An ultrapotent #human #antibody neutralizes all maturation states of #Zika virus

 

Significance

Zika virus causes microcephaly in fetuses and no vaccines or therapeutics currently exist against it. Mature and immature flavivirus particles are infectious. Here, we showed the cryoelectron microscopy (cryoEM) structures of an ultrapotent A9E human antibody, complexed with both mature (mZIKV) and immature (immZIKV) Zika virus, and the antibody neutralization mechanism. One important characteristic is that Fab A9E can distort both mZIKV and ImmZIKV particle structures. Additionally, Fab A9E or IgG A9E LALA mutant can abolish or reduce the overall infection to myeloid cells when added to other infection enhancing antibody DV62.5:immZIKV complexes. Thus, antibody A9E represents a promising potential prophylactic and therapeutic candidate, as it is effective against all maturation states of Zika virus.

Abstract

Zika virus (ZIKV), a flavivirus, causes a range of clinical complications including microcephaly in human fetuses. Currently, there is no treatment or vaccine. Different maturation states (mature and immature forms) of flavivirus particles have been observed to be released from infected cells and are infectious. To understand how an ultrapotent human antibody (HMAb) A9E can neutralize these Zika particles, we determined the cryoEM structures of the A9E Fab fragment complexed with mature (mZIKV) and immature (immZIKV) ZIKV to 2.8Å and 7.5Å, respectively. A9E binds to an epitope spanning Domain I (EDI), EDIII, and their linker in an E protein protomer in both immZIKV and mZIKV particles. A9E generally inhibited prior to or during virus attachment to cells, via virus aggregation, distortion of virus particles and inhibition of receptor binding. ImmZIKV is particularly sensitive to structural distortion by Fab A9E. The primary mode of infection used by ImmZIKV is via antibody-dependent enhancement of infection (ADE)—the formation of virus complex with nonneutralizing or subneutralizing concentrations of antibodies, that leads to enhanced infection of Fcγ positive myeloid cells. IgG A9E, by itself displays poor ADE activity. When IgG LALA mutant or Fab A9E is added to other enhancing antibody (DV62.5):virus complexes, they can strongly reduce the overall ADE activity. This is likely due to their ability to distort virus particle structure, suggesting that HMAb A9E could be a potential prophylactic and therapeutic candidate against all maturation states of ZIKV.

Source: 

Link: https://www.pnas.org/doi/abs/10.1073/pnas.2502522122?af=R

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Expanding Horizons: #Host Range #Evolution and #Treatment Strategies for Highly Pathogenic Avian #Influenza #H5N1 and #H7N9

 

Abstract

Avian influenza viruses (AIVs), including H5N1 and H7N9, from the Orthomyxoviridae family present substantial public health concerns. The predominant circulating clade 2.3.4.4b has demonstrated enhanced capacity for mammalian adaptation, raising concerns about potential reassortment with human seasonal influenza viruses. Unlike H7N9’s limited host range, H5N1 infects birds, various mammals, and humans. Recent concerns include widespread H5N1 infection of U.S. dairy cattle across 18 states, affecting over 1000 herds with 71 human infections (70 H5N1 and 1 H5N5). Key observations include cow-to-cow transmission, viral presence in milk, and transmission to humans, mainly through occupational exposure. Evidence of mammal-to-mammal transmission has been documented in European and Canadian foxes and South American marine mammals. Standard pasteurization effectively inactivates the virus in milk. The continuing mammalian adaptations, particularly mutations like PB2-E627K, PB2-D701N, and PB2-M535I, suggest potential for further evolution in new hosts, emphasizing the need for enhanced surveillance to mitigate pandemic risks.

Source: 

Link: https://www.mdpi.com/1999-4915/18/1/54

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Phylogenetic Characteristics and High Prevalence of a #Merbecovirus in #Hedgehogs from Greenspace of a Metropolis, #China

 

Abstract

SARS-CoV, MERS-CoV, and SARS-CoV-2 have posed tremendous threats to human health, highlighting the necessity of monitoring cross-species transmission of animal coronaviruses to humans. Hedgehogs infected with coronaviruses have been reported in several countries across Europe and Asia, raising concerns about the potential transmission of coronaviruses from hedgehogs to humans. In this study, we investigated coronavirus infections in hedgehogs inhabiting greenspaces in metropolitan Beijing and identified a Merbecovirus subgenus coronavirus with a prevalence rate of 30% (95% CI: 25–35%) among 317 hedgehogs. Phylogenetic analysis of 23 complete viral genome sequences revealed a monophyletic origin, showing close relatedness to Erinaceus hedgehog coronavirus HKU31 (Ea-HedCoV HKU31) with genome-wide nucleotide identities of 93.24–96.42%, and evidence of recombination with Tylonycteris bat coronavirus HKU4. These findings suggest that the increase in wildlife populations associated with urban greenspace development may pose a potential threat to human health that should not be overlooked.

Source: 

Link: https://www.mdpi.com/2076-2607/14/1/83

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PA-X 122V broadly determines the #host shutoff #activity of #influenza A viruses

 

ABSTRACT

Multiple genes are involved in the pathogenicity of influenza A virus. Our previous study reported two naturally occurring amino acid mutations in the polymerase acidic (PA) protein as crucial determinants of the virulence of Eurasian avian-like H1N1 (EA H1N1) influenza viruses. PA-X, an accessory protein encoded by the PA gene, is thought to play a role in viral pathogenicity and regulation of host immune response, but its specific function remains unclear. In this study, we found that two genetically similar EA H1N1 influenza viruses, A/swine/Liaoning/FX38/2017 (FX38) and A/swine/Liaoning/SY72/2018 (SY72), induced significantly different suppression levels of host protein synthesis. The difference in host shutoff activity induced by PA-X protein was the key factor affecting the inhibition of host gene expression. Loss of PA-X expression significantly reduced its host shutoff activity, thereby enhancing host antiviral immune response. PA-X deficiency had no apparent effect on polymerase activity or replication capacity. We pinpointed a single residue 122V involved in the ability of PA-X to inhibit host gene expression and thereby modulate the host antiviral response. Notably, PA-X 122V was highly conserved among multiple subtypes of influenza A viruses and vital for maintaining the inhibitory effects on the host protein synthesis. Together, these findings demonstrate that the PA-X protein plays a major role in the suppression of host protein synthesis during influenza virus infection and elucidate the molecular mechanism by which the amino acid residue 122V in PA-X facilitates its suppression effects on host innate immune responses.

Source: 

Link: https://journals.asm.org/doi/full/10.1128/mbio.03433-25?af=R

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#USA, #Wastewater Data for Avian #Influenza #H5 (#CDC, Dec. 30 '25)

 

{Excerpt}

Time Period: December 14, 2025 - December 20, 2025

-- H5 Detection: 1 site(s) (0.2%)

-- No Detection: 461 site(s) (99.8%)

-- No samples in last week: 57 site(s)

(...)

Source: 

Link: https://www.cdc.gov/nwss/rv/wwd-h5.html

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#Finland - #Influenza A #H5 viruses of high pathogenicity (Inf. with) (non-poultry including wild birds) (2017-) - Immediate notification [FINAL]

 

A Whooper Swan in Lounais-Suomen aluehallintovirasto Region.

Source: 

Link: https://wahis.woah.org/#/in-review/7156

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Quantifying #H5N1 #outbreak #potential and #control effectiveness in high-risk agricultural populations

 

Abstract

Avian influenza is a global public health threat. Since 2021, the ongoing H5N1 panzootic has brought a major shift in H5Nx epidemiology, including unprecedented spread, wide host range and lack of seasonality. Infections in marine mammals, wildlife and livestock have heightened concern for human-to-human transmission and pandemic potential. Contact tracing and self-isolation are used as public health measures in the UK to manage contacts of confirmed human cases of avian influenza. In this study, we aimed to estimate potential outbreak sizes and evaluate the effectiveness of contact tracing and self-isolation in managing community outbreaks of H5N1 following spillover from birds to people. We characterised contact patterns from an underrepresented agricultural population at high risk of avian influenza exposure through contact with birds (Avian Contact Study). Informed by these realistic social contact data, we modelled outbreak sizes using a stochastic branching process model. Most simulations resulted in small-scale outbreaks, ranging from 0 to 10 cases. When the basic reproduction number was 1.1, contact tracing and self-isolation reduced the average outbreak size from 41 cases (95% Confidence Interval (CI): 37–46 cases) to 7 cases (95% CI: 6–8 cases), preventing, on average, 8 out of every 10 infections. However, controls became less effective in reducing the outbreak size when a higher proportion of cases were asymptomatic. Overall, our findings suggest that contact tracing and self-isolation can be effective at preventing zoonotic infections. Increasing awareness, encouraging self-isolation, and detecting asymptomatic cases through routine surveillance are important components of zoonotic infection containment strategies.

Source: 

Link: https://journals.plos.org/globalpublichealth/article?id=10.1371/journal.pgph.0005463

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Serological and viral #prevalence of #Oropouche virus (OROV): A systematic review and meta-analysis from 2000–24 including #human, #animal, and #vector #surveillance studies

 

Abstract

Background

Oropouche virus (OROV) is an emerging arbovirus primarily transmitted by biting midges and is increasingly recognized as a public health threat in Central and South America. With over 11,000 confirmed cases reported in 2024, a ten-fold increase from the previous year, its transmission dynamics and true burden remain poorly understood due to diagnostic challenges and fragmented surveillance systems.

Objective

This systematic review and meta-analysis (SRMA) synthesizes OROV prevalence data in humans and summarizes the available data for vectors and animal hosts sampled between 2000 and 2024 to provide updated estimates and identify key surveillance gaps.

Methods

We systematically searched Web of Science, PubMed, Embase, Medline, and LILACS for OROV seroprevalence and viral prevalence studies in human, insect, and animal populations, published up to September 12, 2024. The review protocol was registered with PROSPERO (CRD42024551000). Studies were extracted in duplicate, and data were meta-analyzed using generalized linear mixed-effects models. Risk of bias was appraised using a modified Joanna Briggs Institute checklist.

Results

We included 71 articles reporting serological or viral prevalence of OROV across nine countries. Between 2000–2024, pooled human seroprevalence among individuals with febrile illness or suspected of Oropouche infection was 12.6% [95% CI 5.3-26.9%] across four South American countries and seroprevalence of 1.1% [95% CI 0.5-2.3%] was observed in asymptomatic groups. Viral prevalence among individuals with febrile illness or suspected of Oropouche infection was 1.5% [0.8-3.0%] across seven South American countries and Haiti. Most studies used convenience sampling and RT-PCR or hemagglutination assays. In vector populations, positive OROV prevalence in Aedes aegypti and Culex quinquefasciatus was reported in two of 18 sources, while 10.0% and 7.5% animal host prevalence was reported in dogs and cattle, respectively. We found high risk of bias in 11.3% of studies in our critical appraisal, with most animal, human, and vector studies falling in the moderate risk of bias range.

Conclusions

Despite rising numbers of OROV reported cases, prevalence estimates remain limited by sparse surveillance and variable methodology. This review highlights the urgent need for standardized serological assays, community-based studies, and expanded surveillance in animal and vector reservoirs. A One Health approach is essential to monitor OROV transmission and inform regional preparedness efforts.

Source: 

Link: https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0013340

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#Pathobiology of Highly Pathogenic Avian #Influenza A #H5N1 Clade 2.3.4.4b Virus from #Pinnipeds on Tyuleniy Island in the Sea of #Okhotsk, #Russia

 

Abstract

Highly pathogenic avian influenza (HPAI) A(H5N1) clade 2.3.4.4b has recently emerged as a major threat to wildlife, agriculture, and public health due to its expanding host range and the increasing frequency of spillover into mammals. In July–August 2023, the mass death of over 3500 northern fur seals (Callorhinus ursinus) and at least one Steller sea lion (Eumetopias jubatus) was recorded on Tyuleniy Island in the Sea of Okhotsk, Russia. Two HPAI A(H5N1) viruses were isolated from fur seal carcasses and designated A/Northern_fur_seal/Russia_Tyuleniy/74/2023 and A/Northern_fur_seal/Russia_Tyuleniy/75/2023. Both viruses exhibited high pathogenicity in chickens (IVPI 2.7–3.0) and mice (MLD50 1.9–2.5 log10EID50/mL), with distinct differences in disease progression, histopathology, and organ tropism. Experimental infection of mice revealed that strain A/74/2023 induced more severe pulmonary and neurological lesions than A/75/2023. Whole-genome sequencing and phylogenetic analysis demonstrated close relatedness to HPAI H5N1 strains circulating in the Russian Far East and Japan from 2022 to 2023, with several mutations associated with mammalian adaptation, including NP-N319K and, in one isolate, PB2-E627K. According to our findings, northern fur seals (Callorhinus ursinus) on Tyuleniy Island acted as spillover hosts for the highly pathogenic avian influenza (HPAI) H5N1 virus of clade 2.3.4.4b. Furthermore, the high population density of fur seals and the extensive mortality observed during the outbreak highlight these animals’ potential role as another vessel for the evolution of avian influenza viruses. This study represents the first documented case of HPAI H5N1 in pinnipeds in the North Pacific region and supports previous reports indicating that pinnipeds, including northern fur seals, are highly susceptible to HPAI H5N1 clade 2.3.4.4b viruses.

Source: 

Link: https://www.mdpi.com/1999-4915/18/1/51

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#Coinfection of #SARS-CoV-2 and #Influenza: A Catastrophic Coexistence

 

Abstract 

SARS-CoV-2 is a major global public health burden associated with significant morbidity, mortality, and complications, including respiratory, cardiovascular, neurological, and digestive disorders. COVID-19 may induce venous and arterial thromboembolic complications, including deep vein thrombosis, myocardial infarction and cerebral infarction. Simultaneous myocardial and cerebral infarction, termed cardio-cerebral infarction, is exceedingly rare. There is only limited case of concurrent cardio-cerebral infarction in patients with COVID-19. Although there is no standard treatment for the condition, antiplatelet and anticoagulation agents should be used. We emphasize the catastrophic coexistence of concurrent cardio-cerebral infarction in a patient co-infected with SARS-CoV-2 and influenza A. We described a 75-year-old woman was admitted for SARS-CoV-2 and influenza A coinfection. She received anti-viral agent treatment for the virus infection. The patient presented with right side limbs weakness and declined consciousness. The magnetic resonance imaging of brain revealed acute cerebral infarction over the left corona radiata and basal ganglion. Meanwhile, acute myocardial infarction was diagnosed using electrocardiogram and elevated cardiac enzymes. Percutaneous coronary intervention and dual-antiplatelet agents were applied for the arterial thrombosis. The patient survived and recovered with mild residual hemiparesis. In addition, this is the first reported case of concurrent cardio-cerebral infarction in patients with SARS-CoV-2 and influenza A coinfection. Coinfection with SARS-CoV-2 and influenza A is associated with more complications including thromboembolic complications. Management of concurrent cardio-cerebral infarction poses challenges, as timely intervention is critical to prevent disability or death, yet aggressive anticoagulation risks hemorrhagic complications. Optimal treatment strategies remain unclear, highlighting the need for further research. This case underscores the importance of vigilance in managing thrombotic complications in patients with SARS-CoV-2 and influenza coinfection. Despite the downgrading of the COVID-19 pandemic, clinicians must remain alert to complex presentations caused by coinfections with respiratory viruses.

Source: 

Link: https://www.dovepress.com/coinfection-of-sars-cov-2-and-influenza-a-catastrophic-coexistence-peer-reviewed-fulltext-article-IDR

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Rapid #risk #assessment, acute event of potential public health concern: #Chikungunya virus disease, #Global (#WHO, Dec. 29 '25, summary)

 

Overall Risk statement

-- This RRA aims to assess the overall public health risk at the global level posed by the chikungunya virus (CHIKV) transmission during 2025, considering the criteria of potential risk for human health, the risk of geographical spread, and the risk of insufficient control capacities with available resources, and the implications for the 2026 transmission season. 

-- Chikungunya virus (CHIKV) poses a significant and growing global health risk due to large and widespread regional outbreaks in recent years, climate-driven mosquito expansion, lack of specific treatment, and increasing international travel. 

-- While mortality remains relatively low, the CHIKV infection can cause prolonged arthritis with disability as well as  severe illness in some patients. 

-- From 1 January to 10 December 2025, 502 264 CHIKV disease cases including  208 335 confirmed cases, and 186 CHIKV deaths, were reported globally. 

-- While certain WHO Regions are reporting lower case numbers compared to 2024, others are experiencing marked increases, furthermore some countries are seeing an emergence of chikungunya in previously unaffected populations. 

-- This heterogeneity in regional trends complicates the interpretation of the global situation. 

-- The data suggest localized resurgence or emergence in specific geographic areas. 

-- The region of the Americas has reported the highest number of confirmed cases followed by the European region (comprised of cases reported predominantly from French Overseas Departments in the Indian Ocean). 

-- Further, the potential for geographic spread remains substantial given that chikungunya can be introduced into new areas by infected travellers where local transmission may be established in the presence of competent Aedes mosquito, a susceptible population and favorable climatic and ecological conditions.  

-- The global public health risk posed by CHIKV transmission is assessed as moderate, driven by widespread outbreaks across multiple WHO regions during the 2025 season including areas with previously low or no transmission. 

-- The resurgence and emergence of cases in new geographic areas are facilitated by the presence of competent Aedes mosquito vectors, limited population immunity, favorable environmental conditions, and increased human mobility. 

-- The uneven distribution of cases complicates global interpretation, but highlights significant localized transmission. 

-- Control capacities remain challenged by gaps in surveillance, diagnostic access, healthcare infrastructure, and sustainable vector surveillance and control.  

-- Given the ongoing outbreaks reported globally in 2025, the potential for further spread in 2026 cannot be ruled out. 

(...)

Source: 

Link: https://www.who.int/publications/m/item/who-rapid-risk-assessment---chikungunya-virus--global-v.1

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Madonna at the Fountain, Jan van Eyck (1439)

 

Public domain.

Source: 

Link: https://www.wikiart.org/en/jan-van-eyck/madonna-at-the-fountain-1439

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A #Market-Based #Sentinel #Surveillance for an Early #Detection of Viral #Outbreaks

 

Abstract

Mexico has experienced recurrent viral epidemics of substantial intensity, including hyperendemic dengue, COVID-19, and recent reports of avian influenza A (H5N1) infections in birds, which pose an ongoing risk of zoonotic transmission. Mexico was also the location for the earliest detection of the pdmH1N1 virus during the 2009 influenza A pandemic. Under a One Health framework, markets represent a unique opportunity for low-cost virus monitoring at the human-animal interface. Under the hypothesis that these represent sentinel sites for an early virus detection, we implemented a pilot surveillance program at the central market of Merida city, Yucatan, Mexico, considered a regional hotspot for multiple and recent viral outbreaks. Longitudinal sampling was carried out over 11 months at 1-to-6-week intervals from April 2022 to February 2023. We used multi-type surveillance in mosquitoes, live poultry, and wastewater. All samples were screened using RT-qPCR. Positive samples for DENV, SARS-CoV-2 and avian influenza A were further sequenced and analysed under a phylogenetic and epidemiological approach. Through our entomological surveillance, we report the earliest detection of DENV-3 III-B3.2 (genotype III American II lineage, considered a major public health concern in Latin America) in Mexico, overlapping with the resurgence of DENV-3 as the predominant serotype driving the 2023 national epidemic, which showed an increased severity. Through wastewater surveillance, we consistently detect SARS-CoV-2 RNA in wastewater samples, coinciding with the two infection waves officially recorded at a city and state level. Finally, cloacal swabs taken from two juvenile birds at the market suggest that avian influenza A viruses circulated in live poultry sold at the market. These findings show that our market-based surveillance framework is effective for an early detection and monitoring of pathogenic viruses in urban settings, and could complement official epidemiological surveillance in low- and middle-income countries to strengthen early-outbreak warning systems.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

This study was supported by the John Fell OUP Research Grant ATD00390 (M.E.Z and M.U.G.K), the Wellcome Infectious Disease Award ?317324/Z/24/Z (M.G.K, H.P.G and M.E.Z), the Secretaria de Ciencia, Humanidades, Tecnología e Inovación award (SECIHTI, Mexico) through the PRONACES Health grant (PRONAII project number 303002, G.S) and the Ciencia Básica y de Frontera programme (CBF2023-2024-3184, M.G.K), and the UKRI Innovation BSRC/EPSRC/NIHR 971557 grant (A.R.S). M.G.K is funded through a Sanger International Fellowship award. M.E.Z is funded by a UCL Rosetrees Excellence Fellowship UCL2024\2. P.M.D was funded through the doctoral program at ‘Posgrado en Ciencias de la Produccion y de la Salud Animal-UNAM’ through the SECIHTI doctoral scholarship. M.U.G.K. acknowledges funding from The Rockefeller Foundation (PC-2022-POP-005), Health AI Programme from Google.org, the Oxford Martin School Programmes in Pandemic Genomics & Digital Pandemic Preparedness, European Union's Horizon Europe programme projects MOOD (#874850) and E4Warning (#101086640), Wellcome Trust grants 303666/Z/23/Z, 226052/Z/22/Z & 228186/Z/23/Z, the United Kingdom Research and Innovation (#APP8583), the Medical Research Foundation (MRF- RG-ICCH-2022-100069), UK International Development (301542-403), the Bill & Melinda Gates Foundation (INV-063472) and Novo Nordisk Foundation (NNF24OC0094346). B.G is further funded by Wellcome Trust grants 303666/Z/23/Z, 226052/Z/22/Z & 228186/Z/23/Z. The contents of this publication are the sole responsibility of the authors and do not necessarily reflect the views of the European Commission or the other funders. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Source: 

Link: https://www.medrxiv.org/content/10.64898/2025.12.22.25342882v1

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History of Mass Transportation: The Spoornet Class 14E Electric Locomotive

Von Col André Kritzinger, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=11506789

Source: 

Link: https://de.wikipedia.org/wiki/Spoornet-Klasse_14E

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History of Mass Transportation: The EC 250 ''Giruno'' Electric Multiple Unit Train

Par Daniel Wipf — Travail personnel, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=59022313

Source: 

Link: https://fr.wikipedia.org/wiki/EC_250_%C2%AB_Giruno_%C2%BB

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A #VSV #vector #vaccine simultaneously targeting #H5N1 HA & M2 induces robust neutralizing and ADCC #antibody responses & provides full protection vs lethal #H5N1 infection in mouse model

 

Abstract

Human (avian) influenza A viruses, especially highly pathogenic avian influenza (HPAI) viruses, pose a significant public health threat, and a multivalent vaccine is the primary prophylactic measure to control these viruses. To establish such a vaccine, we generated two multivalent vesicular stomatitis virus (VSV)-based vaccine candidates (V-EtM2e/H505 and V-EtM2e/H522) and characterized their ability to induce protective immune responses. Our results revealed that vaccine immunization in mice induced high humoral immune responses against both the HPAI hemagglutinin (HA) protein and the ectodomain of M2 (M2e) protein. Intriguingly, vaccine-immunized mouse sera exhibited highly efficient neutralizing activity against the corresponding H5 pseudovirus and mediated potent and broad antibody-dependent cellular cytotoxicity (ADCC) activity against M2e derived from human and avian influenza H5, H1, H3, and H7 viruses. Furthermore, both intranasal and intramuscular immunization provided efficient protection against HPAI H5N1 virus challenge in mice, with a 100% survival rate and a nondetectable viral load in several tissues. Notably, noninvasive mucosal (IN) delivery of V-EtM2e/H522 achieved protection equal to that of IM delivery at a 100-fold lower immunizing dose. These findings provide strong evidence for the effectiveness of a multivalent VSV-based vaccine against human (avian) influenza A viruses.

Competing Interest Statement

The authors have declared no competing interest.

Funder Information Declared

Canadian Institutes of Health Research, https://ror.org/01gavpb45, (OS1-190775)

Social Sciences and Humanities Research Council of Canada (SSHRC), (CBRF2-2023-00217)

Global Affairs Canada, https://ror.org/0427vvt16, Canadian International Development Scholarship (BCDI2030)

Source: 

Link: https://www.biorxiv.org/content/10.64898/2025.12.26.696590v1

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#Influenza #vaccination post - #COVID19 expands vaccine-specific effector #CD4 T-cells and Tregs under positive influence of host trained innate #immunity

 

Abstract

SARS-CoV-2 immunity and innate immune training may influence influenza vaccine immunogenicity. We investigated this in India. Adult volunteers with hybrid SARS-CoV-2 immunity were administered FluarixTM Tetra (GlaxoSmithKlein) 2022/2023 NH Vaccine in 2022. Significant induction of hemagglutinin inhibition-specific antibodies and polyfunctional central memory CD4+ T-cells (TCM) were observed 1-week post-vaccination with variable induction of CD8+T-cell and innate effectors. Vaccination also expanded Flu-specific regulatory T-cells (Treg), which negatively correlated with CD4 responses, highlighting vaccine immunogenicity may be subject to Treg dampening. FluarixTM did not boost SARS-CoV-2 immunity. However, SARS-CoV-2-specific T-cell responses correlated positively with vaccine-induced T-cell responses. We evaluated trained immunity post-COVID-19 as a potential regulatory mechanism linking SARS-CoV-2 and heterologous vaccine immunogenicity. We observed, elevated frequencies of basal bacterial Lipopolysaccharide (LPS)-induced IL-6+IL1β+HLA-DR+CD14+CD16- frequencies post-COVID-19 correlated positively with vaccine-induced Fluarix-specific CD4 T-cell frequencies. Our study highlights a potential positive role for COVID-19-driven immune imprinting on heterologous vaccine immunogenicity in a post-COVID-19 era.

Source: 

Link: https://www.nature.com/articles/s41541-025-01331-6

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Genotype A3 #influenza #H5N1 isolated from fur #seals shows high virulence in #mammals, but not #airborne transmission

 

Abstract

The global spread of highly pathogenic avian influenza A(H5N1) clade 2.3.4.4b viruses has recently extended to include diverse mammalian species, raising new concerns about pandemic risk. In 2023, this clade was first detected in Russian marine mammals during a mass mortality event among northern fur seals in the Far East. Genetic analyses revealed the causative viruses to belong to genotype A3 of European origin, which is known to have circulated in wild birds across the Far East since 2022. Notably, these isolates harbor the mammalian-adaptive substitutions PB2-K482R and NP-N319K—mutations previously linked to enhanced virulence in non-H5 avian influenza viruses, but whose impact on A(H5N1) clade 2.3.4.4b viruses remained to be characterized. The heightened virulence of A3 genotype viruses is confirmed by data obtained via a mouse model. However, despite these adaptive changes, ferret transmission models showed no evidence of airborne transmission of the fur seal-derived virus. Our findings indicate that while PB2-K482R and NP-N319K may contribute to increased mammalian pathogenicity, they do not significantly increase the efficiency of respiratory transmission—a key prerequisite for human pandemic potential. Although suggesting a limited immediate pandemic threat from this A3 genotype, these results underscore the critical need for continued surveillance and functional assessment of emerging mammalian-adaptive mutations in circulating A(H5N1) viruses.

Source: 

Link: https://www.nature.com/articles/s41598-025-28032-3

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#Macrolide #Resistance and P1 Cytadhesin Genotyping of #Mycoplasma pneumoniae during #Outbreak, #Canada, 2024–2025

 

Abstract

We investigated macrolide resistance and P1 genotypes of Mycoplasma pneumoniae during the 2024–2025 outbreak in Hamilton, Ontario, Canada. Macrolide resistance remained stable at ≈10%–20%, but significant shifts in P1 genotype distribution and resistance rates in P1 types occurred, indicating notable changes in M. pneumoniae molecular epidemiology in Ontario since 2011–2012.

Source: 

Link: https://wwwnc.cdc.gov/eid/article/31/12/25-0872_article

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#Effectiveness of the 2024–2025 #KP2 #COVID19 #vaccines in #USA during long-term follow-up

 

Abstract

Up-to-date estimates of COVID-19 vaccine effectiveness (VE) are needed to inform COVID-19 vaccination strategies and recommendations. This target trial emulation study aimed to estimate the long-term vaccine effectiveness (VE) of the 2024-2025 COVID-19 vaccines targeting the KP.2 Omicron variant within the Veterans Health Administration. The study population (90.9% male, mean age 70.7 years) included 538,631 pairs of vaccinated (i.e., received the KP.2 COVID-19 vaccine) and matched unvaccinated (i.e., did not receive the KP.2 COVID-19 vaccine) persons enrolled from August 2024 to January 2025. Over a mean follow-up of 172 days (range 97-232) extending to April 12, 2025, VE was low against laboratory-diagnosed SARS-CoV-2 infection (16.60%, 95% confidence interval [CI], 11.92-21.44), SARS-CoV-2-associated emergency department/urgent care (ED/UC) visit (21.05%, 95% CI, 14.22-27.21), SARS-CoV-2-associated hospitalization (19.53%, 95% CI 6.56-30.10) and much higher against SARS-CoV-2-associated death (65.53%, 95% CI 27.79-83.37). VE declined from 60 to 90 to 120 days against infection (31.28%, 25.81%, 22.44% respectively), ED/UC visit (34.40%, 29.19%, 25.71% respectively), hospitalization (37.39%, 28.98%, 22.52% respectively) and death (75.02%, 71.02%, 63.08% respectively). In conclusion, COVID-19 vaccines targeting the KP.2 variant used in the 2024-2025 season offered high protection against death and modest protection against infection, ED/UC visits or hospitalization, and VE declined over time.

Source: 

Link: https://www.nature.com/articles/s41467-025-67796-0

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