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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Comparison of #Baloxavir-Based Combinations and Monotherapies for Treating #Influenza #H5N1 Clade 2.3.4.4b Virus #Infection in Mice

 

Abstract

Highly pathogenic avian influenza A(H5N1) clade 2.3.4.4b virus continues to cause animal outbreaks and sporadic zoonotic infections. In a mouse model of lethal influenza disease, we compared oseltamivir, baloxavir, and molnupiravir monotherapies with 2-drug combinations. Baloxavir-based combinations improved survival, reduced lung viral loads, and prevented extrapulmonary dissemination, supporting H5N1 preparedness strategies.

Source: 

Link: https://doi.org/10.3201/eid3210.260186

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#Global #framework to accelerate #action on avian #influenza (WOAH/FAO/WHO, September 21 '26, summary)

 

Required citation: FAO, WHO, WOAH and CMS. 2026. Global framework to  accelerate action on avian influenza. Rome. https://doi.org/10.4060/ce1712en

The designations employed and the presentation of material in this information product do not imply the expression

of any opinion whatsoever on the part of the Food and Agriculture Organization of the United Nations (FAO), the World

Health Organization (WHO), the World Organisation for Animal Health (WOAH) or the Convention on the Conservation of

Migratory Species of Wild Animals (CMS), concerning the legal or development status of any country, territory, city or area

or of its authorities, or concerning the delimitation of its frontiers or boundaries. The mention of specific companies or

products of manufacturers, whether or not these have been patented, does not imply that these have been endorsed or

recommended by FAO, WHO, WOAH or CMS in preference to others of a similar nature that are not mentioned.

The responsibility for the interpretation and use of the material lies with the reader, and in no event shall FAO, WHO,

WOAH or CMS be liable for damages arising from such interpretation or use.

ISBN 978-92-5-141028-8 [FAO]

ISBN (WHO) 978-92-4-012544-5 (electronic version)

ISBN (WHO) 978-92-4-012545-2 (print version)

© FAO, WHO and WOAH, 2026

Some rights reserved. This work is made available under the Creative Commons Attribution-NonCommercial-ShareAlike

3.0 IGO licence (CC BY-NC-SA 3.0 IGO; https://creativecommons.org/licenses/by-nc-sa/3.0/igo/ )

(...)

1. Introduction

Avian influenza is a complex global challenge with consequences for animal health,

human health, biodiversity, food security and livelihoods. In recent decades, high

pathogenicity avian influenza (HPAI) viruses have spread across continents, become

established in wild bird populations, affected an increasing range of mammalian species

and caused unprecedented impacts on wildlife, poultry production and associated

economies. These impacts are occurring alongside other environmental pressures

including climate change, habitat degradation and biodiversity loss.

Recognizing these challenges, the Food and Agriculture Organization of the United

Nations (FAO), the World Health Organization (WHO), the World Organisation for Animal

Health (WOAH) and the Convention on the Conservation of Migratory Species of Wild

Animals (CMS) have developed this global framework to strengthen collaboration on

avian influenza through a One Health approach.

This high-level framework is not intended to replace existing mandates, strategies or

technical guidance. Rather, it adds value by showing how existing mandates, strategies

and technical mechanisms can be better connected, aligned and communicated as part

of a shared One Health response to avian influenza. It reflects a recognition that no single

sector nor institution can address avian influenza alone, and that sustainable solutions

require coordinated efforts that integrate human, animal and environmental dimensions.

Developed through a participatory and consultative process, the framework draws

on the comparative strengths and roles of each organization (Figure 1). It emphasizes

the importance of human, domestic animal and wildlife surveillance, including in wild

birds, poultry and susceptible mammalian species, timely information and data sharing,

strong laboratory and workforce capacities, effective risk communication and sustained

investment in prevention and preparedness. It reinforces the principle that protecting

health is inseparable from protecting ecosystems and ensuring resilient agrifood systems.

Given the accelerating risks and impacts of avian influenza, there is an urgent need to

translate this framework into concrete action. This will require enhanced global support,

including increased and sustained investment in prevention, preparedness, surveillance,

mitigation and response capacities across sectors. The four organizations call on

governments, donors and partners to prioritize avian influenza within broader health

security and development agendas, and to mobilize the resources necessary to support

coordinated, country-led implementation of a One Health approach.

(...)

Source: 

Link: https://doi.org/10.4060/ce1712en

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Respiratory #pandemic #risk in the #Anthropocene: A #OneHealth #framework and #GISRS+ agenda

 

Highlights

    • Respiratory pandemics are now a structural feature of the Anthropocene.

    • H5Nx and SARS-related CoVs are identified as leading pandemic candidates.

    • A geographic mismatch exists between spillover risk and surveillance.

    • A multidimensional GISRS+ agenda is proposed for proactive One Health.

Abstract

Recent epidemics and pandemics caused by respiratory viruses, alongside the animal panzootic spread of highly pathogenic avian influenza A(H5Nx), have become a structural feature of the Anthropocene, yet responses remain largely reactive. This review integrates findings from WHO's Global Influenza Surveillance and Response System (GISRS) and related surveillance data (2000–2024), epidemiological studies of influenza A virus, SARS-CoV, MERS-CoV, SARS-CoV-2, and H5Nx, and One Health literature. We examine major groups of respiratory viruses and identify mismatches between risk and surveillance by focusing on spillover potential from animal hosts, human-to-human transmission and its controllability, and Anthropocene characteristics that increase epidemic risk. The analysis indicated that SARS-related coronaviruses and influenza A viruses, particularly H5Nx, are among the leading candidates based on currently available evidence because they have large reservoirs in animal hosts and spillover to humans is highly probable. The previous presymptomatic spread of SARS-CoV-2 and recent mammalian adaptation in H5N1 clade 2.3.4.4b highlight limitations of the traditional symptom-based and pathogen-specific surveillance system. Spillover events tend to occur in tropical and subtropical regions in low- and middle-income countries, but most genomic surveillance is in high-income countries. We propose interventions that address the upstream, midstream, downstream processes of epidemics. Upstream interventions are primary prevention measures related to land use, livestock, wildlife, and urban environments; midstream interventions are GISRS+-based pathogen-agnostic genomic and metagenomic early warning systems triggered by One Health; and downstream interventions include vaccines, antivirals, non-pharmaceutical interventions, and engineering with equity-centred global governance and sustainable financing.

Source: 

Link: https://doi.org/10.1016/j.onehlt.2026.101553

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Divergent #antibody-mediated population #immunity to #H5, #H7 and #H9 subtype potential #pandemic #influenza viruses

 

Abstract

Influenza continues to cause significant mortality globally and possesses substantial pandemic potential. Assessing pandemic risk requires a clear understanding of existing population immunity. Leveraging a unique large-scale cohort of human sera, we evaluated total and neutralising antibody-mediated immunity to multiple haemagglutinin (HA) proteins, including those from subtypes with high pandemic potential. Our analysis reveals that population immunity is heterogeneous, with distinct age-dependent differences in responses to H5, H7, and H9 avian influenza subtypes. These shifts align with historical circulation patterns of seasonal H1N1 and H3N2 human viruses. Notably, H7 viruses are primarily neutralised through head domain epitopes, while H5 viruses are targeted mainly via stem epitopes, although in both instances some neutralisation occurred via receptor binding site-adjacent epitopes. Furthermore, H7 responses were dominated by non-glycan-targeted IgG2 antibodies, whereas H5 responses were primarily IgG1-mediated. These findings highlight varying levels of susceptibility to influenza across the population, supporting vaccination approaches informed by exposure history.

Competing Interest Statement

CPT has received lecture fees from Moderna.

Source: 

Link: https://www.medrxiv.org/content/10.1101/2025.09.08.25335309v2

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#Safety, humoral and cellular immune responses to a pre-pandemic adjuvanted #influenza #H5N8 #vaccine

 

Abstract

Highly pathogenic avian influenza (HPAI) A(H5) viruses can be transmitted from infected birds to various mammalian species, including humans. Avian influenza viruses (AIVs), members of the Orthomyxoviridae family, possess segmented RNA genomes prone to reassortment, favoring the emergence of novel genetic traits that may alter transmissibility, pathogenicity, and antigenicity. Although no sustained human-to-human transmission has been reported, the potential adaptation of these viruses poses a significant pandemic threat. This study aimed to evaluate the non-clinical safety, toxicity, and humoral immune responses induced by an adjuvanted H5 influenza vaccine in rats and rabbits, to support future clinical safety trials in humans. Male and female Wistar rats and New Zealand rabbits were observed for 14, 28, and 90 days after receiving two intramuscular doses of the H5N8 vaccine (15 μg HA/dose) formulated with the IB160 oil-in-water emulsion adjuvant. No systemic comorbidities, central nervous system alterations, or relevant clinical signs were observed. Hematological parameters remained within normal ranges, with total and differential leukocyte counts showing only minor fluctuations (<1% of total leukocytes). Mild biochemical variations in urea and hepatic transaminase levels were not correlated with histopathological alterations. The vaccine elicited a robust humoral response soon after immunization, with all groups reaching protective HAI-antibody titers. Although antibody levels declined over time, particularly in males, they remained significantly above baseline, indicating durable immunological memory. Furthermore, the vaccine induced a specific cellular immune response, confirmed by IL-2 and TNF production by antigen-specific T lymphocytes in splenic cell cultures after the booster dose. In conclusion, the H5N8 vaccine with the IB160 adjuvant was well tolerated locally and systemically, without compromising vital organ function. The safety and immunogenicity findings are consistent with expectations for adjuvanted influenza vaccines, demonstrating strong and durable humoral and cellular immune responses.

Source: 

Link: https://www.sciencedirect.com/science/article/abs/pii/S0264410X26008583?via%3Dihub

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Lessons Learned During 2024‒25 Highly Pathogenic Avian #Influenza #H5N1 Virus #Outbreak Response in #USA: Experience of State and Local Public Health Departments

 

Abstract

Objectives. 

To describe challenges and lessons learned during state and local health department responses to the 2024‒2025 highly pathogenic avian influenza A(H5N1) outbreaks.

Methods. 

We conducted semistructured interviews from August to November 2025 with Department of Health and Agriculture staff from states with confirmed or probable A(H5N1) human cases. We conducted 15 total interviews with 37 participants from 10 US states. Interview transcripts were inductively and deductively coded to identify generalizable lessons that might improve future outbreak response efforts.

Results. 

Key themes included difficulty accessing farms and reaching at-risk populations; lack of sufficient guidelines for proactively responding to zoonotic outbreaks that could have human health implications; the importance of maintaining preparedness planning, capacity, and infrastructure; and uncertainty around future capacity to respond to outbreaks because of resource constraints and changes in federal leadership.

Conclusions. 

Although this study focused on responses to A(H5N1) outbreaks, the findings are indicative of the nation’s overall readiness for biological threats. Prioritization of capacity building for infectious disease outbreaks, including robust health department funding to support continued disease surveillance, is critical to prevent more widespread transmission. 

(Am J Public Health. Published online ahead of print September 3, 2026:e1–e7. https://doi.org/10.2105/AJPH.2026.308656)

Source: 

Link: https://ajph.aphapublications.org/doi/10.2105/AJPH.2026.308656

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Modeling the #impact of respiratory disease #outbreaks on the #US #agricultural #workforce

 

Abstract

Background: 

Emerging respiratory disease outbreaks pose a major threat to food production systems. Agricultural workers face health disparities that amplify their susceptibility to respiratory pathogens, yet the consequences for worker health and food production remain poorly understood. 

Methods: 

We developed a household-structured susceptible-infectious-recovered (SIR) transmission model to compare disease dynamics between agricultural workers and the general U.S. population across six regions. We simulated outbreaks across a range of epidemiological scenarios and assessed productivity losses in California for three labor-intensive crops (oranges, iceberg lettuce, strawberries) with different harvest seasonalities. 

Results: 

We show that, for a baseline reproduction number of R0 = 2.0, the peak disease prevalence among agricultural workers is 1.41-1.69 times higher than that of the general population across regions, and final outbreak sizes are 1.29-1.42 times higher. Household structure accounts for 54%-68% of the disease disparity. Peak productivity losses range from 0.50%-0.63% across crops, translating to millions in lost potential revenue. At higher transmissibility and severity (R0 = 3 and assuming all infections are symptomatic), losses are 2.4 times higher. 

Conclusions: 

Household crowding may lead to disproportionate respiratory disease burden among agricultural workers that is exacerbated by vaccination and obesity disparities, highlighting the need for targeted outbreak preparedness and mitigation strategies in the agricultural sector to maintain food system resilience and support public health in these communities.

Competing Interest Statement

The authors have declared no competing interest.

Source: 

Link: https://www.medrxiv.org/content/10.64898/2026.03.31.26349871v2

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A novel candidate #vaccine virus derived from #Japan's first #mammalian case of clade 2.3.4.4b #H5N1 highly pathogenic avian #influenza virus

 

Abstract

The development of candidate vaccine viruses (CVVs) for pre-pandemic preparedness requires attenuation of pathogenicity while maintaining immunogenicity. In this study, we developed and characterized NIID-002, a reassortant virus derived from A/Ezo red fox/Hokkaido/1/2022 (H5N1; clade 2.3.4.4b), to evaluate its suitability as a candidate vaccine. NIID-002 exhibited markedly reduced pathogenicity compared with its parental strain, while retaining broad antigenic reactivity and protein yield comparable to other clade 2.3.4.4b CVVs. In mammalian models, NIID-002 demonstrated strong attenuation, causing no lethal infection in mice and only minimal weight loss with limited viral replication in ferrets. Antisera raised against NIID-002 reacted broadly with recent wild-type H5N1 isolates, suggesting potential broad protection. Protein yield analysis confirmed a production efficiency comparable to that of other CVVs within the same clade, supporting its feasibility for large-scale vaccine manufacturing. Overall, NIID-002 fulfills the key requirements for the pandemic preparedness of CVV, combining reduced pathogenicity, broad antigenic reactivity, and adequate production efficiency. These findings highlight its potential as a candidate H5N1 vaccine and underscore the continued need for surveillance and refinement of influenza vaccine strategies to address evolving viral threats.

Source: 

Link: https://www.sciencedirect.com/science/article/abs/pii/S0264410X26008571?via%3Dihub

____

#Community #engagement strategies for preventing recurrent #Nipah virus #outbreaks in #Bangladesh and #India: adapting a framework for outbreak preparedness and response

 

Abstract

The Nipah virus (NiV) infection is a highly fatal zoonotic disease with pandemic potential which has led to recurrent outbreaks in Bangladesh and India. While transmission pathways, including contaminated date palm sap and human-to-human spread, are increasingly identified, significant uncertainties remain. With no approved therapeutics or vaccines, prevention depends on addressing ecological and behavioural drivers of transmission. This viewpoint draws on selected evidence from NiV outbreaks and response to other zoonotic disease epidemics, such as Ebola, rabies, and the Marburg virus disease, we seek to foster discussion on why community engagement could be central to NiV prevention and preparedness. We highlight the relevance of community engagement through a spectrum of its intensity, which distinguishes between community-oriented, community-based, community-managed, and community-owned approaches. Adapting an existing model, we discuss how community engagement principles can be applied to tackle recurring NiV outbreaks in Bangladesh and India. By aligning interventions with sociocultural realities, community engagement can improve acceptability, enhance early detection, strengthen outbreak response, and support preparedness for future vaccine and therapeutic research. However, evidence specific to NiV remains limited and lessons from other diseases should be applied judiciously. In the absence of medical countermeasures, participatory, locally grounded approaches offer a sustainable pathway to reduce recurrent outbreaks and prevent future spillover events.

Source: 

Link: https://jogh.org/2026/jogh-16-03024

____

Enhanced #Pathogenicity and Contact #Transmissibility of #Human-origin Avian #Influenza #H5N1 Clade 2.3.4.4b Genotype B3.13 Compared to D1.1 in #Ferrets

 

Abstract

Since its emergence in 2020, multiple genotypes of the H5N1 clade 2.3.4.4b have been identified, with B3.13 and D1.1 emerging in the USA as two major and concerning genotypes. However, their relative pathogenicity and transmissibility in mammals have not been fully elucidated. We compared the pathogenicity and transmissibility of the first two human H5N1 clade 2.3.4.4b cases caused by B3.13 in Texas (A/Texas/37/2024; HPhTX B3.13) and D1.1 in Louisiana (A/Louisiana/12/2024; HPhLA D1.1) in a ferret model of infection and transmission. HPhTX B3.13 infection resulted in more severe clinical disease and enhanced viral shedding, with evidence of increased transmission relative to HPhLA D1.1. Histopathological analysis revealed more extensive lung pathology in animals infected with HPhTX B3.13, consistent with increased viral loads and inflammatory responses. Importantly, both genotypes showed no significant differences in reactivity to ferret sera raised against candidate vaccine virus (CVV) strains, receptor binding properties, or neuraminidase (NA) activity and thermostability. Whole-genome sequencing revealed no adaptive mutations in HPhTX B3.13 following infection or transmission. In contrast, HPhLA D1.1 showed rapid acquisition of the mammalian-adaptive mutation E627K in infected ferrets and both E627K and Q194K in the only fatal contact animal. Both mutations were associated with enhanced polymerase activity and computational analyses suggested that they enhance interactions with the mammalian host factors ANP32A and B. Our findings indicate that B3.13 is already well adapted for mammalian infection and transmission whereas D1.1 retains evolutionary potential through the rapid acquisition of adaptive mutations, highlighting important genotype-specific differences relevant to zoonotic risk assessment and pandemic preparedness.

Competing Interest Statement

The A.G.-S. laboratory has received research support from Avimex, Dynavax, Pharmamar, and Accurius, outside of the reported work within the last three years. A.G.-S. has consulting agreements for the following companies involving cash and/or stock within the last three years: Castlevax, Amovir, Vivaldi Biosciences, Contrafect, Avimex, Pagoda, Accurius, Applied Biological Laboratories, Pharmamar, CureLab Oncology, CureLab Veterinary, Virofend, Prosetta and A.A.C.T., outside of the reported work. A.G.-S. has been an invited speaker in meeting events within the last three years organized by Seqirus, Novavax and Hipra. A.G.-S. is inventor on patents and patent applications on the use of antivirals and vaccines for the treatment and prevention of virus infections and cancer, owned by the Icahn School of Medicine at Mount Sinai, New York, outside of the reported work. The Icahn School of Medicine at Mount Sinai has licensed some of these inventions to Medimmune, Avimex, Leinco Technologies, Castlevax, Virofend, Kerafast, Cell Signaling, EMD Millipore, Genentech, Paratus and Nura Bio, and as a result receives financial compensation. Subject to Mount Sinai receiving such financial consideration, AG-S will receive a portion of that consideration pursuant to the terms of the Mount Sinai Intellectual Property Policy. All other authors declare no commercial or financial conflict of interest.

Funder Information Declared

NIH/NIAID, 75N93021C00014

Horizon Europe Program, KAPPA-FLU no. 101084171

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.08.10.744032v1

____

Protective effect of #H5N8 stockpiled #vaccine against a virus genetically identical to a #human isolate of #bovine #H5N1 #influenza virus

 

Summary

Background

Since early 2024, highly pathogenic avian influenza A(H5N1) viruses of clade 2.3.4.4b have caused extensive outbreaks in dairy cattle in the United States, with spillover into mammalian species, including humans. A bovine-derived A(H5N1) virus isolated from a human case retains high pathogenicity and transmissibility in mammalian models, highlighting its pandemic potential. Stockpiled pre-pandemic influenza vaccines are intended to provide early protection before strain-matched vaccines are available; however, their protective efficacy against bovine A(H5N1) viruses has not been directly evaluated in vivo.

Methods

In this study, we assessed the protective efficacy of an AS03-adjuvanted A/Astrakhan/3212/2020 (H5N8) clade 2.3.4.4b-based influenza vaccine stockpiled in Japan using mouse and ferret models. Vaccinated and unvaccinated animals were challenged with a virus genetically identical to a human isolate of bovine A(H5N1) virus. Neutralising antibody responses, viral replication in organs, and survival were evaluated.

Findings

Vaccination with the AS03-adjuvanted A(H5N8)-based stockpiled vaccine induced robust neutralising antibody responses in both animal models, significantly suppressed viral replication, and conferred complete protection against lethal challenge. In contrast, all unvaccinated mice and ferrets succumbed to infection. These findings demonstrate that the AS03-adjuvanted A(H5N8)-based stockpiled vaccine provides strong cross-protective efficacy against bovine A(H5N1) viruses.

Interpretation

An AS03-adjuvanted A(H5N8)-based vaccine stockpiled in Japan could serve as an immediate countermeasure against bovine A(H5N1) viruses during the early phase of a pandemic.

Funding

This work was supported by grants from the Japan Program for Infectious Diseases Research and Infrastructure (JP20wm0125002) and the Japan Initiative for World-leading Vaccine Research and Development Centers (JP223fa627001) from the Japan Agency for Medical Research and Development.

Source: 

Link: https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(26)00314-2/fulltext

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Heterologous prime-boost #vaccination against #H5 avian #influenza: Safety and immunogenicity of a MF59-adjuvanted, cell-culture derived #H5N6 vaccine

 

ABSTRACT

With increasing H5 avian influenza cases reported globally and the potential for pandemic emergence, induction of cross-reactive antibody responses may represent an important attribute of an effective vaccine. This phase 2 extension study evaluated immunogenicity and safety of MF59-adjuvanted, cell culture-derived H5N6 vaccine (aH5N6c) in adults primed with MF59-adjuvanted, cell culture-derived H5N1 vaccine (aH5N1c) and in unprimed adults. Adults previously primed with two doses of aH5N1c in the parent study V89_18 were randomized to receive two aH5N6c doses (Group 1) or one aH5N6c and one placebo (Group 2) 3 weeks apart. Unprimed adults received two aH5N6c doses (Group 3). Immunogenicity was assessed by hemagglutination inhibition (HI) and microneutralization (MN) assays against the priming (H5N1) and booster (H5N6) strains on Days 1, 8, 22, 43, and 202. Among 258 exposed participants, primed subjects (Groups 1 and 2) showed higher HI geometric mean titers against both strains than unprimed (Group 3) subjects, with MN responses similarly enhanced. Heterologous H5N1 responses were robust in primed subjects (Day 43 HI GMTs: 333–343; seroconversion rates >89%) but minimal in unprimed subjects, with responses persisting to Day 202. Solicited adverse events were mild or moderate, comparable between groups, and consistent with other MF59-adjuvanted pandemic vaccines; no vaccine-related serious adverse events occurred. Heterologous H5N6 booster vaccination in H5N1-primed adults elicited strong cross-reactive immunity against the priming strain, demonstrating long-lasting immune memory for at least 6 y and supporting heterologous prime-boost strategies for pandemic preparedness against emerging H5 outbreaks.

Source: 

Link: https://www.tandfonline.com/doi/full/10.1080/21645515.2026.2712791

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A One-Shot Multivalent Live-Attenuated Candidate #Influenza #Vaccine against Divergent #Zoonotic #H5N1 Clades

 

Abstract

The continued emergence of genetically diverse high pathogenicity avian influenza (HPAI) H5N1 viruses with zoonotic potential highlights the urgent need for developing vaccines capable of providing broad protection against multiple circulating clades. Here, we developed a one-shot, multivalent, live-attenuated influenza vaccine (LAIV) based on the temperature-sensitive (ts), cold-adapted (ca), and attenuated (att) influenza A/Ann Arbor/6/1960 master donor virus (MDV) that incorporates the hemagglutinin (HA) and neuraminidase (NA) glycoproteins from representative clades 2.3.4.4b (A/Louisiana/12/2024), 2.3.2.1a (A/Victoria/149/2024), and 2.3.2.1e (A/Cambodia/2302009/2023) H5N1 viruses. A single intranasal (IN) immunization of C57BL/6 mice with the multivalent LAIV elicited robust humoral immune responses, with immune sera exhibiting broad cross-reactivity against antigens from all three H5N1 clades included in the vaccine. Following homologous viral challenge, vaccinated C57BL/6 mice were completely protected from disease, demonstrating the immunogenicity and protective efficacy of the multivalent LAIV. By simultaneously targeting antigenically distinct H5N1 lineages with pandemic potential, this strategy expands antigenic coverage within a single LAIV to confirm pan-H5N1 protection. Together, these findings support the development and implementation of this multivalent LAIV as a broadly protective pan-H5N1 LAIV for pandemic preparedness.

Competing Interest Statement

The A.G.-S. laboratory has received research support from Avimex, Dynavax, Pharmamar, and Accurius, outside of the reported work within the last three years. A.G.-S. has consulting agreements for the following companies involving cash and/or stock within the last three years: Castlevax, Amovir, Vivaldi Biosciences, Contrafect, Avimex, Pagoda, Accurius, Applied Biological Laboratories, Pharmamar, CureLab Oncology, CureLab Veterinary, Virofend, Prosetta and A.A.C.T., outside of the reported work. A.G.-S. has been an invited speaker in meeting events within the last three years organized by Seqirus, Novavax and Hipra. A.G.-S. is inventor on patents and patent applications on the use of antivirals and vaccines for the treatment and prevention of virus infections and cancer, owned by the Icahn School of Medicine at Mount Sinai, New York, outside of the reported work. The Icahn School of Medicine at Mount Sinai has licensed some of these inventions to Medimmune, Avimex, Leinco Technologies, Castlevax, Virofend, Kerafast, Cell Signaling, EMD Millipore, Genentech, Paratus and Nura Bio, and as a result receives financial compensation. Subject to Mount Sinai receiving such financial consideration, AG-S will receive a portion of that consideration pursuant to the terms of the Mount Sinai Intellectual Property Policy. All other authors declare no commercial or financial conflict of interest.

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.08.02.742385v1

____

#Spain, Ministry of Health is strengthening #prevention, #preparedness and response to #animal-borne #influenza with a national plan (Min. Health, July 16 '26)

 

    Madrid, July 16, 2026.- The Public Health Commission has approved the State Plan against infections by influenza viruses of zoonotic origin: Prevention, Surveillance and Control, which establishes a common framework for prevention, surveillance, early detection and response to influenza viruses that circulate in animals and can be transmitted to people.

    The Plan adopts the "One Health" approach and establishes a joint response across the fields of human health, animal health, and the environment. Its objective is to improve coordination among the different sectors at the national, regional, and local levels, and to ensure that epidemiological, microbiological, and environmental information is integrated, up-to-date, and readily available to facilitate the early implementation of control measures.

    The document has been coordinated by the Center for Coordination of Health Alerts and Emergencies (CCAES) of the Ministry of Health and prepared jointly with the Ministries of Agriculture, Fisheries and Food and for Ecological Transition and the Demographic Challenge, the Carlos III Health Institute, the Spanish Agency for Food Safety and Nutrition and other units involved in the prevention and management of these risks.

    Zoonotic influenza viruses circulate among animals. Transmission to humans remains infrequent and is usually linked to direct contact with infected animals, their secretions, or contaminated environments. However, their ability to mutate and exchange genetic material necessitates continuous surveillance, especially given the increased detection of these viruses in various mammal species.

    The Plan organizes the actions into four scenarios , which allow the measures to be progressively adapted to the epidemiological situation of each territory.

    Scenario 0 corresponds to a situation with no detected infections in animals or people and focuses on ordinary actions of prevention, surveillance, training and maintenance of diagnostic capabilities.

    Scenario 1 is activated upon detection of outbreaks in wild or captive animals. It distinguishes between isolated outbreaks in birds, multiple outbreaks distributed across a territory, and detections in wild mammals.

    Scenario 2 considers outbreaks in domestic animals and also differentiates between isolated outbreaks in birds, multiple outbreaks, and detections in domestic mammals.

    Finally, scenario 3 applies when a human infection is identified. In this case, a distinction is made between cases with known exposure to animals or contaminated environments, those where no risk exposure is identified, and cases associated with contact with another infected person, which would imply possible limited human-to-human transmission.

    The scenarios are not mutually exclusive and may be applied simultaneously in the same territory. Each autonomous community will conduct its own risk assessment to determine the necessary measures in each affected province, community, or geographical area.

    The Plan envisions the creation of a Permanent State Committee for Coordination and Monitoring , chaired and technically coordinated by the CCAES, responsible for reviewing preparedness and response measures, promoting common protocols, conducting joint risk assessments, and evaluating the Plan's effectiveness. Furthermore, it recommends that the autonomous communities establish equivalent bodies to coordinate actions related to public health, animal health, the environment, food safety, and occupational health.

    This body will include representatives from the competent departments in public health, animal health, biodiversity, food safety, occupational health, medicines and health products and epidemiological and microbiological surveillance, as well as from the autonomous communities, the Spanish Federation of Municipalities and Provinces and experts.

    Human health measures focus especially on people who, due to their professional activity, may come into contact with infected animals, their secretions or contaminated materials, such as livestock farm personnel, veterinary professionals, environmental agents or zoo workers.

    Companies must assess the risk, provide the necessary protective equipment, and ensure health monitoring. Occupational risk prevention services will identify and monitor exposed personnel in the event of outbreaks in animals and, where appropriate, may recommend PCR tests, preventive antiviral treatment, or vaccination against zoonotic viruses.

    The Plan also maintains the recommendation for seasonal flu vaccination for those who work in direct contact with animals, with the aim of reducing the risk of coinfection by human and animal flu viruses.

    In the animal sector , the Plan strengthens surveillance of wild and domestic birds and mammals, as well as genomic analysis of viruses to detect changes that could increase their transmissibility. In the event of outbreaks on farms, biosecurity measures, movement controls, confinement, and, where appropriate, vaccination will be implemented.

    In parks and urban or peri-urban areas, protocols will be established to safely remove sick or dead animals, clean and disinfect affected areas, and inform the public. It is recommended not to touch or handle them and to report their presence to the appropriate authorities.

    The Plan incorporates risk communication and community participation as one of its five main components. To this end, an inter-institutional communication group will be established, websites with updated information will be created, and campaigns will be developed targeting both the general public and the professional sectors with the greatest exposure.

    Media and social media will also be monitored to detect and respond to rumors, false content, or unverified information. In higher-risk scenarios, an official spokesperson will be appointed, information will be updated daily, and, when necessary, a citizen hotline will be activated.

    The Permanent State Committee will develop the indicators that will allow the evaluation of preparedness and response, as well as compliance with the Plan in its various components and at the state and regional levels.

    In the last year, more than 150 outbreaks of avian influenza have been detected in Spain, mostly in wild birds, although outbreaks have also been recorded in poultry, leading to the culling of thousands of animals. Despite the increased circulation of the virus among birds, Spain has not registered any human cases of avian influenza to date. Regarding swine influenza, three human cases of infection have been identified in Spain since 2009.

    The new Plan will strengthen prevention, early detection and coordinated response to any changes in the epidemiological situation.

Source: 

Link: https://www.sanidad.gob.es/gabinete/notasPrensa.do?id=6965

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Occupationally Exposed and General #Population #Antibody #Profiles to #Influenza A Viruses Circulating in #Swine as Indication of Zoonotic #Risk

 

Abstract

Persons with occupational exposure to swine might be at disproportionate risk for zoonotic swine influenza A virus. To evaluate human antibody responses, we tested serum or plasma from swine veterinarian, farm employee, and general population cohorts by hemagglutination inhibition assays against representative swine and human seasonal influenza vaccine strains. We analyzed hemagglutination inhibition data by antigenic cartography to assess strain relationships and reproduction number modeling to evaluate pandemic potential using age-stratified immunity profiles. Occupationally exposed groups had lower human seasonal vaccine uptake (45.5% vs. 70%) and lower odds of seropositivity to several H1 and H3 strains from swine than did general population cohorts. One swine strain exhibited significant antigenic drift (3.62 antigenic units) from its nearest vaccine strain. Multiple strains required lower reproduction number thresholds for pandemic spread (1.09–1.35) than recorded pandemic strains (1.46–1.80), demonstrating that population immunity gaps heighten zoonotic risk to circulating swine H1 and H3 strains.

Source: 

Link: https://wwwnc.cdc.gov/eid/article/32/8/25-1995_article

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Preparing for the Next #Pandemic: Learning From #COVID19 to Build What Comes Next

 

Abstract

WHO's efforts to strengthen pandemic preparedness—grounded in what the world learned during COVID-19 and what today's outbreaks of avian influenza, Hantavirus and Ebola are teaching us.

Source: 

Link: https://academic.oup.com/ofid/article/13/7/ofag348/8728458

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Immunoinformatics-Guided Design and In Silico Evaluation of a Multi-Epitope #Vaccine Against #Influenza A #H10N5 and #H3N2 Strains Based on HA and NA Proteins

 

Abstract

Influenza A viruses H3N2 and H10N5 represent, respectively, a persistently dominant seasonal pathogen and a newly documented zoonotic threat with the latter strain variants responsible for the first confirmed human fatality in January 2024, yet no vaccine platform currently addresses co-protection against both subtypes within a unified immunogen. We report here the immunoinformatics based vaccine design and multi-layered computational validation of a 419-amino-acid multi-epitope subunit vaccine construct targeting conserved hemagglutinin (HA) and neuraminidase (NA) antigens identified through multiple sequence alignment of the avian H10N5 (A/swine/Hubei/10/2008) and H3N2 human reference strain sequences to identify viral agents undergoing mammalian adaptations. Linear B-cell, cytotoxic T lymphocyte (CTL), and helper T lymphocyte (HTL) epitopes were predicted using ABCpred, BCEpred, BepiPred 2.0, NetMHCpan 2.1, and NetMHCpan 4.0, then filtered through VaxiJen 3.0, AllerTOP v2.1, and ToxinPred to retain only antigenic, non-allergenic, non-toxic candidates. The final construct, incorporating an avian β-defensin N-terminal adjuvant with GPGPG, AAY, and EAAAK linkers, exhibited a molecular weight of 43.9 kDa, instability index of 31.15, and SOLPro solubility probability of 0.763. Tertiary structure modeling via I-TASSER and GalaxyRefine achieved 84.4% Ramachandran-favored residues. Molecular docking against TLR3 and TLR7 yielded binding free energies of −16.1 and −16.8 kcal/mol with picomolar dissociation constants. Molecular dynamics simulations confirmed complex stability over extended trajectories. Furthermore, codon optimization produced a Codon Adaptation Index of 1.0 for E. coli K12 expression. In silico immune simulation demonstrated robust activation of humoral and cellular immunity including elevated IgG1, IgM, IFN-γ, IL-2, rapid NK cell expansion, and broad B-cell clonal diversity. These findings establish a computationally validated candidate capable of providing protection against influenza in multiple host organisms, warranting experimental advancement.

Competing Interest Statement

The authors have declared no competing interest.

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.07.03.736294v1

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#Vaccine #strategies and #development before and during the 1968 #H3N2 #influenza #pandemic

 

Abstract

Nearly 60 years ago, in 1968, the global population was confronted with the emerging pandemic influenza A virus (IAV) subtype H3N2 (1968 H3N2pdm). An estimate of up to two million fatalities have been linked to 1968 H3N2pdm, and the H3N2 subtype continues to circulate as seasonal IAV among humans until today. The last IAV pandemic dates back to the year 2009 but concerns about a new IAV pandemic in the near future are increasing. The global spread of H5N1 highly pathogenic avian influenza virus and its spill-over into new mammalian hosts, discovery of novel influenza A virus with zoonotic or even pandemic potential, as well as seasonal influenza viruses undergoing antigenic changes necessitate constant vigilance. Here, we highlight the proactive actions, precautionary measures and vaccination strategies used during the 1968 H3N2 IAV pandemic. Our review highlights the emergence and spread of 1968 H3N2pdm over the course of the pandemic, alongside a delineation of vaccine development before, during and after the 1968 pandemic. Updating these strategies in the context of new findings combined with our experiences during the coronavirus disease 2019 (COVID-19) pandemic is necessary to improve preparedness for the next pandemic. Influenza viruses with zoonotic potential will remain a constant threat to public health, and improving countermeasures and communication to the public is key to limit the pandemic ramifications.

Source: 

Link: https://www.sciencedirect.com/science/article/abs/pii/S0264410X26006869?via%3Dihub

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#Andes Virus on a Cruise #Ship, what it Tells us About the #Global #Pandemic #Preparedness Agenda

 

Summary

The outbreak of hantavirus disease caused by Andes virus aboard a cruise ship is a reminder of the challenges posed by emerging diseases in the modern era. While Andes virus-associated disease can be particularly severe, it is unlikely to spread extensively beyond the current number of cases or emerge as a large epidemic, especially if public health measures are followed. Nonetheless, the outbreak exemplifies the complexity of international outbreak response with differences in national preparedness frameworks and the rapid spread of mis-/disinformation. We discuss this outbreak in the context of global epidemic and pandemic preparedness and emphasize the importance of sustained, inclusive global collaborative One Health approaches to preparedness and response. We stress the urgent need for global coordination, discuss specific challenges, and provide recommendations for further strengthening of global preparedness.

Source: 

Link: https://www.thelancet.com/journals/lanepe/article/PIIS2666-7762(26)00167-5/fulltext

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