A Phase 1/2 Dose-Ranging Safety and Immunogenicity Study of #mRNA-Based Candidate #Pandemic #Influenza #Vaccines in Healthy Adults

 

Abstract

Background

Influenza A viruses pose a persistent pandemic threat. We report safety, reactogenicity, and immunogenicity findings for mRNA-1018 pandemic influenza vaccine candidates from a phase 1/2 study in healthy adults.

Methods

In Part A, participants were randomized to receive 1 of 4 mRNA-1018 candidates at 1 of 3 dose levels across 2 influenza A groups: (1) H5N8/H5-only or (2) H7N9/H7-only. H5N8 and H7N9 candidates were administered at 25, 50, or 100-µg and H5-only and H7-only at 12.5, 25, or 50-µg. Part B participants were randomized to receive 12.5, 25, or 50-µg H5-only-CG. Primary objectives were to evaluate the safety and reactogenicity of vaccine candidates. Secondary objectives included evaluation of humoral immunogenicity through day 205 by hemagglutination inhibition (HAI), neuraminidase inhibition, and microneutralization assays.

Results

Parts A and B comprised 1195 and 304 dosed participants, respectively. Overall, solicited local adverse reactions (ARs) within 7 days of vaccination occurred in 76.8% of participants across vaccine candidates and dose levels, most commonly injection-site pain. Solicited systemic ARs were reported in 62.8% of participants, most frequently fatigue and headache. Solicited ARs were predominantly grade 1–2 in severity, with few grade 3 and no grade 4 events. Post-vaccination immune responses, assessed absolutely, by HAI titers and dynamically, by seroconversion rates, tended to increase with vaccine dose. H5-based candidates induced stronger strain-specific HAI, but with comparable microneutralization titers, versus H7-based candidates.

Conclusions

Vaccine candidates were sufficiently well-tolerated and immunogenic. Further development of mRNA pandemic influenza vaccines is warranted for pandemic preparedness.

Source: 

Link: https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciag278/8662346

____

#Coronavirus Disease Research #References (by AMEDEO, April 25 '26)

 

Ann Intern Med

1. FRITZ JM, Skolasky RL, Brennan G, Minick K, et al
   Effectiveness of Nonpharmacologic Treatments for Chronic Low Back Pain : A Sequential, Multiple-Assignment, Randomized Trial.
   Ann Intern Med. 2026 Apr 21. doi: 10.7326/ANNALS-25-04645.
   PubMed         Abstract available
   
   

   
   Clin Infect Dis

2. BAKER JV, Siegel L, Losso M, Vasudeva S, et al
   Ensitrelvir for the treatment of hospitalized adults with COVID-19: an international phase 3 randomized placebo-controlled trial.
   Clin Infect Dis. 2026 Apr 22:ciag272. doi: 10.1093.
   PubMed         Abstract available
   
   

   
   Int J Infect Dis

3. ZHAO CY, Wang FS, Jiao YM
   SARS-CoV-2 infection disrupts the immune control status in a male HIV-1 elite controller.
   Int J Infect Dis. 2026 Apr 20:108713. doi: 10.1016/j.ijid.2026.108713.
   PubMed         Abstract available
   
   

   
   J Infect

4. BEHARIER O, Guedalia J, Sehtman-Shachar DR, Kerem L, et al
   Maternal SARS-CoV-2 Infection and Early Child Growth and Development: A Nationwide Cohort Study.
   J Infect. 2026 Apr 17:106749. doi: 10.1016/j.jinf.2026.106749.
   PubMed         Abstract available
   
   

   
   J Med Virol

5. HO SY, Liu YC, Ho SY, Chen SH, et al
   Emergence of Echovirus 11 in Severe and Neonatal Enterovirus Infections: A 9-Year Retrospective Study in Taiwan Before and After the COVID-19 Pandemic.
   J Med Virol. 2026;98:e70929.
   PubMed         Abstract available
   
   
6. AVILA JP, Park P, Singh Y, Amaral PP, et al
   Multiorgan Molecular Landscape of Severe COVID-19 Revealed by Consensus Gene Signatures and RAB8B Targeting.
   J Med Virol. 2026;98:e70932.
   PubMed         Abstract available
   
   
7. KESKIN S, Pavel STI, Sak R, Bahadori F, et al
   Modified mRNA Encoding the Crimean-Congo Hemorrhagic Fever Virus Nucleocapsid Protein Confers Robust Protection Against Lethal Challenge in Mice.
   J Med Virol. 2026;98:e70940.
   PubMed         Abstract available
   
   

   
   J Virol

8. SALISCH F, Muller-Ruttloff C
   Behind the membranous curtain-lipid dynamics and functions in coronaviral replication.
   J Virol. 2026 Apr 21:e0175325. doi: 10.1128/jvi.01753.
   PubMed         Abstract available
   
   
9. YANG M, Zhao Y, Guo W, Wang L, et al
   Development of a vaccine based on mRNA assembly of PEDV virus-like particle.
   J Virol. 2026 Apr 21:e0206025. doi: 10.1128/jvi.02060.
   PubMed         Abstract available
   
   
10. ZHANG K, Wang S, Kang X, Li F, et al
    Swine GBP1 restricts PDCoV replication via disrupting the replication and transcription complex formation.
    J Virol. 2026 Apr 21:e0020726. doi: 10.1128/jvi.00207.
    PubMed         Abstract available
    
    
11. ZHAO J, Tian J, Zhang L, Li Y, et al
    Coronavirus infectious bronchitis virus spike protein inhibits FUNDC1-mediated mitophagy to prevent nucleocapsid protein degradation.
    J Virol. 2026 Apr 20:e0180025. doi: 10.1128/jvi.01800.
    PubMed         Abstract available
    
    
12. MU S, Bai Y, Qiu R, Zhang F, et al
    Porcine hemagglutinating encephalomyelitis virus nucleocapsid protein targets RIG-I and IRF3 to evade IFN immunity.
    J Virol. 2026 Mar 30:e0211225. doi: 10.1128/jvi.02112.
    PubMed         Abstract available
    
    
13. ZHANG X, Li Y, Yuan J, Li Q, et al
    Metformin hydrochloride regulates glycolysis and inhibits PEDV replication by inhibition of PI3K-AKT signaling pathway.
    J Virol. 2026;100:e0014726.
    PubMed         Abstract available
    
    

    
    JAMA

14. LEFF B, Siu A, DeCherrie LV, Levine DM, et al
    Hospital at Home and Transforming US Health Care Delivery.
    JAMA. 2026 Apr 23. doi: 10.1001/jama.2026.4791.
    PubMed        
    
    
15. KUKOYI OM, Wang VS, Yao K, Cipriano CB, et al
    US State Actions Related to COVID-19 Vaccination Infrastructure and Access Amid Federal Shifts.
    JAMA. 2026 Apr 20:e265148. doi: 10.1001/jama.2026.5148.
    PubMed        
    
    

    
    Lancet Infect Dis

16. ZHANG L, Hoffmann M, Pohlmann S
    Does BA.3.2 epidemiology imply a change in SARS-CoV-2 evolution?
    Lancet Infect Dis. 2026 Apr 17:S1473-3099(26)00192.
    PubMed        
    
    

    
    N Engl J Med

17. BUTLER CC, Pinto AD, Harris V, Holmes J, et al
    Oral Nirmatrelvir-Ritonavir for Covid-19 in Higher-Risk Outpatients.
    N Engl J Med. 2026;394:1583-1594.
    PubMed         Abstract available
    
    

    
    Nature

18. GALLO G, Di Nardo A, Lugano D, Roberts AJ, et al
    Heart-nosed bat alphacoronaviruses use human CEACAM6 to enter cells.
    Nature. 2026 Apr 22. doi: 10.1038/s41586-026-10394.
    PubMed         Abstract available
    
    
19. YAN H
    A bat coronavirus can enter human cells through a previously unknown gateway.
    Nature. 2026 Apr 22. doi: 10.1038/d41586-026-00908.
    PubMed        

#Influenza and Other Respiratory Viruses Research #References (by AMEDEO, April 25 '26)

 

Ann Intern Med

1. LIM SY, Lee J, Chang E, Kwon JS, et al
   Neither Metformin nor Ursodeoxycholic Acid Effectively Treats Postacute Sequelae of COVID-19 : A Randomized Clinical Trial.
   Ann Intern Med. 2026 Mar 3. doi: 10.7326/ANNALS-25-04883.
   PubMed         Abstract available
   
   
2. QASEEM A, Obley AJ, Yost J, Abraham GM, et al
   Outpatient Treatment of Confirmed COVID-19 in Symptomatic Adults: Living, Rapid Practice Points From the American College of Physicians (Version 3).
   Ann Intern Med. 2026 Feb 10. doi: 10.7326/ANNALS-25-03766.
   PubMed         Abstract available
   
   
3. SOMMER I, Dobrescu A, Gadinger A, Sharifan A, et al
   Outpatient Treatment of Confirmed COVID-19: A Living, Rapid Review for the American College of Physicians (Version 3).
   Ann Intern Med. 2026 Feb 10. doi: 10.7326/ANNALS-25-03691.
   PubMed         Abstract available
   
   

   
   Biochemistry

4. MEDEIROS-SILVA J, Zhang Y, Hong M
   Phosphatidylinositol Interactions with the SARS-CoV-2 Envelope Protein Investigated by Lipid (13)C Labeling and Solid-State NMR.
   Biochemistry. 2026;65:1178-1191.
   PubMed         Abstract available
   
   

   
   J Infect

5. COX SN, Bennett JC, Casto AM, Hoffman KL, et al
   INFLUENZA HOUSEHOLD TRANSMISSION AND GENOMIC DIVERSITY IN THE UNITED STATES: A PROSPECTIVE COHORT STUDY, 2022-2024.
   J Infect. 2026 Apr 20:106748. doi: 10.1016/j.jinf.2026.106748.
   PubMed         Abstract available
   
   

   
   J Virol

6. ZHANG R, Jian X, Zhang Y, Sun Y, et al
   The oral nucleoside analogue inhibitor VV251 effectively inhibits coinfection by respiratory syncytial virus and influenza A virus.
   J Virol. 2026 Apr 21:e0000626. doi: 10.1128/jvi.00006.
   PubMed         Abstract available
   
   
7. YILDIZ S, El Zahed SS, Villalon-Letelier F, Wang Q, et al
   Re-engineering segment 8 facilitates generation of a versatile live-attenuated influenza A virus vector platform for secretory protein delivery.
   J Virol. 2026 Apr 21:e0034726. doi: 10.1128/jvi.00347.
   PubMed         Abstract available
   
   
8. KONG W, Zhang J, Song Y, Song J, et al
   Disruption of spike protein N-glycosylation induces its endoplasmic reticulum retention and attenuates SARS-CoV-2 infectivity.
   J Virol. 2026 Mar 30:e0027026. doi: 10.1128/jvi.00270.
   PubMed         Abstract available
   
   
9. XIU R, Wang Y, Cai W, Wang Q, et al
   Potent in vitro synergistic antiviral effects of the pan-coronavirus fusion inhibitor EK1 in combination with RBD-specific antibodies or M(pro) inhibitors.
   J Virol. 2026 Mar 30:e0007626. doi: 10.1128/jvi.00076.
   PubMed         Abstract available
   
   
10. BRENNAN JW, Wang G, Connor S, Wang X, et al
    A respiratory syncytial virus trailer sequence modulates viral replication and the generation and propagation kinetics of copy-back defective viral genomes.
    J Virol. 2026;100:e0018426.
    PubMed         Abstract available
    
    
11. ADAM A, Wu W, Jones MC, Hao H, et al
    Respiratory syncytial virus infection induces heterologous protection against SARS-CoV-2 through gammadelta T cell-mediated trained immunity and the activation of SARS-CoV-2-reactive mucosal T cells.
    J Virol. 2026 Mar 18:e0165825. doi: 10.1128/jvi.01658.
    PubMed         Abstract available
    
    

    
    MMWR Morb Mortal Wkly Rep

12. BELL JM, Barbre K, Meng L, Lape-Newman B, et al
    Influenza Vaccination Coverage Among Nursing Home Residents and Health Care Personnel - United States, 2024-25 Influenza Season.
    MMWR Morb Mortal Wkly Rep. 2026;75:195-201.
    PubMed         Abstract available
    
    

    
    N Engl J Med

13. BUTLER CC, Pinto AD, Harris V, Holmes J, et al
    Oral Nirmatrelvir-Ritonavir for Covid-19 in Higher-Risk Outpatients.
    N Engl J Med. 2026;394:1583-1594.
    PubMed         Abstract available
    
    

    
    Pediatrics

14. SEGEV N, Wilson E, Moehlman M, Corathers SD, et al
    Unmasking Adrenal Insufficiency: Adrenal Crisis Triggered by Influenza-Associated Encephalitis.
    Pediatrics. 2026 Apr 22:e2025072983. doi: 10.1542/peds.2025-072983.
    PubMed         Abstract available
    
    

    
    PLoS Comput Biol

15. LI Y, Nielsen BF, Levin SA, Te Velthuis AJW, et al
    Spatio-temporal modelling of in vitro influenza A virus infection: The impact of defective interfering particles on the type I interferon response.
    PLoS Comput Biol. 2026;22:e1014198.
    PubMed         Abstract available
    
    
16. WHITE LA, Leon TM
    Forecastability of infectious disease time series: are some seasons and pathogens intrinsically more difficult to forecast?
    PLoS Comput Biol. 2026;22:e1014175.
    PubMed         Abstract available
    
    

    
    PLoS One

17. ORTEGA-MARTIN E, Alvarez-Galvez J
    Understanding quality-of-life patterns in long COVID: How Symptoms and socioeconomic conditions shape patient wellbeing.
    PLoS One. 2026;21:e0347743.
    PubMed         Abstract available
    
    
18. CHAVES SS, Castells VB, Mira-Iglesias A, Puig-Barbera J, et al
    Rhinovirus/enterovirus contribution to respiratory-associated hospitalizations in adults during respiratory seasons in Spain: A 6-year prospective study.
    PLoS One. 2026;21:e0347659.
    PubMed         Abstract available
    
    
19. LEE J, Bajiya VP, Jung E
    Vaccination scenario-based study on seasonal influenza in Republic of Korea.
    PLoS One. 2026;21:e0322686.
    PubMed         Abstract available
    
    
20. PIRZADA P, Wilde A, Doherty GH, Harris-Birtill D, et al
    Understanding older adults' perception, acceptance, and adoption of smart home technologies.
    PLoS One. 2026;21:e0345563.
    PubMed         Abstract available
    
    
21. FANG Z, Xu H, Mu Y
    Risk-taking responses to crash experience: Evidence from China.
    PLoS One. 2026;21:e0347543.
    PubMed         Abstract available
    
    
22. GARZA J, Sebastian R, Cover B, Sanchez A, et al
    Nicotine dependence among critically ill COVID-19 patients: A population-based cohort study.
    PLoS One. 2026;21:e0308776.
    PubMed         Abstract available
    
    
23. MCDONALD C, Grajales AG, Yahia NA, Fisman D, et al
    Healthcare resource utilization and cost burden of COVID-19 according to vaccination status in adults in Ontario, Canada, 2021-2023.
    PLoS One. 2026;21:e0344690.
    PubMed         Abstract available
    
    
24. LOVATO N, Appleton SL, Reynolds AC, Gill TK, et al
    Relationships between pre-pandemic mental health, sociodemographic factors and health behaviours in older adults during the acute onset of COVID-19 in Australia: A descriptive analysis.
    PLoS One. 2026;21:e0346787.
    PubMed         Abstract available
    
    
25. AUDUREAU E, Jean C, Layese R, Neuraz A, et al
    Association between parenthood and survival among 30,386 patients hospitalized with COVID-19.
    PLoS One. 2026;21:e0346679.
    PubMed         Abstract available
    
    
26. IPEKCI AM, Hodel EM, Filsinger M, Wegmuller S, et al
    Who would take part in a pandemic preparedness cohort study? The role of vaccine-related affective polarisation: Cross-sectional survey.
    PLoS One. 2026;21:e0346420.
    PubMed         Abstract available
    
    
27. YANG Z, Imouza A, Puelma Touzel M, Amadoro C, et al
    Regional and temporal patterns of partisan polarization during the COVID-19 pandemic in the United States and Canada.
    PLoS One. 2026;21:e0347327.
    PubMed         Abstract available
    
    

    
    Proc Natl Acad Sci U S A

28. SANDERS CG, Liu M, Fusco JA, Ohl EM, et al
    Efficient replication of influenza D virus in the human airway underscores zoonotic potential.
    Proc Natl Acad Sci U S A. 2026;123:e2530325123.
    PubMed         Abstract available
    
    

    
    Vaccine

29. ROBERTSON AH, Wolf AS, Fossum E, Solum G, et al
    Long-lasting cross-reactive and polyfunctional SARS-CoV-2 T cell responses in seniors are maintained after repeated vaccination and infections.
    Vaccine. 2026;80:128511.
    PubMed         Abstract available
    
    
30. DLOUHY P, Petras M, Lesna IK, Macalik R, et al
    Transient elevation of NT-proBNP after mRNA COVID-19 vaccination in healthy adults: A longitudinal biomarker analysis.
    Vaccine. 2026;80:128535.
    PubMed         Abstract available
    
    
31. VAN DE BURGWAL LHM, Pronker ES, Herz J
    Australia's vaccine legacy: Time for a boost? Mapping an innovation system in a fragmented data environment.
    Vaccine. 2026;80:128525.
    PubMed         Abstract available
    
    
32. WU D, Liu K
    Cost and effectiveness of COVID-19 vaccination strategies during the 2023 post-reopening omicron wave in Xinjiang, Western China: Evidence from SIR and Markov models.
    Vaccine. 2026;80:128536.
    PubMed         Abstract available
    
    
33. MAEDA H, Saito N, Igarashi A, Ishida M, et al
    Effectiveness of JN.1-adapted COVID-19 vaccine against medically attended SARS-CoV-2 infection and COVID-19 hospitalization in adults in Japan, from October 2024 to April 2025: VERSUS.
    Vaccine. 2026;80:128544.
    PubMed         Abstract available
    
    
34. MORO PL, Romanson B, Marquez P, Zhang B, et al
    Adverse events after Pfizer's Respiratory Syncytial Virus Vaccine in pregnant women in the Vaccine Adverse Event Reporting System, 2024-2025, United States.
    Vaccine. 2026;80:128547.
    PubMed         Abstract available
    
    
35. QUINTANAR-SOLARES M, Fleming JA, Musau W, Mulati F, et al
    RSV ready? Exploring feasibility and acceptability of RSV immunization options in low- and middle-income countries.
    Vaccine. 2026;80:128550.
    PubMed         Abstract available
    
    
36. KITANO T, Hashimoto E, Sado T, Yoshida S, et al
    Maternal effectiveness of respiratory syncytial virus using multicenter healthcare records: A retrospective cohort study.
    Vaccine. 2026;80:128566.
    PubMed         Abstract available
    
    
37. ZHANG L, Lin T, Wang M, Ma X, et al
    Effectiveness of prescription-based influenza vaccination services among older adults in Binzhou, China: A cluster-randomized controlled trial.
    Vaccine. 2026;82:128588.
    PubMed         Abstract available
    
    
38. FOLEGATTI PM, Pepin S, Tabar C, Fries K, et al
    Immunogenicity and safety of recombinant influenza vaccine versus standard inactivated influenza vaccine in children aged 3 to 8 years: results from a phase III randomised study.
    Vaccine. 2026;82:128582.
    PubMed         Abstract available
    
    
39. RICE E, Cheng AC, Britton PN, Carr J, et al
    Influenza epidemiology, treatment and prevention in Australian children: Trends from 6 years of PAEDS-FluCAN influenza surveillance (2019-2024).
    Vaccine. 2026;82:128592.
    PubMed         Abstract available

#Prion shedding is reduced by chronic wasting disease {#CWD} #vaccination

 

Abstract

Chronic wasting disease (CWD) is a strictly fatal and highly contagious prion disease of wild and farmed cervids currently expanding in North America. Prion diseases are caused by conversion of the cellular prion protein to its pathological isoform PrPSc. Vaccination is considered a promising strategy to contain CWD, even though prion diseases do not show classical immune responses. For CWD containment, it is important that vaccines reduce shedding of prions in excreta, a major contributor to transmission. Here, we tested the effect of vaccines on prion shedding in feces and urine by vaccinating and prion infecting knock-in mice that recapitulate CWD pathogenesis as found in cervids. Vaccination reduced or even prevented CWD shedding in feces and urine collected between 30–90% of incubation time to disease. This is the first report showing that prion shedding can be blocked in a prion disease. For CWD specifically it may reduce the environmental prion burden and break the disease transmission cycle.

Source: 

Link: https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014166

____

Detection of a #Merbecovirus with potential #ACE2 usage in #France

 

ABSTRACT

A novel Merbecovirus, designated Cam-2023, has been identified in Pipistrellus pipistrellus in France through non-invasive surveillance. Phylogenetic analysis demonstrates that Cam-2023 belongs to a Merbecovirus clade previously associated with ACE2 usage in closely related viruses detected in the Netherlands and Russia. While the receptor usage of Cam-2023 remains to be functionally validated, sequence similarities within the Spike protein, particularly the receptor-binding domain, suggest a putative association with a Merbecovirus clade previously associated with ACE2 usage. This discovery broadens the known host diversity of this lineage and extends its geographical range to Western Europe. Our findings highlight the importance of continuous surveillance in European bat populations to better characterize the distribution and zoonotic potential of such high-risk coronaviruses.

Source: 

Link: https://www.tandfonline.com/doi/full/10.1080/22221751.2026.2651469

____

Robustly Quantifying #Uncertainty in #International Avian #Influenza #H5N1 Infection #Fatality Ratios

 

Abstract

Knowing the mortality rates associated with infection by a pathogen is essential for effective preparedness and response. Here, harnessing the flexibility of a Bayesian approach, we produce an estimate of the Infection Fatality Ratio (IFR) for A(H5N1) conditional on explicit assumptions, and quantify the uncertainty thereof. We also apply the method to first-wave COVID-19 data up to March 2020, demonstrating the estimates that could be obtained were the model available then. Our analysis uses World Development Indicators (WDI) from the World Bank, the A(H5N1) WHO confirmed cases and deaths tracker by country (2003-2024), and COVID-19 cases and deaths data from John Hopkins University (January and February 2020). Since infectious disease dynamics are typically influenced by local socio-economic factors rather than political borders, individual countries are placed within clusters of countries sharing similar WDIs relevant to respiratory viral diseases, with clusters derived by performing Hierarchical Clustering. To estimate the IFR, we fit a Negative Binomial Bayesian Hierarchical Model for A(H5N1) and COVID-19 separately. We explicitly modelled key unobserved parameters with informative priors from expert opinion and literature. By modelling underreporting, our analysis suggests lower fatality (15.3%) compared to WHO's Case Fatality Ratio estimate (54%) on lab-confirmed cases. However, credible intervals are wide ([0.5%, 64.2%] 95% CrI). Therefore, good preparedness for a potential A(H5N1) pandemic implies adopting scenario planning under our central estimate, as well as for IFRs as high as 70%. Our approach also returns a COVID-19 IFR estimate of 2.8% with [2.5%, 3.1%] 95% CrI which is consistent with literature.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

MKA is supported by the Schlumberger Foundation Faculty for the Future. TH is supported by the Wellcome Trust (Ref: 227438/Z/23/Z) and Medical Research Council (Ref: UKRI483). LG, MN, TF are employed by UKHSA. The research leading to these results received UK Government grant-in-aid funding to UKHSA. The views expressed in this publication are those of the authors and not necessarily those of UKHSA or Department for Health and Social Care. 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/10.64898/2026.04.22.26351373v1

____

An #NS1-F161L #Substitution Determines #Host-Driven #Virulence Enhancement of #H5N6 Avian #Influenza Virus in #Ducks

 

Abstract

H5 subtype avian influenza virus (AIV) can infect both chickens and ducks, leading to substantial economic losses. Nevertheless, certain strains cause silent infections in ducks. In this study, a goose-origin clade 2.3.4.4h H5N6 AIV was isolated, which caused high mortality in mixed-gender white leghorn chickens but no deaths in mixed-gender mallard ducks. After independent serial in vitro passage in duck embryo fibroblasts (DEFs) and in vivo passage in specific-pathogen-free (SPF) ducks, the DEF-passage 10 (P10) virus induced markedly higher mortality rates and viral loads in SPF ducks compared to the DEF-P1 virus and the original parental virus prior to passage. Similarly, the in vivo-passaged P3 and P4 viruses exhibited significantly higher mortality rates than the P1 virus in SPF ducks, with 100% mortality and markedly increased viral titers in the organs. A whole-genome SNP analysis identified seven high-frequency mutations in the M1, NA and NS1 proteins. The NS1-F161L substitution virus exhibited significantly increased mortality rates, viral loads in multiple tissues, and a robustly induced innate immune response in ducks. Furthermore, dynamic evolutionary variations in the NS1 protein among global H5 avian influenza viruses revealed that the NS1-F161L substitution became dominant in clade 2.3.4.4b viruses in 2021 and subsequent years. Collectively, our findings demonstrate that host-driven adaptation can rapidly increase the pathogenicity of H5N6 AIVs in ducks and identify NS1-F161L as a critical virulence marker. These results offer novel insights relevant to the molecular surveillance, virulence prediction, and risk assessment of circulating H5 AIVs in waterfowl.

Source: 

Link: https://www.mdpi.com/1999-4915/18/5/488

____

Longitudinal #serum #proteomics analyses reveal #biomarkers for porcine #influenza and #coronavirus infections

 

Abstract

Respiratory virus infections affect both humans and livestock, causing considerable mortality and morbidity. While respiratory pathogens such as swine influenza A virus (pH1N1) and porcine respiratory coronavirus (PRCV) often present with overlapping clinical symptoms, their pathological trajectories and outcomes differ. Given the propensity for pathogen spillover and the use of pigs as a physiologically relevant large-animal translational model, we aimed to characterise host serum protein signatures that detect and differentiate pH1N1 from PRCV, enabling improved disease monitoring and control. Using high-resolution mass spectrometry-based proteomics, we identified 162 serum proteins that were significantly dysregulated across 3 infection timepoints (1, 5, and 12 days post-infection (DPI)), with signatures correlating with viral shedding and lung pathology as early as 1 DPI. Notably, multiplexed targeted analysis of a subset of proteins in an independent cohort from a different breed and geographic location demonstrated detection, femtomole-level targeted quantitation, and validation of SRGN as a diagnostic marker for pH1N1 and PRCV (AUC=0.85). Further, SOD1 was validated as an early marker for PRCV, increasing as early as 1 DPI (AUC= 0.9). Finally, a multi-peptide signature composed of SRGN, SOD1, and RAN demonstrated reasonable predictive power for pH1N1 (AUC=0.75) and PRCV (AUC=0.65) at 1 DPI. Our data validate the proteomic screening, provide insights into the role of early protein markers in distinguishing respiratory viral infections, and pave the way for the development of point-of-care diagnostics and targeted prevention strategies, enhancing preparedness against emerging zoonotic threats.

Competing Interest Statement

The authors have declared no competing interest.

Funder Information Declared

UKRI Biotechnology and Biological Sciences Research Council (BBSRC), BB/X019780/1, BBS/E/PI/230002A, BBS/E/PI/230002B, BBS/E/PI/230002C, BS/E/PI/23NB0004

University of Surrey, https://ror.org/00ks66431

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.04.21.719833v1

____

Heterologous Sequential #mRNA #Vaccination of Indian Rhesus #Macaques Elicits Broad Binding and Neutralizing #Antibody Responses Against Diverse #Henipaviruses

 

Abstract

Henipaviruses (HNVs), including Nipah virus (NiV) and Hendra virus (HeV), are highly pathogenic and often lethal zoonotic viruses with broad species tropism and no approved human vaccines. The emergence of genetically divergent HNVs—including Ghana virus (GhV), Langya virus (LayV), and Mojiang virus (MojV)—emphasizes the need for broadly protective countermeasures. Here, we evaluated the antibody (Ab) responses to sequential mRNA vaccines encoding the membrane-bound attachment glycoprotein (gG) from NiV, GhV, and/or LayV in a pilot study with Indian rhesus macaques. Serum binding Ab responses were quantified by ELISA against five soluble gG antigens (NiV, HeV, GhV, LayV, MojV). Functional activity was assessed by neutralization assays using NiV, HeV, and GhV pseudoviruses, and by receptor-blocking ELISA. Sequential vaccination induced high-titer IgG binding against all five HNV gGs with increasing breadth after each dose. Pan-genus regimens elicited moderate neutralizing Ab titers against NiV, HeV, and GhV, whereas the NiV-only regimen elicited potent but narrow neutralization against NiV and HeV. Conversely, the GhV-LayV-GhV regimen elicited strong binding to GhV, LayV, and MojV gG and robust neutralization of GhV pseudovirus, but limited cross-reactivity to NiV and HeV. In this pilot study, we demonstrated that mRNA vaccination can elicit broadly reactive binding and neutralizing Ab responses across phylogenetically distant HNVs. Additionally, we show GhV pseudovirus neutralization for the first time. Collectively, these data provide a foundation for the development of next-generation pan-genus HNV vaccines capable of mitigating future HNV outbreaks.

Source: 

Link: https://www.mdpi.com/1999-4915/18/5/487

____

#Nosocomial #outbreak of #Lassa fever in Conakry, #Guinea, 2022

 

Abstract

Background

Lassa fever (LF) is endemic in Guinea, with high seroprevalence in the forest region. However, clinical cases have been only anecdotally reported. In August 2022, a nosocomial outbreak occurred at a private clinic in the capital Conakry, an area previously considered low risk.

Methods

Suspected cases were confirmed by real-time RT-PCR within 24 hours. Viremia was monitored during hospitalization, and whole-genome sequencing was performed in-country within 13 days of outbreak detection. Outbreak investigation involved rodent testing in the home village of the suspected primary case.

Results

Six cases were laboratory-confirmed, five of which were healthcare workers of the clinic. The case fatality rate was 16.7%. Viral RNA remained detectable in blood of survivors for a median of 26 days (IQR 24-41) post disease onset. Epidemiological investigations identified a suspected primary case, who had died of a febrile disease compatible with Lassa fever, had contact with all secondary cases, and had a travel history from Kissidougou area. Three near-complete and one partial Lassa virus genomes were recovered from the secondary cases, which phylogenetically clustered with genomes from central Guinea. Consistent with a common transmission source, the four genomes were almost identical. Rodent testing revealed a new reservoir area in eastern-central Guinea.

Discussion

This outbreak highlights the vulnerability of healthcare settings in low-prevalence areas of West Africa to nosocomial Lassa virus transmission due to human mobility. Facilitated by capacity building programs for viral hemorrhagic fevers, rapid diagnosis, genomic analysis, and ecological assessment enabled an efficient outbreak response and control.

Source: 

Link: https://academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiag229/8661158

____

Oral #Nirmatrelvir – Ritonavir for #Covid19 in Higher-Risk #Outpatients

 

Abstract

Background

Nirmatrelvir–ritonavir has been shown to reduce progression to severe illness from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in unvaccinated high-risk outpatients. The effectiveness of nirmatrelvir–ritonavir in persons who have been vaccinated, infected naturally, or both is unclear.

Methods

In two open-label platform trials (PANORAMIC in the United Kingdom and CanTreatCOVID in Canada), we enrolled higher-risk adults (≥50 years of age or ≥18 years of age with coexisting conditions) in the community who tested positive for SARS-CoV-2 and had been unwell for 5 days or less. The participants were randomly assigned to receive usual care plus nirmatrelvir (300 mg)–ritonavir (100 mg) twice a day for 5 days or to receive usual care alone. The primary outcome was hospitalization or death from any cause within 28 days after randomization.

Results

From December 8, 2021, to September 30, 2024, a total of 3516 participants in the PANORAMIC trial and 716 participants in the CanTreatCOVID trial underwent randomization. In the PANORAMIC trial, 14 of 1698 participants (0.8%) in the nirmatrelvir–ritonavir group and 11 of 1673 participants (0.7%) in the usual-care group were hospitalized or died (adjusted odds ratio, 1.18; 95% Bayesian credible interval, 0.55 to 2.62; probability of superiority, 0.334). In the CanTreatCOVID trial, 2 of 343 participants (0.6%) in the nirmatrelvir–ritonavir group and 4 of 324 participants (1.2%) in the usual-care group were hospitalized or died (adjusted odds ratio, 0.48; 95% Bayesian credible interval, 0.08 to 2.23; probability of superiority, 0.830). In a substudy involving 634 participants, viral load was reduced by the end of treatment with nirmatrelvir–ritonavir. Serious adverse events with nirmatrelvir–ritonavir were reported in 9 participants in the PANORAMIC trial and in 4 participants in the CanTreatCOVID trial.

Conclusions

In two open-label trials, nirmatrelvir–ritonavir did not reduce the incidence of hospitalization or death among vaccinated higher-risk participants with SARS-CoV-2 infection. (Funded by the National Institute for Health and Care Research, and others; PANORAMIC ISRCTN number, 2021-005748-31; CanTreatCOVID ClinicalTrials.gov number, NCT05614349.)

Source: 

Link: https://www.nejm.org/doi/full/10.1056/NEJMoa2502457?query=TOC

____

The ‘Spanish’ #influenza #pandemic: new #evidence for influenza #outbreaks in #England and #France prior to 1918

 

Abstract

The Spanish influenza pandemic of 1918 caused well over fifty million deaths. The epicentre undoubtedly was China, where gene mixing of different virus strains occurred amongst aquatic, migrant birds. But where and when did the virus first infect (or spill over to) a human being? We take, as our starting point, a paper demonstrating that an infection causing the same symptoms as the influenza virus was widespread in New York during the winter of 1917–1918. The authors of that paper went on to suggest that the virus had probably reached North America from Europe, in the context of troop movement during World War I. Our own researches have focussed on this point. We show that outbreaks of serious respiratory disease, local in nature but causing unusual patterns of mortality, were indeed reported by scientists and doctors in army hospitals in England and in France, well before the first wave of the pandemic had arrived. We use the records of these hospitals, now held in the National Archives, to trace the progress of this disease amongst the individuals who fell ill. We examine contemporary reactions to this minor epidemic – an epidemic, we suggest, which acted as a herald wave of the pandemic yet to come. The latter part of our paper addresses the second question, as to how troop movement across the North Atlantic, once the United States had entered into war, may well have enabled the virus to spread from Europe to North America.

Source: 

Link: https://www.cambridge.org/core/journals/medical-history/article/spanish-influenza-pandemic-new-evidence-for-influenza-outbreaks-in-england-and-france-prior-to-1918/8BC01CCE54683ED7A4DD1DFF0C3AE7EA

____

Heart-nosed #bat #alphacoronaviruses use #human CEACAM6 to enter #cells

 

Abstract

Identifying viruses with zoonotic potential on the basis of their ability to enter human cells is a critical component of pandemic prediction, prevention and preparedness. Here using a computational approach that retains maximum phylogenetic diversity, we selected an optimal subset of alphacoronavirus spike proteins to screen against broad coronavirus receptor libraries. Most of the selected spike proteins did not use any of the established coronavirus receptors. However, the pseudotyped spike protein of Cardioderma cor (heart-nosed bat) coronavirus KY43 (CcCoV-KY43) could enter human cells. Using a recombinant CcCoV receptor-binding domain (RBD) and a human receptor screening platform, we identified direct interactions with the human CEACAM proteins CEACAM3, CEACAM5 and CEACAM6. Overexpression of human CEACAM6—a protein widely expressed in the human lung—conferred permissivity to otherwise refractory human cells. A crystal structure showed that the RBD binds the amino-terminal IgV-like domain of human CEACAM6. Immune surveillance studies using sera of individuals from the Taveta region of Kenya, where CcCoV-KY43 was identified, did not show significant evidence of recent spillover. Wider characterization of alphacoronaviruses related to CcCoV-KY43 showed that human CEACAM6 is used by two other CcCoVs collected in Kenya. Moreover, there was more restricted nonhuman CEACAM6 tropism for viruses isolated from Rhinolophus bats from Russia and China. Thus, alphacoronaviruses that use CEACAM6 are probably geographically widespread, and viruses from East Africa show potential for transmission to humans.

Source: 

Link: https://www.nature.com/articles/s41586-026-10394-x

____

Decade-long #warming accelerates #antibiotic #resistance in #grassland soils

 

Abstract

Soils are critical reservoirs of antibiotic-resistance genes (ARGs), which are strongly shaped by microbial interactions and environmental conditions and are therefore highly sensitive to disturbance. Although climate warming is recognized as one of the most significant disturbances to microbial communities and their functions, its impacts on soil resistomes remain poorly understood. Here we investigated the effects of decade-long experimental warming on ARGs in grassland soils using integrated experimental and computational approaches. Our results revealed that ARG abundance substantially increased (23.9%) under warming—particularly glycopeptide- and rifamycin-resistance genes. Warming specifically enriched Actinomycetota hosts, including various potential plant pathogens, and enhanced ARG mobility. Large-scale unprecedented isolates-based phenotypic analyses also validated that warming increased bacterial resistance to multiple antibiotics. Further mechanistic analyses revealed that warming increased ARG abundance primarily through co-selection of resistance genes physically linked to adaptive traits (for example, thermal tolerance and nitrogen assimilation) and positive selection for thermal tolerance genes, which could be further amplified via horizontal gene transfer. Together, these findings convincingly demonstrate that climate warming substantially accelerates soil antibiotic resistance at genomic, ecological and evolutionary levels, with broad implications for public health and environmental sustainability in a warming world.

Source: 

Link: https://www.nature.com/articles/s41586-026-10413-x

____

#Ensitrelvir for the #treatment of hospitalized adults with #COVID19: an international phase 3 randomized placebo-controlled trial

 

Abstract

Background

Antivirals remain an important treatment strategy for persons who experience severe and life-threatening COVID-19. Ensitrelvir is an oral 3CL protease inhibitor with potent antiviral activity.

Methods

We conducted an international randomized, placebo-controlled trial of ensitrelvir with standard of care (SOC) among adults hospitalized for COVID-19. The primary outcome was clinical recovery assessed by the Days to Recovery Scale through Day 60 (DRS-60), analyzed using a Van Elteren test.

Results

From 2023 to 2025, 589 participants received blinded study treatment (293 ensitrelvir and 296 placebo). Median age was 69 years, 49% were female, 68% were White, and SOC commonly included corticosteroids (61% and 54%) and remdesivir (62% and 60%) in ensitrelvir and placebo groups, respectively. Median DRS-60 category was 6 (IQR: 3-15) in the ensitrelvir and 5.5 (IQR: 3-12) in the placebo group (p=0.19), and the OR was 0.82 (95% CI: 0.62-1.09) for a better DRS-60 category with ensitrelvir. Ensitrelvir participants had lower detectable viral antigen in plasma at Day 5 (13.4% vs 25.1%; p<0.001). There was no difference in secondary clinical outcomes or pre-specified safety outcomes, though the mortality rate was 6.1% vs 4.4% and the frequency of hemorrhagic events was 3.4% vs 0.3% among ensitrelvir and placebo groups, respectively.

Conclusions

Ensitrelvir treatment did not improve clinical recovery in addition to SOC for adults hospitalized for COVID-19. The lower illness severity in the Omicron era compared to earlier periods in the COVID-19 pandemic, and high use of remdesivir and corticosteroids, may have contributed to the lack of clinical benefit.

Source: 

Link: https://academic.oup.com/cid/advance-article-abstract/doi/10.1093/cid/ciag272/8660678?redirectedFrom=fulltext

____

Next-Generation #Sequencing #Strategies During the 2024–2025 Avian #Influenza #H5N1 #Emergency Response in the #US

 

Abstract

The first influenza A(H5N1) human case associated with the A(H5N1) dairy cattle outbreak in the United States was identified in April 2024. The U.S. CDC response to this outbreak was activated days later and remained active until July 2025. During this time, 70 human cases of influenza A(H5N1) were detected with a range of epidemiological links to sources of exposure. Next-generation sequencing (NGS) of human samples was an effectual mechanism for tracking and analyzing the outbreak evolution throughout the response. Due to the specimens’ importance and their variable physical quality, an assortment of laboratory methods was utilized including influenza segment-specific amplification, enrichment capture, short-read, and long-read sequencing. Combining these methods allowed for high-quality genomic data production with rapid turnaround times—typically 2 days from sample receipt to public database submission. By leveraging replicate sequencing, enrichment capture, and sequencing of diagnostic amplicons, valuable genomic data could be produced directly from human clinical specimens that would have normally been considered too weak for routine virologic surveillance sequencing. The resulting assemblies were characterized and analyzed by CDC and shared with local and state public health authorities to facilitate case investigations and risk assessment. These data were further used for phylogenetic analyses of viruses from human cases to investigate likely animal-to-human transmission events and identify clusters within the outbreak that might indicate trends in the types of exposures. Through the adaptable laboratory workflow and the rapid release of viral genomic data, the public health risk mitigation strategies could be evaluated and adjusted in real time.

Source: 

Link: https://www.mdpi.com/1999-4915/18/4/482

____

Dual-route #H5N1 #vaccination induces systemic and mucosal #immunity in murine and bovine #models

 

Abstract

Highly pathogenic H5N1 avian influenza (clade 2.3.4.4b) has spread widely among dairy cattle herds since early 2024, causing major economic losses. This zoonotic event emphasizes the urgent need for H5 vaccines eliciting strong, durable, cross-reactive immune responses in cows. To address this, we immunized mice and cattle with a centralized consensus H5 vaccine, localizing near the central node of the human H5 phylogenetic tree. The vaccine was delivered using serotype-switched adenoviral vectors in a prime–boost regimen, combined with intramuscular and intranasal coadministration to target systemic and mucosal immunity and elicit strong humoral and cellular immune responses. This approach strategically integrates multiple innovative features: centralized consensus immunogens, mucosal targeting, and vector serotype switching aimed at maximizing immune protection against H5N1 viruses. Our results show that vaccination elicits strong humoral and cellular immunity in both mice and calves. In challenge experiments, vaccinated mice were fully protected against lethal infection with divergent H5N1 strains, including A/bovine/Ohio/B24OSU-439/2024. Vaccine-induced immunity was consistent across species, supporting the translatability of the mouse model findings to cattle. Overall, our findings represent a promising approach for immunizing key livestock, including cattle, against highly pathogenic avian influenza H5N1, mitigating agricultural losses, and reducing the risk of zoonotic transmission.

Source: 

Link: https://www.nature.com/articles/s41541-026-01460-6

____

Timing of #Remdesivir Initiation and Clinical #Outcomes in Hospitalized Patients with #COVID19 Who Are at High Risk of Disease Progression in #Japan: A Health Insurance Claims Database Study

 

Abstract

Early initiation of remdesivir (RDV) is recommended to improve COVID-19 outcomes, but real-world studies describing patterns of RDV use and related outcomes among Japanese COVID-19 patients at high-risk of severe outcomes or death are limited. This claims-based cohort study included 60,165 high-risk patients hospitalized with COVID-19 between October 2021 and June 2023 using the DeSC Healthcare claims database. Patients were categorized into early-RDV (within 2 days of hospital admission), late-RDV (between day 3 and day 7), and no-RDV groups based on RDV initiation timing. Descriptive analyses were performed according to RDV groups. Of the study patients, ≥85% were very elderly (≥75 years). Approximately 39% of patients received early RDV, 2% received late RDV, and 59% received no RDV. By day 28, the proportion of alive discharge for early-, late-, and no-RDV groups was 74.9%, 63.1%, and 71.8%, respectively. The mortality for early-, late-, and no-RDV groups was 7.7%, 8.8%, and 8.4%, respectively. Future hypothesis-driven studies with an appropriate adjustment for confounders are needed to formally evaluate the impact of RDV initiation timing on clinical outcomes in this high-risk, predominantly late-elderly population in Japan.

Source: 

Link: https://www.mdpi.com/1999-4915/18/4/479

____

Emergence of D1.1 #reassortant #H5N1 avian #influenza viruses in North #America

 

Abstract

Since 2021, highly pathogenic avian influenza viruses (HPAIVs) belonging to H5N1 clade 2.3.4.4b have circulated widely in North American wild birds and repeatedly spilled over into mammals. In 2025, the first H5N1-associated deaths in humans were recorded in the Western hemisphere, raising questions about how the ongoing evolution of the virus in wild birds impacts spillover risk. Here, our analysis of 21,471 H5N1 genomes identified an evolutionary shift in mid-2024, driven by interhemispheric migration from Asia and reassortment with new antigens. The genotypes that dominated the early years of North America's H5N1 epizootic traced their ancestry back to Europe, but Asia was the source of new "D1.1" genotype viruses that (a) spread faster, (b) have higher reassortment potential, (c) a broader host range, (d) repeatedly spill over to bovines, and (e) cause severe disease in humans, including non-farm workers.

Competing Interest Statement

The authors have declared no competing interest.

Funder Information Declared

Research Foundation - Flanders, https://ror.org/03qtxy027, G098321N, G0E1420N

European Union Horizon 2023 RIA project LEAPS, 101094685

DURABLE EU4Health project 02/2023-01/2027, 101102733

Fonds National de la Recherche Scientifique, F.4515.22

European Union Horizon 2020 project MOOD, 874850

Centers of Excellence for Influenza Research and Response, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Department of Health and Human Services, 75N93021C00014

Source: 

Link: https://www.biorxiv.org/content/10.64898/2025.12.19.695329v2

____

#Outdoor roaming of owned #cats elevates #risk of zoonotic #pathogen #exposure: A global synthesis

 

Abstract

Domestic animals play a central role in pathogen transmission at the human–wildlife interface. Domestic cats, in particular, are uniquely consequential in disease spillover dynamics due to their global distribution, large, human-subsidized free-roaming populations, and high contact rate with humans, domestic animals, and wildlife. However, the extent to which human ownership and management mitigate this spillover risk remains a key knowledge gap. To address this gap, we conducted a global systematic review and quantitative synthesis of the prevalence and diversity of zoonotic pathogens in indoor-only, outdoor-owned (roaming unsupervised), and unowned (feral or stray) cats. Our dataset comprised 174,064 individuals from 88 countries, representing 124 pathogen species, 97 of which are zoonotic. Using generalized linear models within a Bayesian framework and rarefaction analyses, we show that ownership provides limited protection against zoonoses when owned cats have unsupervised outdoor access. Outdoor-owned cats were 3–5 times more likely to carry zoonotic pathogens than indoor-only cats, and, notably, had infection odds statistically equivalent to those of feral cats, despite receiving presumed veterinary care and feeding. Feral cats carried the highest pathogen diversity, however, outdoor-owned cats still harbour 1.5 times the helminth richness of indoor cats, highlighting their potential as effective bridges for pathogen spillover. With approximately 62% of owned cats roaming freely worldwide, and rates exceeding 90% in some regions, these findings reveal a major yet overlooked route of zoonotic risk. Public health and One Health frameworks have traditionally focused on feral cats; however, our results highlight the need to explicitly incorporate owned outdoor cats into zoonotic disease prevention strategies by restricting unsupervised roaming and promoting responsible ownership practices. Without such integration, current frameworks risk overlooking a pervasive and preventable pathway for pathogen transmission at the human–wildlife–domestic animal interface.

Source: 

Link: https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014160

____