Cross-reactive T-cell responses against #BDBV in #humans after rVSVΔG-ZEBOV-GP #vaccination

 

{Excerpts}

(...)

Our study shows that a single immunisation with the available, licensed EBOV vaccine induces T-cell cross-reactivity against BDBV and to a lesser extent against SUDV. Although it is not known whether these T cells contribute to improved clinical outcomes upon BDBV exposure in humans, preclinical studies show that T-cell responses are required for vaccine-mediated protection in non-human primates: CD4 T cell help to B cells is required for protection against disease caused by EBOV,10 and depletion studies have also shown a protective role of CD8 T cells.11

Our study has limitations. Due to the small sample size and single measured timepoint, dose–response differences and long-term persistence of the cross-reactive T-cell response could not be assessed. This study was performed in healthy adults in Germany, thus representativeness of populations in areas affected by the BDBV outbreak is limited.

Although a correlate of protection against disease caused by BDBV has not been defined, our findings provide first evidence that rVSVΔG-ZEBOV-GP vaccination against EBOV induces BDBV-cross-reactive T-cell responses. In the absence of a BDBV-specific vaccine, these data support the systematic evaluation of the available EBOV vaccine within clinical trials during the current outbreak.

Source: 

Link: https://doi.org/10.1016/S1473-3099(26)00529-3

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Strong #Protein #Responses to Acute #Infection Control General Post-Viral #Sequelae and #SARS-CoV-2-specific #Neurocognitive Sequelae

 

Abstract

After serious infections, many survivors fully recover while others face persistent symptoms including neurocognitive dysfunction, cardiopulmonary instabilities and disabling fatigue, classified broadly as Post-Acute Infection Syndromes (PAIS). Post-Acute Sequelae of COVID19 (PASC) is one special case. To test whether acute infection initiates PAIS, we analyzed proteins in 173 saliva samples collected during severe respiratory viral infections and tracked patient outcomes for five years. We discovered 44 proteins, all derived from interferon stimulated genes, that respond strongly to acute infection. Rates of post-acute syndromes were similar regardless of infection, but the types of Sequelae differed by virus. High expression of 19 proteins predict low General Sequelae rates across all viruses. High expression of 23 overlapping proteins predict low Neurocognitive Sequelae rates only with SARS-CoV-2 infections. We propose that low expressions of these proteins, which control viral replication, innate immunity, and secondary autoimmunity, combine to precipitate PAIS and PASC.

Competing Interest Statement

Theodore G. Liou, Judy L Jensen and Kristyn A Packer received research funding from Anagram, Aridis, BioMX, Calithera, Clarametyx, Judy L Jensen and Kristyn A Packer received research funding from Anagram, Aridis, BioMX, Calithera, Clarametyx, Gilead, Insmed, Laurent, Novartis, Sionna, SpliSense, the US Cystic Fibrosis Foundation's Therapeutic Development Network and Vertex for performance of clinical studies during the study and manuscript preparation period. Theodore Liou is a member and Rhonda Szczesniak is vice-chair of the Cystic Fibrosis Foundation Clinical Research Committee. Theodore Liou and Frederick Adler, through the University of Utah, are named as inventors on the following patent applications related to the proteins identified in this manuscript: (1) a provisional patent application titled "DIAGNOSTICS AND TREATMENTS FOR ACUTE AND POST-VIRAL DISEASE BASED ON INNATE IMMUNE RESPONSES TO SARS-COV-2 INFECTION," serial number 63/792,687, filed 4/22/2025; (2) a provisional patent application titled "ADDITIONAL INNATE IMMUNE RESPONSES WITH DIAGNOSTIC AND TREATMENT POTENTIAL FOR POST-ACUTE SEQUELAE OF COVID19 SYNDROME AND FOR POST-ACUTE INFECTION SYNDROME," serial number 63/979,883, filed 2/10/2026; (3) a Patent Cooperation Treaty (PCT) application titled "METHODS FOR PREDICTING POST-ACUTE SEQUELAE OF VIRAL INFECTIONS USING INTERFERON STIMULATED GENE PROTEINS," serial number PCT/US2026/024520, filed 4/21/2026, which incorporates subject matter from (1) and (2); and (4) a provisional patent application titled "ADDITIONAL ACUTELY EXPRESSED PROTEINS PROTECTIVE AGAINST NEUROCOGNITIVE AND GENERAL POST-VIRAL SEQUELAE," serial number 64/102,461, filed 6/30/42026. The applicant on all applications is the University of Utah.

Source: 

Link: https://www.medrxiv.org/content/10.64898/2026.08.27.26361488v2

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Serologic #Testing for #MERS #Coronavirus and #SARS-CoV-2 Cross-Reactive Immune Responses, the #Netherlands

 

Abstract

Cross-reactive SARS-CoV-2–specific antibodies could compromise the specificity of MERS-CoV serology, potentially leading to misclassification of infection history. SARS-CoV-2 exposure induced MERS-CoV antibodies primarily targeting the conserved S2 domain, with occasional neutralizing capacity. Combining MERS-CoV S1 binding with neutralization, however, limited the influence of SARS-CoV-2–induced cross-reactivity on MERS-CoV serology.

Source: 

Link: https://doi.org/10.3201/eid3211.260690

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#Global Genomic #Surveillance of #MERS #Coronavirus

 

Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV) is a persistent zoonotic and epidemic threat. We analyzed 807 publicly available human- and camel-derived MERS-CoV genomes collected during 2012–2024 to assess global genomic surveillance. Most sequences originated from Saudi Arabia and the United Arab Emirates. Major gaps in surveillance persist across Africa and South and Central Asia despite large camel populations, active trade, and evidence of viral circulation. Phylogenetic analysis confirmed predominance of clade B in the Arabian Peninsula and clade C in East Africa, consistent with regional patterns. We identified uneven sampling, incomplete metadata, and long delays between sample collection and public sequence submission, often spanning years. Those limitations reduce the value of genomic data for timely situational awareness. Integrating genomic with population and trade data supports timelier, more representative, and coordinated One Health surveillance for MERS-CoV but reveals major blind spots.

Source: 

Link: https://doi.org/10.3201/eid3211.260668

____

#Evidence of Exposure to Highly Pathogenic Avian #Influenza #H5 Viruses in East #Greenland Polar #Bears

 

Abstract

We detected influenza A virus antibodies in plasma collected from East Greenland polar bears during subsistence hunts in 2024 (3/14 [21%]) and 2025 (6/14 [43%]). Four bears from 2025 had antibodies for the globally emerging highly pathogenic avian influenza virus H5 clade 2.3.4.4b, consistent with survival after exposure.

Source: 

Link: https://doi.org/10.3201/eid3211.261050

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Subacute Sclerosing #Panencephalitis after #Measles #Outbreaks, the #Philippines, 2007–2022

 

Abstract

Subacute sclerosing panencephalitis (SSPE) is a delayed, almost uniformly fatal complication of measles. The Philippines had measles outbreaks in 2010–2011, 2013, and 2018–2019; the last was the largest in the World Health Organization Western Pacific Region. Published SSPE data from the Philippines end in 2015. We reviewed all 20 children admitted with SSPE to a tertiary pediatric hospital in Quezon City during 2007–2022 and estimated year of measles infection. Median patient age was 6.2 years at hospital admission and 0.7 years at reported measles illness. Five (25.0%) of 20 admissions occurred in 2022, and estimated infection dates placed 4 patients within the 2018–2019 outbreak; all were admitted during 2020–2022. Given the multiyear latency of SSPE, additional cases might emerge over coming years. Reported measles history could not be established in one quarter of patients. Strengthened measles surveillance and sustained 2-dose vaccination coverage are needed.

Source: 

Link: https://doi.org/10.3201/eid3211.261395

____

Efficacy, safety, and immunogenicity of a 9-valent vaccine (ExPEC9V) for #prevention of invasive #Escherichia coli disease in older #adults: a phase 3, randomised, placebo-controlled trial (E.mbrace)

 

Summary

Background

Invasive Escherichia coli disease (IED) caused by extraintestinal pathogenic Escherichia coli (ExPEC) can lead to bacteraemia and sepsis. ExPEC9V is a conjugate vaccine targeting nine E coli O-serotypes that account for most E coli bloodstream infections. We aimed to evaluate ExPEC9V for safety, immunogenicity, and prevention of IED caused by ExPEC9V O-serotypes in adults aged 60 years and older.

Methods

In this randomised, double-blind, placebo-controlled, phase 3 study conducted at 332 clinical sites in 20 countries (E.mbrace), we enrolled participants aged 60 years and older in stable health and with a history of urinary tract infection (UTI) within the previous 2 years. Participants were randomly assigned (in blocks of no set size with the use of interactive web response system, stratified by age and presence or absence of risk factors for complicated UTI) 1:1 to receive a single dose of intramuscular ExPEC9V or placebo. Participants, study-site personnel, and investigators remained masked to group allocation throughout the study. The primary endpoint was first IED in blood or sterile sites caused by ExPEC9V O-serotypes in the per-protocol efficacy analysis set (all randomly assigned, vaccinated participants without major protocol deviations); secondary endpoints included immunogenicity assessment in a subset of participants. Safety endpoints included solicited (safety subset), unsolicited (full analysis set), and serious (full analysis set) adverse events. A prespecified futility analysis conducted when at least 40% of the expected 53 IED events had occurred indicated lack of efficacy, leading to early study termination. We present final study results (data up to the date of the futility announcement), when 17 701 of the planned 19 800 participants had been vaccinated. This trial is registered with ClinicalTrials.gov (NCT04899336).

Findings

Participants were enrolled between June 30, 2021, and Feb 13, 2025. Of 18 844 individuals assessed for eligibility, 17 701 were enrolled, randomly assigned, and vaccinated (8858 with ExPEC9V and 8843 with placebo). The per-protocol efficacy included 17 637 participants (8822 for ExPEC9V and 8815 for placebo). There were 24 IED cases (11 in vaccine and 13 in placebo groups) caused by ExPEC9V O-serotypes in blood or sterile sites, yielding a vaccine efficacy of 14·63% (95% CI −106·57 to 65·38), indicating no protective effect. ExPEC9V had an acceptable safety profile, with more frequent low-grade adverse events in the ExPEC9V versus placebo group, balanced serious adverse event distribution among both groups, and no vaccine-related deaths.

Interpretation

In this large phase 3 trial of older adults, ExPEC9V did not demonstrate efficacy in preventing first IED caused by ExPEC9V O-serotypes, despite generating robust and sustained antibody responses. Development of the ExPEC9V vaccine has been discontinued.

Funding

Johnson & Johnson and Sanofi.

Source: 

Link: https://doi.org/10.1016/S1473-3099(26)00469-X

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#Human #Infection with Avian #Influenza #H7N7 Virus, #Taiwan, 2026

 

Abstract

Low pathogenic avian influenza A(H7N7) virus detected in a poultry worker in Taiwan, 2026 was related to viruses circulating in Asian wild birds and possessed PB2 E627K, a mammalian adaptation marker. Enhanced surveillance for H7 viruses in poultry and rapid characterization of human cases are essential to assess pandemic potential.

Competing Interest Statement

The authors have declared no competing interest.

Source: 

Link: https://doi.org/10.64898/2026.10.09.26365013

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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

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#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

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#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

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#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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