted by respiratory droplets from animals or persons infected with Yersinia pestis bacteria.

    ° What is added by this report?

        § In July 2025, Arizona reported its first pneumonic plague death since 2007, in a man with occupational exposure to ill cats. Two days after the patient’s death, preliminary diagnostic test results supported a suspected pneumonic plague diagnosis, prompting immediate identification of potentially exposed persons for postexposure prophylaxis.

    ° What are the implications for public health practice?

        § In areas with endemic plague, preliminary diagnostic test results combined with clinical suspicion for pneumonic plague can result in timely public health interventions.

Abstract

Pneumonic plague is transmitted through inhalation of respiratory droplets containing the bacterium Yersinia pestis and has a nearly 100% case-fatality rate when untreated. Although Y. pestis is endemic among rodents in northern Arizona, only eight human plague cases were reported in Arizona during 2000–2024. In July 2025, Arizona reported its first pneumonic plague death since 2007.

Source: 

Link: http://dx.doi.org/10.15585/mmwr.mm7538a2

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Two incursions, two viruses: emergence of a second novel #Shamonda virus clade, #Germany, 2026

 

Abstract

Following the emergence of Shamonda virus (SHAV) in Europe in 2026, we identified a second, genetically distinct SHAV clade in cattle in Germany. Consistent differences across all three genome segments together with divergent regional distribution patterns indicate independent introductions. We have designated the two clades as SHAV Europe 1 (SHAV-EU1) and SHAV Europe 2 (SHAV-EU2). The unexpected co-circulation of these two clades has important implications for diagnostics, surveillance, host range assessment, risk evaluation and control measures.

Source: 

Link: https://doi.org/10.2807/1560-7917.ES.2026.31.39.2600756

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#MERS-CoV in #Africa: a One Health #review of the silent #reservoir

 

Summary

Africa harbours more than 80% of the world’s dromedary camels, with a pooled MERS-CoV seroprevalence of 73·7%; however, no autochthonous outbreak in humans has been documented. In this Review, we weigh five interacting explanations for the absence of documented human outbreaks based on the strength of the evidence for each explanation. The primary explanation is virological; many, although not all, African clade C MERS-CoV strains show reduced replication competence in human respiratory tissues, and clade C strains have not become established in Arabian camels or humans despite decades of large-scale export from the Horn of Africa into the world’s most intensively monitored MERS-CoV surveillance system. Environmental contexts, including dry-season herd aggregation, drought, and calving-linked shedding, influence when MERS-CoV exposure occurs in humans. Surveillance limitations, dispersed exposure among the African population particularly pastoralists, lower comorbidity burden than that in affected populations in the Arabian regions, and absent nosocomial amplification are secondary explanations, largely downstream of the primary factors. Although longitudinal cohort studies using enhanced diagnostics detected sporadic spillover in Africa, these infections were asymptomatic. The presence of clade B strains and interclade B×C recombinants in Egyptian camels are surveillance priorities and not evidence of MERS-CoV emergence in humans. Africa’s silent reservoir is therefore not a safe one: continued clade C circulation, alongside emerging clade B introductions and interclade recombinants, could shift this balance, underscoring the need for sustained genomic and human surveillance of the reservoir.

Source: 

Link: https://doi.org/10.1016/j.lanmic.2026.101530

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#Andes Virus — A Clinical #Review

 

Summary

Andes virus (ANDV) is the sole orthohantavirus with documented human-to-human transmission. We summarize the epidemiology and clinical features of ANDV infection and review best practices in clinical management, as based on published expert consensus guidelines, field experience, and clinical trials. We also evaluate currently available and investigational treatments (including the use of antiviral agents), assess emerging monoclonal antibody therapies, and outline prospects for vaccine development. Finally, we discuss important infection prevention and control measures.

Source: 

Link: https://www.nejm.org/doi/full/10.1056/NEJMra2606651

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#SARS-CoV-2-specific monoclonal #antibody AER002 in #LongCOVID: an exploratory randomized phase 2a mechanistic trial

 

Abstract

Persistence of SARS-CoV-2 has been proposed as a biological driver of Long COVID, a disabling chronic illness with no proven treatments. We conducted an exploratory, placebo-controlled, double-blind, 2:1 randomized mechanistic trial (NCT05877508) of the SARS-CoV-2-specific monoclonal antibody AER002 in 36 participants who met the World Health Organization case definition of Long COVID. After baseline characterization, participants received a single infusion and were followed for 360 days. The primary endpoint was the PROMIS-29 Physical Health Summary Score (PHSS) at 90 days; secondary and exploratory endpoints included patient-reported and objective measures of physical and neurocognitive function as well as blood-, imaging-, and tissue-based biomarkers. While AER002 was safe and well tolerated, no significant differences in physical health, quality of life, objective measures of physical function or cognition, or blood-based biomarkers were demonstrated between the treatment and control arms. In a post-hoc analysis, participants with a lower baseline SARS-CoV-2 antibody level and higher drug exposure were more likely to perceive treatment benefit based on the Patient Global Impression of Change scale (p < 0.05 for anti-S, S1, and RBD). Although AER002 was not efficacious in this proof-of-concept study, our findings could inform future trials using monoclonal antibodies to target viral persistence in Long COVID.

Source: 

Link: https://www.nature.com/articles/s41467-026-77925-y

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N70S/Y155H Combined #Mutation of #Neuraminidase of Avian #Influenza #H9N2 Virus confers #oseltamivir and #zanamivir #resistance and pathogenicity to Mice

 

Highlights

    • H9N2 viruses recently circulating in China harbors novel N70S/Y155H dual mutations in N2;

    • H9N2 viruses with N70S/Y155H mutations exhibit high pathogenicity to BALB/c mice.

    • N70S/Y155H linked mutations in N2 confer resistance to oseltamivir and zanamivir, rather than peramivir.

    • Neuraminidase inhibitors exhibited limited efficacy on H9N2 virus with novel N70S /Y155H dual mutations.

Abstract

Recently, H9N2 avian influenza virus (AIV) poses a significant threat to both the poultry industry and public health. Therefore, investigating the impact of its neuraminidase mutations on susceptibility to neuraminidase inhibitors (NAIs) is of great importance for clinically preventing potential cross-species transmission of H9N2. In this study, our results revealed that NAI resistance-related mutations of most H9N2 viruses isolated from China during 1998 to 2024 mainly occurred at positions N70S, E119A/D/G/V, Q133K, Q136A, D151E, Y155H, I222V, R224K, E276D, R292K, N294S, and R371K. Among them, the combined N70S and Y155H mutations are common characteristics of H9N2 viruses circulating in recent years. In vivo experiments demonstrated that these H9N2 viruses harboring the combined N70S and Y155H mutations exhibit high pathogenicity to BALB/c mice without prior adaption. In vitro neuraminidase inhibition assays confirmed that these H9N2 viruses bearing the N70S/Y155H mutations exhibited greater reduced inhibition than their counterparts bearing the N70S or Y155H single mutation to oseltamivir and zanamivir, but remained highly sensitive to peramivir. Notably, the in vivo protective effect of NAIs against H9N2 virus with combined N70S and Y155H mutations is limited, possibly due to the restricted ability of these drugs to ameliorate the excessive inflammatory responses. Therefore, there is an urgency to strengthen research on epidemiological surveillance and prevention strategies for avian influenza H9N2 harboring these mutations.

Source: 

Link: https://doi.org/10.1016/j.antiviral.2026.106540

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#Maternal #vaccination against #COVID19, #influenza, #pertussis, and #RSV: a scoping review

 

Abstract

Pregnancy and early infancy are periods of heightened vulnerability, with SARS-CoV-2 and influenza infections potentially linked to adverse pregnancy outcomes, including preterm birth and stillbirth. Maternal vaccination provides direct protection to mothers by active immunisation
and to infants by passive immunisation. This scoping review mapped and described published literature on maternal vaccination against COVID-19, influenza, pertussis, and respiratory syncytial virus (RSV). It includes information on the outcome domains studied and if timing of vaccination was examined, with the aim of identifying evidence gaps and supporting decision-makers in choosing priority areas for subsequent systematic review topics. A comprehensive literature search across multiple databases of studies published from January 2000 to October 2025 identified 635 publications (540 publications of primary studies, 95 evidence syntheses). Studies on COVID-19 (260 publications of studies, 45 reviews), influenza (161 publications of studies, 29 reviews), pertussis (113 publications of studies, 20 reviews), and RSV (20 publications of studies, 11 reviews) were analysed. Available evidence on COVID-19, influenza, and pertussis vaccination on efficacy, effectiveness, safety and immunogenicity outcomes is considerable. RSV vaccination evidence is limited. Updated systematic reviews would be helpful to clarify the optimal timing of COVID-19 and influenza vaccination and the effectiveness and safety of the coadministration of influenza and pertussis vaccines.

Source: 

Link: https://www.nature.com/articles/s41541-026-01545-2

____

Substitutions affecting the HA–NA– #receptor #balance preceded the emergence of the #pandemic 2009 #H1N1 virus

 

Abstract

Swine are a crucial species in influenza A virus (IAV) ecology, capable of supporting replication and consequently evolution of human, avian, and swine strains. They are also the source of the 2009 pandemic H1N1 virus (H1N1pdm09). Understanding how swine IAV breach the species barrier is essential for detection of potentially pandemic viruses, but is often overlooked compared to avian IAV. We hypothesize that the HA–NA balance of (pre)pandemic swine viruses is a key feature that needs adjustment as swine and humans differ in their sialoglycome. We focused on a set of (pre)pandemic swine viruses collected in Mexico following the H1N1pdm09 emergence. Phylogenetic analysis showed that the emergence was preceded by substitutions in HA and NA predicted to affect their function. Thus, HA acquired substitution A227E, previously shown to reduce receptor binding in H1N1pdm09, while NA obtained substitution S369N in the 2nd sialic acid binding site (2SBS) predicted to reduce NA cleavage. The substitutions’ effect on the HA–NA balance, was confirmed with biolayer interferometry using recombinant proteins attached to nanoparticles. Engineering recombinant attenuated influenza viruses with swine HA and NA with/without the mentioned substitutions, showed that the 2SBS substitution negatively affected replication in primary human and swine cultures. Interestingly, replication was restored by the HA substitution. Overall, we show that the emergence of H1N1pdm09 in humans was preceded by substitutions in HA and NA that were acquired in swine and adjusted the HA–NA balance. We hypothesize that adjustment of the HA–NA balance was a critical step for crossing the host–species barrier.

Source: 

Link: https://doi.org/10.1073/pnas.2609870123

____

Molecular evolutionary #dynamics of #coxsackievirus A16 in #Shenzhen, #China, 2012–2022

 

Highlights

    • A decade of CV-A16 molecular epidemiology in Shenzhen was analyzed.

    • Bayesian methods estimated the molecular evolutionary rate of CV-A16.

    • Transmission risk and evolutionary dynamics of CV-A16 in Shenzhen were assessed.

Abstract

Objectives

To investigate the epidemiological and genetic characteristics of coxsackievirus A16 (CVA16) associated with hand, foot and mouth disease (HFMD) in Shenzhen, China.

Methods

CVA16 was examined by a real-time RT-PCR method. Complete VP1 gene sequences of CVA16 strains were determined, and sequence analyses were performed using a series of bioinformatics programs.

Results

Of 6436 mild HFMD specimens collected between 2012 and 2022, 1395 (21.7%) were CVA16-positive, with annual detection rates ranging from 4.1% to 45.4% and peaking in 2018. Molecular phylogenetic analysis revealed the circulation of three CVA16 sub-genotypes (B1a, B1b and B3) in Shenzhen, China. The major sub-genotype was B1b from 2013 to 2019, while the sub-genotype B1a predominated in 2020-2022. Phylogenetic and sequence homology analyses suggested that re-emerging CVA16 B1a strains in Shenzhen originated from Vietnam and Thailand. The mean evolutionary rate of CVA16 strains circulating in Shenzhen was estimated at 3.604×10-3 substitutions per site per year. Distinct amino acid mutations in VP1 correlated with temporal shifts in Shenzhen's dominant CVA16 sub-genotypes: N14S/L23M for B1b, and T164K/V251I for the 2017–2022 re-emergent B1a.

Conclusion

In the post-EV-A71 vaccine era, CVA16 remains one of the major pathogens of HFMD in Shenzhen. Over the study period, the CVA16 sub-genotype in Shenzhen underwent a B1a→B1b→B1a turnover, which was associated with both imported lineages and local adaptive evolution. This study underscores the critical importance of continuous molecular surveillance for CVA16.

Source: 

Link: https://doi.org/10.1016/j.jcv.2026.105998

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In silico analysis of #pH stabilising #mutations of #hemagglutinin of #influenza A virus #H5N1 clade 2.3.4.4b

 

Abstract

Highly pathogenic avian influenza A(H5N1) viruses are expanding their host range among mammals, raising concerns about their pandemic potential. Building on recently published deep mutational scanning data, we show that hemagglutinin retains structural plasticity to increase acid stability through independent mechanisms, including modulation of electrostatic interactions, hydrogen-bonding networks and hydrophobic packing that may facilitate human adaptation. These findings illustrate how structural analyses can strengthen genomic surveillance for pandemic risk assessment.

Source: 

Link: https://doi.org/10.1038/s44298-026-00236-y

____

Early insights into predicted efficacy of #Ebola monoclonal #antibodies for the 2026 #Bundibugyo virus disease #outbreak

 

Abstract

The 2026 Bundibugyo virus disease (BVD) outbreak in the DRC and Uganda raises urgent questions about the efficacy of existing Ebola virus (EBOV) monoclonal antibodies (mAbs) against Bundibugyo virus (BDBV). Here, we perform genomic and structural analyses of 44 BDBV sequences, including 12 from the 2026 outbreak, to assess mAb binding to the viral glycoprotein (GP). While the MBP134 cocktail epitopes remain conserved, mAb114 (Ebanga) binding is compromised by E112D and P116A mutations, causing off-target binding and reduced affinity. Structural modeling of Inmazeb shows that while Odesivimab maintains epitope binding, Atoltivimab and Maftivimab fail to bind their designated sites individually, though the complete trimeric cocktail demonstrates BDBV synergistic binding. These computational models predict mAb114 efficacy against BDBV may be compromised due to epitope mutations affecting binding affinity, whereas MBP134 retains conserved targeting and holds promise as a broadly protective therapeutic. The complex binding behavior of Inmazeb components points to the importance of antibody combinatorial effects for treatment efficacy. These observations warrant urgent experimental validation through neutralization assays.

Source: 

Link: https://doi.org/10.1038/s41467-026-78077-9

____

Highly Pathogenic Avian #Influenza Viruses #H5N1 and #H5N5 in Red #Foxes (Vulpes vulpes) in #Norway during 2022-2024

 

Abstract

Since 2020, highly pathogenic avian influenza (HPAI) A(H5Nx) clade 2.3.4.4b viruses have spread globally, causing extensive outbreaks in domestic and wild birds. Increased circulation has resulted in frequent spillover to mammals, and occasional mammal-to-mammal transmission. Although human infections remain rare, the zoonotic potential of these viruses continues to be a public health concern. We investigated six cases of HPAI in red foxes (Vulpes vulpes) in Norway during 2022-2024 and identified infections with H5N1 and H5N5 viruses. Pathological and virological investigations demonstrated systemic infection, with prominent lesions in the brain and/or lungs. Phylogenetic analyses showed high similarity between viruses detected in foxes and those concurrently circulating in wild birds. The mammalian adaptation marker PB2:E627K was identified in one H5N1 virus and as a minority variant in a second H5N1 virus.

Competing Interest Statement

The authors have declared no competing interest.

Funder Information Declared

Norwegian Veterinary Institute, 12314

Source: 

Link: https://doi.org/10.64898/2026.09.25.754393

____

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