The transition to #postpartum #lactation establishes a state of maternal #antiviral #resilience

 

Abstract

Influenza A virus (IAV) causes severe disease during late pregnancy, yet how maternal adaptations in host defense shape susceptibility following childbirth remains unknown. Here, we show that the postpartum period represents a state of enhanced maternal antiviral immunity. Across postpartum stages, dams infected before weaning exhibited increased survival and reduced disease following lethal IAV challenge compared with nonpregnant females. Postpartum protection was associated with enhanced viral clearance and increased pulmonary antigen-specific CD8+ T cells and IL-17A-producing gamma-delta T cells. We identify the transition into lactation as a critical determinant of this protection. Protection extended to highly pathogenic avian influenza. Together, these findings reveal that maternal antiviral immunity remains actively shaped after childbirth, establishing the postpartum lactational period as a distinct state of maternal antiviral resilience.

Competing Interest Statement

KK and PS are co-inventors on a patent relating to this work. KK and PS are co-founders of Coralie Bio, Inc. that may benefit financially from the work described in this article.

Funder Information Declared

National Institutes of Health, https://ror.org/01cwqze88, 1R01HD120540, 1F31AI191458

David and Lucile Packard Foundation, https://ror.org/032atxq54, Packard Fellowships for Science and Engineering

U.S. National Science Foundation, https://ror.org/021nxhr62, Graduate Research Fellowship Program

Howard Hughes Medical Institute, https://ror.org/006w34k90, Gilliam Fellowship Program

Blavatnik Family Foundation, Blavatnik Biomedical Accelerator at Harvard University

Wyss Institute for Biologically Inspired Engineering

Source: 

Link: https://doi.org/10.64898/2026.10.02.756285

____

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#Antiviral Susceptibility of Clade 2.3.4.4b #H5N1 and #H5N5 #Influenza Viruses Detected in #Birds in #Russia During 2021–2022

 

Abstract

In this study, we aimed to analyze the antiviral susceptibility of clade 2.3.4.4b H5N1 and H5N5 influenza viruses detected in Russia during 2021–2022. During this period, we investigated 40 avian influenza outbreaks in wild and domestic birds, isolating 109 H5N1 and 9 H5N5 strains. Using a genetic approach, we analyzed the presence of markers associated with reduced susceptibility to baloxavir and M2 blockers, as well as markers of reduced inhibition by neuraminidase inhibitors (NAIs). Additionally, the isolated strains were tested in a functional assay to evaluate the inhibitory activity of oseltamivir, zanamivir, and peramivir against viral neuraminidase. None of the isolates harbored genetic markers of reduced susceptibility to M2 blockers and baloxavir or reduced inhibition by NAIs. Functional assay showed that the median IC50 values of oseltamivir, zanamivir, and peramivir were 1.73, 0.49, and 0.16 nM for the H5N1 subtype, and 0.65, 1.13, and 0.12 nM for the H5N5 subtype, respectively. None of the tested strains demonstrated a ≥10-fold increase in NAI IC50 values compared to the corresponding subtype medians, and were thus classified as having a normal level of inhibition. The median IC50 values of the NAIs determined for the tested avian viruses were comparable to those of a susceptible seasonal A(H1N1)pdm09 strain, except for a slight reduction in oseltamivir activity against H5N1 viruses (4.3-fold) and zanamivir activity against H5N5 viruses (3.4-fold). Our study revealed a group of H5N1 viruses whose NA belonged to the ea5.1 genetic subclade, characterized by NA-Y253H and T452I amino acid substitutions, which exhibited a 28.8-fold decrease in oseltamivir IC50 values compared to the subtype median. These strains were detected in the European and Ural regions of Russia between May 2022 and January 2023, with no subsequent detections in the available surveillance data. To the best of our knowledge, such strains have not been identified outside Russia.

Source: 

Link: https://doi.org/10.3390/v18101126

____

#Filovirus reactive #antibodies in #wildlife hunting #communities suggest ongoing zoonotic #spillover in forested #Guinea

 

Abstract

Forested Guinea has been the site of multiple high-consequence viral spillover events, including the index case of the 2013-16 West African Ebola epidemic. Deforestation and wildlife hunting rapidly expand the human-animal interface, increasing opportunities for transmission. Here we integrate serologic, spatial and questionnaire data to characterize zoonotic filovirus spillover events and risk factors amongst wildlife hunter communities in Forested Guinea. Hunters and close contacts from 43 villages in 2017 (n = 511) and 2023 (n = 648) were screened using a multiplex microsphere-based immunoassay panel of 9 filoviruses, identifying IgG binding against Ebola virus (EBOV) in 57/1159 individuals (4.9%), as well as species-specific binding against Bundibugyo (BDBV) (49/1159, 4.2%), Taï Forest (TAFV) (13/1159, 1.1%), Reston (4/1159, 0.3%), Měnglà (MLAV) (8/1159, 0.7%), Lloviu (LLOV) (8/1159, 0.7%) and Bombali (BOMV) (1/1159, 0.1%) viruses. Parallel pseudotyped virus neutralization assays identified species-specific neutralization of EBOV, BDBV and TAFV, as well as likely cross-neutralization of BOMV, LLOV and MLAV, suggesting multiple zoonotic virus spillover events. Mixed-effects regression analyses of satellite-derived land-cover data identified environmental risk factors (including forest fragmentation) reflecting potential pathways of exposure. Together, our data suggest multiple ongoing zoonotic filovirus spillover events in wildlife hunting communities and highlight the importance of landscape configuration in driving pathogen spillover.

Source: 

Link: https://doi.org/10.1038/s41467-026-77653-3

____

#Serological and transcriptomic response of African fruit #bats to immune challenge with recombinant #vaccines expressing #Ebola or #Nipah virus #antigens

 

Abstract

Bats are hosts to diverse zoonotic viruses which can cause high case fatality rates in humans. Since detecting viruses in bats is difficult, antibodies are often used for surveillance, though their significance remains unclear in the absence of in vivo immunological studies. To address this knowledge gap, we measured antibody production and gene expression in bats following injection with vaccines encoding either a Nipah virus G glycoprotein or an Ebola virus GP glycoprotein. We selected two African bat species with overlapping ranges, Eidolon helvum (confirmed reservoir of henipaviruses) and Epomophorus gambianus (putative reservoir of filoviruses). Using a Luminex-based multiplex microsphere immunoassay and a pseudotype virus neutralization assay, we observed an increase in antibodies against the Nipah glycoprotein in most bats that received the Nipah vaccine. In contrast, we could only detect anti-Ebola glycoprotein antibodies in one bat species, Ep. gambianus, in response to the Ebola vaccine. Transcriptomic analysis in Ei. helvum revealed that genes involved in ISGylation and T-cell differentiation pathways were differentially expressed in response to the Ebola, but not the Nipah, vaccine. These results demonstrate species-specific differences in responses to antigen exposure, offering insights into bat adaptive immune systems and providing calibration for serological data from wild bats.

Source: 

Link: https://doi.org/10.1098/rsos.252189

____

Integrated in vivo and transcriptomic analyses of lethal #Oropouche virus #infection reveal suppression of pathogenic host responses by #antiviral therapy

 

Abstract

Oropouche virus (OROV) is an emerging arbovirus responsible for large outbreaks of febrile illness in Central and South America, with increasing reports of severe neurological disease and fatal outcomes. Despite its growing public health impact, no approved antiviral therapies or vaccines are currently available. Here, we show that favipiravir, a broad-spectrum nucleoside analogue, robustly suppresses OROV replication and disease in vivo. In a lethal Syrian hamster model, favipiravir treatment provided complete protection against OROV infection, preventing viral dissemination to peripheral organs and the central nervous system, and remained highly effective when administration was initiated after infection. In contrast, insufficient antiviral control resulted in viral neuroinvasion and fatality. To define host responses associated with OROV pathogenesis and their modulation by antiviral therapy, we performed transcriptomic profiling of liver and brain tissues. OROV infection induced interferon-driven inflammatory programs accompanied by marked disruption of metabolic and tissue homeostatic pathways, whereas these transcriptional signatures were largely abrogated by favipiravir treatment. Together, our findings identify favipiravir as a potent antiviral candidate against OROV and provide the first in vivo, tissue-resolved transcriptomic framework of OROV infection, linking effective viral suppression with the prevention of neuroinvasion and pathogenic host responses. These results highlight antiviral intervention as a viable strategy to mitigate OROV-associated disease and mortality.

Source: 

Link: https://doi.org/10.1371/journal.ppat.1014647

____

The #mammalian-adaptive #PB2-E627K substitution preserves viral fitness of clade 2.3.4.4b #H5N1 HPAIV in #birds

 

Abstract

Since emerging in 2020, clade 2.3.4.4b H5N1 high pathogenicity avian influenza virus (HPAIV) has disseminated globally, causing substantial infection and mortality in wild birds and poultry. Additionally, numerous spill-over events into mammals have occurred, including mass mortalities and sporadic human infections. Such events can drive the acquisition of mammalian-adaptive mutations, which further increase the risk to humans; the most well characterised mutation is the glutamate to lysine change at amino acid position 627 in the polymerase basic 2 protein (PB2-627K). Across avian influenza viruses, PB2-627K enhances polymerase activity and replication in mammalian cells, increasing zoonotic and pandemic potential. However, bioinformatic analyses indicate that PB2-627K remains rare among clade 2.3.4.4b H5N1 viruses circulating in avian populations. Here, we investigated the impact of PB2-627K on viral fitness in avian hosts to assess the potential for mammalian-adapted viruses to re-establish in birds, mimicking infection of avian species following scavenging on mammalian species where PB2-627K has already emerged. Using a representative H5N1 virus (European genotype AB), PB2-627K increased polymerase activity and replication in human cells without compromising replication in avian cells. A mammalian-derived PB2-627K H5N1 isolate from a fox exhibited comparable replication kinetics and transmission efficiency in chickens and ducks to a closely related PB2-627E virus. Notably, PB2-627K remained genetically stable at consensus level following infection and transmission in both avian hosts. These findings demonstrate that mammalian-adaptive mutations acquired during spill-over can be maintained in avian populations, potentially elevating zoonotic risk and underscoring the importance of surveillance for such mutations in birds.

Source: 

Link: https://doi.org/10.64898/2026.10.06.757006

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Persistent #influenza A #RNA detection in a #fatal #pediatric case of influenza-associated #encephalopathy

 

Abstract

Influenza-associated encephalopathy (IAE) is a life-threatening complication of influenza. We report a case of a 9-year-old boy diagnosed with fulminant IAE. The patient received life-sustaining support, intensive immunomodulatory therapy, and antiviral therapy. Following an initial single dose of baloxavir marboxil, persistent influenza A (H3N2) RNA detection prompted a multi-targeted antiviral regimen (oseltamivir, baloxavir marboxil, peramivir, and onradivir) as salvage therapy. Nevertheless, influenza A RNA remained detectable for more than 1 month, potentially reflecting severe neurological injury, immunosuppression, and impaired airway clearance.

Source: 

Link: https://doi.org/10.1016/j.jiph.2026.103380

____

#Urban #waterfowl harbour geographically connected #viral communities across #Aotearoa New Zealand

 

Abstract

Urban waterfowl are important natural reservoirs of viruses that can affect wildlife, livestock and human health, yet the diversity and spatial distribution of these viral communities remain poorly understood. Here, we characterised the faecal viromes of urban waterfowl sampled from 13 locations across the length of Aotearoa (New Zealand). We identified 96 avian viruses (50 species) spanning nine viral families, including 33 previously undescribed viruses. Picornaviruses were the most widespread viral group, while several viruses were closely related to those previously identified in Australian waterfowl, indicating that some viral lineages are likely distributed across the broader Australasian region. Despite sampling locations spanning more than 1,500 km, virome composition exhibited little evidence of geographic structure, with little difference in viral diversity or community composition between sampling locations. Network analyses similarly demonstrated extensive sharing of virus species among sampling locations, indicating little geographic structuring of virome composition among urban waterfowl. In addition, we recovered the complete genome of a low-pathogenic A(H3N8) influenza A virus from mallards (Anas platyrhynchos) in the most southern region of Aotearoa. These findings reveal extensive viral diversity and widespread connectivity among urban waterfowl, providing new insights into viral ecology and the potential for widespread virus distribution across Aotearoa.

Competing Interest Statement

The authors have declared no competing interest.

Funder Information Declared

Te Niwha, Aotearoa's Infectious Disease Research Platform, TN/SWC/24/UoOJG

New Zealand Royal Society Rutherford Discovery Fellowship, RDF-20-UOO-007, MTP-UOO2504

Source: 

Link: https://doi.org/10.64898/2026.10.04.756485

____

#Teratogenic Effects and Outcomes of #Congenital #Oropouche Virus Infection: Current Evidence, Pathophysiological Mechanisms, and Research Priorities

 

Abstract

Background: 

Oropouche virus (OROV), an Orthobunyavirus endemic to Latin America, has recently emerged as a pathogen of concern in pregnancy following reports of vertical transmission, fetal demise, congenital anomalies, and neonatal disease. The unprecedented 2023–2025 outbreaks in Latin America have expanded the geographic distribution of OROV and renewed concerns regarding its potential as an emerging human teratogen. 

Methods: 

We conducted a narrative comprehensive review of the literature focusing on epidemiology, maternal–fetal transmission, placental infection, experimental models, fetal and neonatal outcomes, and comparisons with other congenital arboviral infections. 

Results: 

Increasing evidence supports the ability of OROV to infect the placenta, cross the maternal–fetal interface, and invade fetal tissues. Human cases have documented miscarriage, stillbirth, fetal demise, microcephaly, ventriculomegaly, cerebral atrophy, corpus callosum abnormalities, posterior fossa defects, arthrogryposis, and neonatal death following maternal infection. Viral RNA and OROV-specific antibodies have been detected in placental, fetal, and neonatal samples, providing direct evidence of congenital infection. Experimental studies using trophoblast cultures, placental organoids, neural progenitor cells, brain organoids, and animal models have confirmed placental susceptibility, vertical transmission, fetal neurotropism, and disruption of neurodevelopment. The congenital phenotype shares important similarities with congenital Zika syndrome and other neurotropic arboviral infections. 

Conclusions: 

OROV is newly and increasingly recognized as a vertically transmissible neurotropic arbovirus with potential teratogenic effects. Although biological plausibility is supported by converging clinical and experimental findings, prospective epidemiological studies are urgently needed to quantify risks, identify determinants of fetal injury, and define long-term outcomes among affected children.

Source: 

Link: https://doi.org/10.3390/v18101101

____

#Antibodies targeting a conserved cryptic epitope at the #influenza hemagglutinin head-stem interface via distinct binding modes

 

Abstract

Influenza A virus continues to pose pandemic threats, as demonstrated by the recent global spread of highly pathogenic H5N1 strains. Consequently, the development and characterization of vaccines targeting zoonotic influenza subtypes have become a major focus of the field. In this study, we characterize two broadly reactive antibodies previously isolated from H5N1 vaccinees. Although they have distinct immunoglobulin germline gene usage and binding modes, cryo-EM analysis shows that both antibodies share a highly conserved cryptic epitope at the interface of the hemagglutinin (HA) head and stem domains. The antigenicity of this epitope is influenced by natural amino acid variation at residue 293 of HA subunit 1, and its access is facilitated by acid-induced conformational change of HA. Nevertheless, both antibodies are non-neutralizing and possess only marginal protective efficacy against seasonal and H5N1 viruses in vivo, thus representing suboptimal vaccine responses. Overall, our findings expand the interactions of cross-reactive antibodies with an under-characterized HA epitope and provide insights for next-generation influenza vaccine design.

Competing Interest Statement

N.C.W. consults for HeliXon. All authors declare no other competing interests.

Funder Information Declared

Research Grants Council of the Hong Kong Special Administrative Region, China, HKU C7053-24G

Health and Medical Research Fund, no. 24230352

NIH/NIGMS, GM158411

Vallee Scholars Program

Source: 

Link: https://doi.org/10.64898/2026.09.24.754278

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Establishment of an avian #influenza #surveillance program in #Australia's largest #river basin

 

Abstract

To-date Australia has had mostly coastal occurrences in a small but growing number of species of high pathogenicity avian influenza (HPAI) H5N1 clade 2.3.4.4b. The potential impacts of expected spread are the focus of significant preparation activities. Here we report on early surveillance undertaken in 2025-26 in the Murray-Darling Basin, Australia's largest river system, which contains internationally important wetlands that support large multi-species aggregations of waterbirds vulnerable to mass mortality. We detected two low pathogenicity avian influenza (LPAI) viruses of Australian origin in wild waterbirds. Ongoing surveillance will aid in early detection and rapid response in the case of a major inland outbreak of H5N1.

Competing Interest Statement

The authors have declared no competing interest.

Funder Information Declared

Department of Climate Change, Energy, the Environment and Water

Source: 

Link: https://doi.org/10.64898/2026.09.09.750291

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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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