ETIDIOH - NEW

  Abstract Influenza remains a significant global public health concern. Live-attenuated influenza vaccines (LAIVs) are recognized as effective interventions for influenza prevention. Currently, two types of LAIVs are licensed for human use: one developed through cold-adapted viral gene mutation and the other through the deletion of the viral NS1 gene . However, the similarities and differences in these two LAIVs’ efficacy, safety, and immune responses have not been thoroughly studied. This study constructed a gene-deficient live-attenuated vaccine strain, CA4-dNS1, and a gene locus-mutated attenuated vaccine strain, CA4-cold , to compare their in vivo and in vitro replication capacity , broad-spectrum protective efficacy , safety, and immunogenicity . The results showed that both LAIVs provide comparable broad-spectrum protection against lethal H1N1 and H5N1 influenza challenges in mice and induce similar humoral and mucosal immune responses . Notably, the CA4-cold vaccine strain ...

  Abstract Avian influenza viruses (AIVs) pose a significant zoonotic threat, with the emerging H3N8 subtype raising increasing concern due to sporadic human infections . Current strategies for risk assessment of novel AIVs primarily rely on genetic surveillance and isolated case reports, which provide limited insight into their cross-species transmission potential . However, these approaches may overlook critical phenotypic determinants , such as pathogenicity, transmissibility, and environmental persistence , that directly influence zoonotic risk . This study investigates the evolutionary relationships , receptor-binding properties, replication dynamics, pathogenicity in mice, transmission efficiency in guinea pigs, and environmental persistence of three H3N8 strains isolated from a live poultry market . All three H3N8 strains bound exclusively to α-2,3 sialic acid receptor and achieved 100% transmissibility among guinea pigs through direct contact . Notably, the environment-orig...

  Abstract Finland faced an outbreak of highly pathogenic clade 2.3.4.4b A(H5N1) avian influenza in 2023, which spread from wild birds to fur farms . Vaccinations of at-risk individuals began in June 2024 using the MF59-adjuvanted inactivated A(H5N8) vaccine (Seqirus; A/Astrakhan/3212/2020, clade 2.3.4.4b). Here, in an observational study , we assessed vaccine-induced immune responses in occupational at-risk individuals participating in the phase IV trial , including virus-specific antibody (n = 39 individuals) and T-cell (n = 18 individuals) responses. Vaccination elicited functional antibodies against the vaccine virus and two heterologous clade 2.3.4.4b strains associated with outbreaks on Finnish fur farms and dairy cattle in the United States . Among previously unvaccinated individuals, seroprotection rates against the vaccine virus were 83% (95% CI 70–97%) by microneutralization assay (titre ≥20) and 97% (90–100%) by haemagglutination inhibition assay (titre ≥40). In those pr...

  Am J Respir Crit Care Med SARMA A, Christenson SA, Shoshana BZ, Oliveira AP, et al Acute Respiratory Distress Syndrome Molecular Phenotypes Have Distinct Lower Respiratory Tract Transcriptomes. Am J Respir Crit Care Med. 2025;211:2352-2362. PubMed           Abstract available Ann Intern Med SOUMARE A, Kapfer T, Botrel T, Adda L, et al Systemic Corticosteroids, Mortality, and Infections in Pneumonia and Acute Respiratory Distress Syndrome : A Systematic Review and Meta-analysis. Ann Intern Med. 2025 Dec 2. doi: 10.7326/ANNALS-25-03055. PubMed           Abstract available BMJ LOGAN M FDA claims 10 child deaths caused by covid-19 vaccine, vows to tighten vaccine approvals. BMJ. 2025;391:r2546. PubMed          Graefes Arch Clin Exp Ophthalmol NEO YN, Martinez-Alvarez L, Davagnanam I, Girafa G, et al Treatment of post-vaccination optic neuritis: implications from the glob...

  Antiviral Res XIONG R, Wu Y, Wang Y, Qu Z, et al Rapid generation of a murine RSV infectious model by transducing a conditional knock-in mouse harboring human IGF1 receptor with adenoviral vector. Antiviral Res. 2025;244:106304. PubMed           Abstract available SUTTO-ORTIZ P, Selisko B, Ferron F, Sommadossi JP, et al Mapping the impact of 1'-, 2'- and 4'-nucleotide modifications on the Respiratory Syncytial Virus RNA-dependent RNA polymerase. Antiviral Res. 2025;244:106298. PubMed           Abstract available Biochem Biophys Res Commun MOHAMMED A, Ibrahim NA, Basher NS Innovations and challenges in vaccine development: Lessons from the SARS-CoV-2 pandemic and prospects. Biochem Biophys Res Commun. 2025;792:152947. PubMed           Abstract available J Gen Virol METAXAKI M, Ram R, Perera M, Wills M, et al Robust antibody and T cell responses tracked longitudin...

  Abstract Increase in human H5N1 spillover infections resulting from dissemination of highly pathogenic avian influenza (HPAI) virus into bird and mammal populations raises concerns about HPAI gaining human transmissibility . Studies identified hemagglutinin (HA) acid stability and receptor preference as essential traits that shape host tropism. Mutations that increase HA stability and affinity for α−2,6-linked sialic acids have been shown to confer airborne transmissibility in a ferret model , however mechanisms of activation of H5 subtype HA are poorly understood and the effect of adaptive mutations on HA function has been largely inferred from static structures. Here, we use hydrogen/deuterium-exchange mass spectrometry to dissect activation dynamics for two ancestral H5 HPAI HA , their transmission-adapted HA , and a contemporary HA . We identify variation in receptor binding site flexibility and demonstrate that adaptive mutations result in suppression of fusion peptide dynam...

  ABSTRACT The secondary thrombotic/vascular clinical syndrome of COVID-19 suggests that SARS-CoV-2 infects the endothelium ; however, robust in vitro infection of endothelial cells by various strains of SARS-CoV-2 remains to be demonstrated and continues to be debated. Here, we revisit the question of endothelial cell permissiveness to SARS-CoV-2 using isolated endothelial cells ( from the lung, aorta, and endothelial cell progenitors ), and additionally, to overcome limitations associated with cultured cells , using native endothelial cells within living precision cut human lung slices and single-cell RNA sequencing to track viral presence. Cellular infection in endothelial monocultures was determined using fluorescence imaging. Mediator release was measured by ELISA, and gene expression was assessed by RT-qPCR. Infection in lung slices was determined using single-cell RNA sequencing, capturing molecular identifiers that aligned to the SARS-CoV-2 viral genome (for lung slices). E...

  Highlights •  Fermentation of raw milk for 7 h at 42 °C to pH 4.4 reduced AIV levelsAIV by ≤ 4.1 log10 EID50. •  Incubation of raw milk for 7 h at 42 °C to pH 6.6 reduced levels by ≤ 4.3 log10 EID50. •  PH, temperature and/or bacterial degradation appreciably reduced AIV levels in raw milk. Abstract In March 2024, highly pathogenic avian influenza (HPAIV) H5N1 was first detected in U.S. dairy cattle and has since spread to herds across at least 17 states. Infected cows typically present with mastitis, decreased milk production, and poor milk quality with high viral loads in milk . While commercial pasteurization of milk effectively inactivates avian influenza virus (AIV), growing consumer interest in raw milk and derived products raises public health concerns due to the risk of zoonotic transmission . Standard yogurt production includes an initial heating step at 82 °C for 30 min to denature milk proteins which also inactivates AIV . However, some home yogurt recip...

  ABSTRACT Dromedary camels are the primary reservoir for Middle East respiratory syndrome coronavirus (MERS-CoV), a zoonotic coronavirus responsible for sporadic human infections . While clade B predominates in the Arabian Peninsula and is frequently linked to zoonotic outbreaks and household secondary transmission , clade C circulates primarily in African camels , with limited evidence of human infections . The extent of MERS-CoV transmission, genetic diversity, and cross-species potential in North Africa remains poorly characterized. Here, we investigate MERS-CoV incidence, seroprevalence, and genomic recombination in dromedary camels and sympatric livestock across slaughterhouses and farms in Egypt . MERS-CoV was detected in 12% of camels sampled at slaughterhouses , with no evidence of infection in cattle, buffalo, sheep, or goats . Seroprevalence was higher in slaughtered camels (79%) than camels on farms (12%). Phylogenetic analyses of MERS-CoV genomes obtained from dromedar...

  Abstract The spillover of H5N1 clade 2.3.4.4b into dairy cattle has raised concerns over the safety of fluid milk . While no foodborne infection has been reported in humans, this strain has infected at least 70 people and milk from infected cows is known to be infectious by ingestion in multiple other species. Investigation into the public health threat of this outbreak is warranted. This farm-to-table quantitative microbial risk assessment (QMRA) uses stochastic models to assess the risk of human infection from consumption of raw and pasteurized fluid cow's milk from the United States supply chains. These models were parameterized with literature emerging from this outbreak, then employed to estimate the H5N1 infection risk and evaluate multiple potential interventions aimed at reducing this risk. The median (5th, 95th percentiles) probabilities of infection per 240-mL serving of pasteurized, farmstore-purchased raw, or retail-purchased raw milk were 7.66E-19 (2.39E-20, 4.02E-17...

  {Excerpt} To the Editor : In March 2024, public health agencies in the United States reported highly pathogenic avian influenza (HPAI) virus of subtype A( H5N1 ) in dairy cattle , with virus detected in milk samples from symptomatic animals. Viral genetic fragments were subsequently found in pasteurized retail dairy products , which aroused concern about potential exposure through the human food supply . Heat treatment has been shown to reduce or eliminate infectious virus from both milk from infected cows and milk spiked with HPAI A(H5N1) virus. However, whether HPAI A(H5N1) virus in spiked milk from healthy cows replicates the properties of virus in milk from infected cows is unclear. We directly compared the stability of HPAI A(H5N1) virus in infected cows’ milk with that in spiked milk at 4°C (refrigeration temperature) and after heat treatment at 63°C (low-temperature, longer-duration pasteurization) or 72°C (high-temperature, shorter-duration pasteurization). (...) (...) So...

  Abstract Importance Since the early 2000s, companion animals emerged as unexpected players in influenza A virus ecology . Canine influenza viruses and the increasing detection of highly pathogenic avian influenza viruses in cats have raised concerns about their potential role as intermediate hosts for pandemic emergence . Their unique position at human-animal interface creates unprecedented opportunities for viral evolution and bidirectional transmission between humans and animals. Observations This review examined the transmission pathways and molecular adaptations of influenza A virus in companion animals. Cats primarily acquire infections through alimentary routes , including consumption of raw poultry and unpasteurized milk , as well as environmental exposure through hunting. Dogs transmit influenza viruses via respiratory droplets in high-density settings such as shelters and kennels . Canine influenza viruses demonstrate successful mammalian adaptation through accumulated m...

  Abstract Highly pathogenic avian influenza (HPAI) represents a threat to animal and human health, with the ongoing H5N1 outbreak within the H5 2.3.4.4b clade being one of the largest on record . However, it remains unclear what factors have contributed to its intercontinental spread . We use Bayesian additive regression trees , a machine learning method designed for probabilistic modelling of complex nonlinear phenomena , to construct species distribution models (SDMs) for HPAI clade 2.3.4.4b presence. We identify factors driving geospatial patterns of infection and project risk distributions across Europe . Our models are time-stratified to capture both seasonal changes in risk and shifts in epidemiology associated with the succession of H5N6/H5N8 by H5N1 within the clade . While previous studies aimed to model HPAI presence from physical geography, we explicitly consider wild bird ecology by including estimates of bird species richness, abundance of specific taxa, and “abundanc...

  Abstract This study assessed the epidemiological and microbiological invasive pneumococcal disease (IPD) changes that occurred before and after the emergence of COVID-19 in Italy . All IPD cases reported through the nationwide surveillance system during 2018–2023 were included. IPD incidence and serotype distributions were analyzed by age group. IPD incidence in 2020–2021 declined in all age groups compared with 2018–2019 , especially in children less than 2 years of age and elderly people aged > 64 years. A resurgence of IPD cases was observed from late 2022 onwards , with values in children exceeding those seen before the pandemic. The post COVID-19 increase in children was mainly driven by some PCV13 serotypes , such as 3, 19A, and 19F , but also non-vaccine serotypes, including 10A, 8, and 24F , while in the elderly population , a predominance of serotypes 3 and 8 was observed . In conclusion, a steep drop in IPD incidence was observed during the peak of the COVID-19 pande...

  Abstract The global spread of highly pathogenic avian influenza A(H5N1) viruses poses a serious pandemic threat . While sustained human-to-human transmission has not occurred, widespread circulation in birds , increased detection in mammals , and occasional human spillovers underscore the need for safe and effective vaccines . We evaluated an H5 mRNA vaccine candidate in ferrets using recent clade 2.3.4.4b A(H5N1) human isolates. Vaccination elicited strong neutralizing antibodies , conferred robust protection against lethal challenge , and significantly reduced viral titers . In a direct contact transmission model , mRNA vaccination decreased virus shedding in inoculated ferrets and reduced onward transmission ; it also protected vaccinated contact ferrets from infection following exposure to virus-shedding, unvaccinated ferrets. Additionally, sera from vaccinated animals cross-neutralized clade 2.3.2.1e human viruses to varying degrees, depending on the strain. These findings d...

  Abstract Highly pathogenic avian influenza (HPAI) H5 viruses have recently been documented in mammals including humans , posing a major threat to global public health . To prevent a potential H5 pandemic , it is critical to elucidate the antigenic evolutionary pattern and identify key drivers underlying its evolution . In this work, we construct a comprehensive antigenic map of H5 influenza viruses spanning their evolutionary history and classified three antigenic clusters with no cross-neutralization . The first corresponds to ancestral clades, the second to 2.3.4.4* clades being predominant since 2010, and the third to 2.3.4.4 h clade. Despite the gradually increasing genetic distances from ancestral to 2.3.4.4* to 2.3.4.4 h, their antigenic evolution does not follow the same progressive pattern: the antigenic distance between 2.3.4.4 h and ancestral is smaller than that between 2.3.4.4* and ancestral . This divergence is associated with two distinct mutation patterns at six ke...

  Abstract Laridae birds, such as gulls, are known reservoirs of H13 and H16 low pathogenic avian influenza subtypes . However, during the recent outbreaks linked to the reemergence of high pathogenicity avian influenza virus (HPAIV) H5N1 clade 2.3.4.4b of the Goose/Guangdong lineage, European populations of those birds suffered significant losses. HPAI cases were registered not only along the coastlines but also inland areas , particularly in France and Central Europe . During a diagnostic investigation of a group of Laridae birds , part of a HPAIV outbreak registered in the South of France in 2023, larval stages of Ornithodoros maritimus , a nidicolous soft tick parasitizing seabirds, were recovered from a slender-billed gull (Chroicocephalus genei). Affected birds exhibited gross and histopathological lesions consistent with systemic HPAI infection . Immunohistochemistry revealed marked neurotropism , oculotropism and multicentric epitheliotropism . Viral isolation and sequencin...

  BMJ Analysis of peer reviewers' response to invitations by gender and geographical region: cohort study of manuscripts reviewed at 19 biomedical journals before and during covid-19 pandemic. BMJ. 2025;391:r2507. PubMed          Clin Infect Dis NGUYEN VAN JC, Pilmis B, El Helali N, Azria E, et al Implementing POCT in infectious diseases. Clin Infect Dis. 2025 Nov 27:ciaf650. doi: 10.1093. PubMed           Abstract available PANAGIOTOPOULOS AP, Anastassopoulou C, Tsakris A, Ioannidis JPA, et al Effective Antivirals in Pandemic Preparedness: Past Mistakes, Future Needs. Clin Infect Dis. 2025 Nov 25:ciaf648. doi: 10.1093. PubMed           Abstract available Int J Infect Dis HEMPEL H, Xue H, La Shu S, Jain S, et al Cancer and COVID-19: A review of Immune Insights and Partnerships to Inform Public Health Strategy. Int J Infect Dis. 2025 Nov 24:108252. doi: 10.1016/j.ijid.2...

  BMC Pediatr KIM S, Talluri R, Yu A, Evans M, et al The effect of the COVID-19 pandemic on racial disparities in suicide and homicide by firearm rates in Missouri. BMC Pediatr. 2025;25:953. PubMed           Abstract available Epidemiol Infect CHUA H, Tsang TKL, Lee SL, Chan ELY, et al Waning in influenza vaccine effectiveness against influenza A(H1N1)pdm09-associated hospitalization in children in 2012/13. Epidemiol Infect. 2025 Nov 24:1-25. doi: 10.1017/S0950268825100770. PubMed          J Infect Dis ZHANG X, Lam SJ, Chen LL, Fong CH, et al Avian influenza virus A(H5N1) genotype D1.1 is better adapted to human nasal and airway organoids than genotype B3.13. J Infect Dis. 2025 Nov 24:jiaf598. doi: 10.1093. PubMed           Abstract available J Virol MITCHELL JK, Mastrodomenico V, Hartnett J, Heelan WJ, et al A HiBiT-tagged pseudovirus-like particle platform for safe, ...