A live attenuated NS1-deficient #vaccine candidate for #cattle-origin #influenza #H5N1 clade 2.3.4.4.b viruses

Abstract

Avian Influenza viruses (AIVs) present a public health risk, especially with seasonal vaccines offering limited protection. AIV H5N1 clade 2.3.4.4b has caused a multi-state outbreaks in the United States (US) poultry and cattle since March 2024, raising pandemic concerns. We developed a nonstructural protein 1 (NS1)-deficient mutant of a low pathogenic version of the cattle-origin human influenza A/Texas/37/2024 H5N1, namely LPhTXdNS1, and assessed its safety, immunogenicity, and protection efficacy. LPhTXdNS1 is attenuated in vitro, showing reduced replication efficiency in Vero cells and inability to control IFNβ promoter activation. The LPhTXdNS1-immunized C57BL/6 J mice exhibit significantly reduced viral replication and pathogenicity compared to those infected with the low pathogenic version expressing NS1, namely LPhTX. Notably, a single intranasal dose of LPhTXdNS1 elicited protective immune responses, providing robust protection against lethal wild-type H5N1 challenge. These results demonstrate that LPhTXdNS1 is safe and able to induce protective immune responses against H5N1.

Source: npj Vaccines, https://www.nature.com/articles/s41541-025-01207-9

____

History of Mass Transportation: the FS D341 Diesel-Electric Locomotive

 

Di Bruno Cividini - https://www.ilportaledeitreni.it/2018/06/07/d-341-1025-san-candido-febbraio-1975/, Pubblico dominio, https://commons.wikimedia.org/w/index.php?curid=78316787

Source: Wikipedia, https://it.wikipedia.org/wiki/Locomotiva_FS_D.341#/media/File:FS_D.341.1025-2.1975-S.Candido.jpg

____

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Considerations for use of avian #influenza #H5 #vaccines during the #interpandemic and emergence periods

Report of a WHO virtual scientific consultation, September 2024

© World Health Organization 2025 Some rights reserved. This work is available under the Creative Commons AttributionNonCommercial-ShareAlike 3.0 IGO licence (CC BY-NC-SA 3.0 IGO; https://creativecommons.org/licenses/by-nc-sa/3.0/igo).  

Executive summary 

Avian influenza viruses – particularly A(H5) – pose a significant risk for potential pandemics as they can infect humans and other mammals. 

The high mutation rate of influenza viruses raises concerns about their potential to adapt for efficient human-to-human transmission. 

Influenza vaccines are crucial tools in mitigating the impact of influenza epidemics and pandemics. 

Given the global circulation of A(H5) viruses – especially the spillover to dairy cattle since early 2024 – and the rapidly evolving vaccine landscape, the World Health Organization (WHO) held a virtual scientific consultation on 12–13 September 2024 to review: 

-- the current global A(H5) epidemiological situation; 

-- the availability and landscape of A(H5) vaccines and their characteristics; 

-- updated evidence on A(H5) vaccine immunogenicity, safety and other characteristics; 

and 

-- considerations for the use of A(H5) vaccines, based on expert opinions. 

The consultation did not discuss: 

-- A(H5) vaccine stockpiles; 

-- A(H5) vaccine regulatory approvals or access issues; 

-- mathematical modelling to inform options for use of A(H5) vaccines in the context of other public health measures and stockpiles; 

-- acceptance, cost, cost–effectiveness, risk–benefit ratios or other programmatic considerations; 

or 

-- strategies for animal A(H5) vaccination. 

Topics such as equity were also not discussed, as the Pandemic Influenza Preparedness Framework has enabled WHO to make significant progress in preparing for equitable access to vaccines. 

The primary objective of the virtual scientific consultation was to update WHO’s Options for the use of human H5N1 influenza vaccines and the WHO H5N1 vaccine stockpile, which was developed during a previous scientific consultation on A(H5N1) held in October 2007. 

The participants in the 2024 consultation included: 

-- experts from research academia, WHO collaborating centres and essential regulatory laboratories of the Global Influenza Surveillance and Response System, 

-- experts from countries, 

-- the WHO Strategic Advisory Group of Experts (SAGE) Secretariat, 

-- industry associations and other partners. 

This report summarizes the outcomes of the virtual scientific consultation, and is expected to be used during the potential update of SAGE recommendations on the use of licensed H5N1 vaccines. 

The A(H5) vaccine landscape included in this report is up to date as of 31 March 2025. 

A(H5) viruses pose a threat to human and animal health globally. National, regional and global preparedness is needed urgently. 

Countries should remain vigilant in conducting surveillance for emerging influenza viruses with pandemic potential. 

WHO will continue to monitor the situation and provide updated risk assessments, guidance and technical support, where needed. 

(...)

Source: World Health Organization, https://www.who.int/publications/i/item/9789240111462

____

#Mpox Multi-country, external #situation #report no. 55 published 11 July 2025 (#WHO, Summary)

 

Highlights

• All clades of monkeypox virus (MPXV) continue to circulate in several countries. When mpox outbreaks are not rapidly contained and human-to-human transmission is not interrupted, they continue to pose a risk of sustained community transmission.  

• Since the last edition of this report, no new countries have reported cases of clade Ib MPXV for the first time.  

• Nineteen countries in Africa have reported ongoing mpox transmission in the past six weeks. Clade IIb MPXV continues to be reported in West Africa, while Central African countries report both clade Ia and clade Ib MPXV, and East African countries report clade Ib MPXV. 

• The recent overall downward trend of confirmed cases across the continent is driven by the decrease in cases in Sierra Leone, the Democratic Republic of the Congo, and some reporting delays. Challenges with access to testing continue in the Democratic Republic of the Congo.  

• An upward trend has been observed in West Africa, particularly in Guinea, Liberia, and Togo, where growing outbreaks of clade IIb MPXV have been reported in recent weeks. This report contains a summary of the epidemiological situation in these three countries.  

• China has reported nine additional cases of mpox due to clade Ib MPXV since the last situation report. Epidemiological investigations for some of them are ongoing, and the transmission status of clade Ib MPXV in China is classified as "Unknown" pending further information. 

• Türkiye has retrospectively notified WHO of a case of mpox due to clade Ia MPXV, detected in October 2024 in a traveler from the Democratic Republic of the Congo. No secondary cases were reported among the contacts of the case who underwent monitoring.  

• This report includes a summary of the fourth meeting of the International Health Regulations (2005) Emergency Committee regarding the upsurge of mpox, held on 5 June 2025. 

(...)

Source: World Health Organization, https://www.who.int/publications/m/item/multi-country-outbreak-of-mpox--external-situation-report--55---11-july-2025

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#USA, #Wastewater Data for Avian #Influenza #H5 (US #CDC, July 11 '25)

 

{Excerpt}

Time Period: June 29, 2025 - July 05, 2025

-- H5 Detection: 2 sites (0.6%)

-- No Detection: 330 sites (99.4%)

-- No samples in last week: 77 sites

(...)

Source: US Centers for Disease Control and Prevention, https://www.cdc.gov/nwss/rv/wwd-h5.html

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The mutational landscape of #SARS-CoV-2 provides new insight into viral #evolution and #fitness

Abstract

Although vaccines and treatments have strengthened our ability to combat the COVID-19 pandemic, new variants of SARS-CoV-2 continue to emerge in human populations. Because the evolution of SARS-CoV-2 is driven by mutation, a better understanding of its mutation rate and spectrum could improve our ability to forecast the trajectory of the pandemic. Here, we use circular RNA consensus sequencing (CirSeq) to determine the mutation rate of six SARS-CoV-2 variants and perform a short-term evolution experiment to determine the impact of these mutations on viral fitness. Our analyses indicate that the SARS-CoV-2 genome mutates at a rate of ∼1.5 × 10−6/base per viral passage and that the spectrum is dominated by C → U transitions. Moreover, we find that the mutation rate is significantly reduced in regions that form base-pairing interactions and that mutations that affect these secondary structures are especially harmful to viral fitness. In this work, we show that the biased mutation spectrum of SARS-CoV-2 is likely a result of frequent cytidine deamination and that the secondary structure of the virus plays an important role in this process, providing new insight into the parameters that guide viral evolution and highlighting fundamental weaknesses of the virus that may be exploited for therapeutic purposes.

Source: Nature Communications, https://www.nature.com/articles/s41467-025-61555-x

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Isolation, characterization and phylogenetic analyses of avian #influenza A #H9N2 viruses isolated from #poultry between 2019 and 2023 in #Egypt

Abstract

The current study aimed to investigate the genetic characterization and evolution of low pathogenic avian influenza virus H9N2 in Egypt. Ten H9N2 viruses were recently isolated from samples collected between 2019 and 2023. Phylogenetic analysis of the haemagglutinin (HA) gene segment of the H9N2 isolates showed a relatedness with G1 H9 4.2 lineage and clustered within genotype III of the Egyptian strains identified earlier in 2018. The majority of H9N2 strains had seven and eight glycosylation sites in HA and neuraminidase (NA) respectively. All strains carried H191 and L234 residues in their hemagglutinin which are markers facilitating avian-to-human cross species barrier transmission. No stalk deletions were detected in NA gene. In addition, genetic analysis of the NA and M encoding proteins revealed the absence of substitutions associated with resistance to oseltamivir and amantadine. The NA showed S372A and R403W substitutions which were previously detected in H3N2 and H1N2 viruses that were reported in previous influenza pandemics in 1975 and 2001 respectively. Many mutations associated with virulence and mammalian infection were detected in internal proteins such as PB2(V504), PB1-F2(N66), PA (V127, L672, and L550), M2(S64), and NS1(42S). Analysis showed the presence of full-length PB1-F2 with 227PDZ230 motif which is associated with virus virulence and pathogenesis. Mammalian associated mutations such as PB2 (I 667, T64), PB1-P13, PB1-F2-S82, NP-K214, NP-Q398 and M1-I15 were detected. The HA gene was under positive selection pressure especially at sites 198 and 235 of RBS, while other internal genes were under negative selection pressure. The study highlights the importance of continuous monitoring of H9N2 virus to enable timely implementation of control measures in poultry populations in Egypt.

Source: BMC Veterinary Research, https://bmcvetres.biomedcentral.com/articles/10.1186/s12917-025-04514-4

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Fourth #meeting of #IHR (2005) Emergency #Committee regarding the upsurge of #mpox 2024 (#WHO, July 10 '25)

 

{Summary}

The Director-General of the World Health Organization (WHO) is hereby transmitting the report of the fourth meeting of the International Health Regulations (2005) (IHR) Emergency Committee (Committee) regarding the upsurge of mpox 2024, held on Thursday, 5 June 2025, from 12:00 to 17:00 CEST.

Concurring with the advice unanimously expressed by the Committee during the meeting, the WHO Director-General determined that the upsurge of mpox 2024 continues to meet the criteria of a public health emergency of international concern (PHEIC) and, accordingly, on 9 June 2025, issued temporary recommendations to States Parties, available here.  

The WHO Director-General expresses his most sincere gratitude to the Chair, Members, and Advisors of the Committee.

(...)

Source: World Health Organization, https://www.who.int/news/item/10-07-2025-fourth-meeting-of-the-international-health-regulations-(2005)-emergency-committee-regarding-the-upsurge-of-mpox-2024

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#Portugal - #Influenza A #H5N1 viruses of high pathogenicity (Inf. with) (non-poultry including wild birds) (2017-) - Immediate notification

 

By Alexis Lours - Own work, CC BY 4.0, https://commons.wikimedia.org/w/index.php?curid=138694692

___

A Yellow-legged Gull in Leiria Region.

Source: WOAH, https://wahis.woah.org/#/in-review/6609

____

A #nanobody-based #therapeutic targeting #Nipah virus limits viral escape

Abstract

Nipah virus (NiV) and Hendra virus (HeV) are highly pathogenic henipaviruses without approved human vaccines or therapies. Here, we report on a highly potent bispecific therapeutic that combines an anti-fusion glycoprotein nanobody with an anti-receptor-binding glycoprotein (RBP) antibody to deliver a dual-targeting biologic that is resistant to viral escape. We show that the nanobody, DS90, engages a unique, conserved site within the fusion glycoprotein of NiV and HeV and provides neutralization and complete protection from NiV disease. Bispecific engineering of DS90 with the anti-RBP monoclonal antibody m102.4 results in neutralization, elimination of viral escape and superior protection from NiV disease compared to leading monovalent approaches. These findings carry implications for the development of cross-neutralizing immunotherapies that limit the emergence of henipaviral escape mutants.

Source: Nature Structural and Molecular Biology, https://www.nature.com/articles/s41594-025-01598-2

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#Genetic Characterization of Highly Pathogenic Avian #Influenza #H5N1 Clade 2.3.4.4b, #Antarctica, 2024

Abstract

In 2024, we sequenced highly pathogenic avian influenza virus A(H5N1) clade 2.3.4.4b genomes isolated from 5 brown skuas from James Ross Island, Antarctica. Phylogenetic analysis suggested the virus reached Antarctica through South America. Continued genetic surveillance will be critical to elucidate H5N1 virus transmission dynamics within Antarctica and surrounding areas.

Source: US Centers for Disease Control and Prevention, https://wwwnc.cdc.gov/eid/article/31/8/25-0186_article

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#Transmission Dynamics of Highly Pathogenic Avian #Influenza #H5N1 and #H5N6 Viruses in Wild #Birds, South #Korea, 2023–2024

Abstract

We analyzed 15 cases of highly pathogenic avian influenza (HPAI) clade 2.3.4.4b virus infections detected in wild birds in South Korea during September 2023–March 2024. We isolated and sequenced 8 H5N1 and 7 H5N6 viruses. We investigated spatiotemporal transmission dynamics by using a Bayesian discrete trait phylodynamic model that incorporated geographic and host species information. Our source–sink dynamics support introductions of H5N1 viruses from northern Japan to South Korea and subsequent spread through multiple regions in South Korea. The H5N6 viruses were most likely introduced into southwestern South Korea and spread northeastward. Wild waterfowl, especially wild ducks, played a key role in transmission of both H5N1 and H5N6 viruses. Our data showed multiple introductions and extensive spread of HPAI clade 2.3.4.4b viruses and bidirectional transmission between Japan and South Korea. Our results highlight the value of enhanced active surveillance for monitoring HPAI viruses, which can provide insight into preventing future outbreaks.

Source: US Centers for Disease Control and Prevention, https://wwwnc.cdc.gov/eid/article/31/8/25-0373_article

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Susceptibility and shedding in Mx1+ and Mx1− female #mice experimentally infected with dairy #cattle #H5N1 #influenza viruses

Summary

Background

Clade 2.3.4.4b highly pathogenic avian influenza A(H5N1) (HPAI H5N1) viruses have spread prolifically in dairy cattle in the US, resulting in dozens of human infections, some without well-established links to animal contacts. Many wild mammals have also been affected, including peridomestic house mice.

Methods

Here, we evaluated susceptibility, tissue tropism, and shedding in female PWK/PhJ and BALB/cJ mice, two laboratory strains derived from house mice that differ in expression of the antiviral restriction factor Mx1. PWK/PhJ mice, which were selected for their natural expression of Mx1, better reflect the antiviral capacity of most wild house mice, whereas BALB/cJ mice lack functional Mx1.

Findings

We found that, regardless of Mx1 expression status, mice are susceptible to infection by dairy cattle HPAI H5N1 viruses, that infection leads to systemic spread to non-respiratory sites, and that infected animals shed virus into the environment via urine. Shed virus remained infectious in urine for at least 24 h at room temperature.

Interpretation

These findings suggest that wild house mice could contribute to HPAI H5N1 environmental contamination and may play a role in transmission to other hosts.

Funding

This work was supported by the National Institute of Allergy and Infectious Diseases Centers of Excellence for Influenza Research and Response (contract 75N93021C00014) and by grants from the Japan Agency for Medical Research and Development (JP25wm0125002, JP253fa627001, and JP24fk0108626, to Y.K.).

Source: EBioMedicine, https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(25)00286-5/fulltext

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Spatiotemporal #reconstruction of the North #American #H5N1 #outbreak reveals successive #lineage #replacements by descendant reassortants

Abstract

The November 2021 introduction of highly pathogenic avian influenza A(H5N1) clade 2.3.4.4b into North America triggered a devastating outbreak, affecting more than 180 million domestic birds and spreading to more than 80 wildlife species across Canada and the US. From this outbreak, we have sequenced 2955 complete A(H5N1) viral genomes from samples collected in Canada and, in conjunction with previously published data, performed multifaceted phylodynamic analyses. These analyses reveal extensive diversification of A(H5N1) viruses via reassortment with low-pathogenic avian influenza viruses. We find evidence of repeated ancestral strain replacement by direct descendants, indicative of compounding viral fitness increases. Spatiotemporal modeling identified critical geographic areas facilitating transcontinental spread and demonstrated genotype-specific host dynamics, offering essential data for ongoing control and prevention strategies.

Source: Science Advances, https://www.science.org/doi/10.1126/sciadv.adu4909

____

#Wastewater #Parvovirus B19 #Signal Amid Rising #Maternal Cases

Abstract

We report widespread detection of parvovirus B19 in Texas Wastewater using hybrid-capture virome sequencing across 43 sites. Wastewater signal correlated with clinical cases at institutional, county, and state levels and preceded case surges by one month. Full-genome coverage enabled real-time mutation tracking, highlighting wastewater's utility for epidemiologic surveillance.

Source: MedRxIV, https://www.medrxiv.org/content/10.1101/2025.07.07.25331044v1

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Adjuvanted #influenza #vaccination increases pre-existing #H5N1 cross-reactive #antibodies and overcomes immune imprinting patterns

Abstract

Highly pathogenic H5N1 avian influenza viruses of clade 2.3.4.4b cause sporadic human infections and currently raise concerns about a new influenza pandemic. Heterogeneities in disease severity and outcome have been observed in the past and are currently reported among infected farm workers in the US. These may be attributed to differences in pre-existing H5N1 cross-reactive antibodies. In this study, we characterize H5N1 cross-reactive antibody landscapes in the current population and assess the effect of pH1N1/AS03 and non-adjuvanted seasonal influenza vaccination on H5N1 cross-neutralizing and IgG antibody titers targeting a range of influenza virus-derived antigens. We were able to detect H5N1 cross-neutralizing antibodies using a VSV-based pseudovirus system that correlated well with antibodies inhibiting the spread of authentic H5N1 viruses. Additionally, we found that pH1N1/AS03 vaccination increases H5N1 cross-reactive antibodies significantly, while non-adjuvanted influenza vaccination only had a marginal effect. Furthermore, we could show that immune imprinting causes distinct H5N1 cross-reactive antibody patterns pre-vaccination, that were erased by pH1N1/AS03 vaccination.

Competing Interest Statement

B.M. has received research support from Moderna and consulting fees from Rocketvax AG. A.D. is a member of scientific advisory boards for Bioaster and Sanofi, is a consultant for Boost Biopharma, Botanical solutions and Vaccine Formulation Institute, and has research collaborations with Moderna, GSK and Sanofi. The remaining authors declare that they have no competing interests.

Funding Statement

This project was supported by the Swiss National Science Foundation Ambizione program (grant number: 193475) and a research grant from Moderna Inc. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Source: MedRxIV, https://www.medrxiv.org/content/10.1101/2025.07.08.25331087v1

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Pathogenicity, #transmissibility, and #receptor #binding of a #human-isolated #influenza A #H10N5 virus

ABSTRACT

Recently, human infections with H10 influenza viruses, including H10N8 and H10N3, have been reported. In January 2024, a case of H10N5 and H3N2 co-infection was reported in Zhejiang Province, China, which is the first human infection with H10N5 avian influenza virus (AIV) globally. Almost simultaneously, we isolated a wild bird-derived H10N5 strain similar to the human H10N5 strain. To assess the public health risk, it is necessary to understand the zoonotic characteristics of these novel H10N5 viruses. Here, we evaluated the biological characteristics of human H10N5, wild bird H10N5, as well as poultry H10N8 in vitro and in vivo. We demonstrate that the novel H10N5 isolates infected and replicated effectively in human lung epithelial cells. They infected BALB/c mice without adaptation, which exhibited robust pathogenicity and caused mouse death. In guinea pig transmission experiments, the H10N5 strain spread through neither direct contact nor airborne exposure, whereas H10N8 transmitted effectively. Additionally, H10N5 exhibited dual receptor-binding characteristics with a stronger preference for avian receptors. The current public health risk of H10N5 is low. However, the occasional spillover infections of H10 AIV into humans and dual receptor-binding characteristics suggest a potential risk of cross-species transmission.

IMPORTANCE

In 2024, the H10N5 AIV was first reported to infect humans. Concurrently, we isolated a strain of H10N5 from wild birds that was highly similar to the human H10N5 strain. However, the zoonotic potential and the associated public health risks of the H10N5 virus remain unclear. In this study, we systematically evaluated the replication characteristics of human H10N5, wild bird H10N5, and poultry H10N8 in human lung epithelial cells, the virulence in mice, the transmission capabilities in guinea pigs, and the receptor-binding properties. Our results demonstrate that these novel H10N5 viruses have not yet acquired the ability to transmit in guinea pigs, but they possess the potential to infect mammals. These findings provide timely insights and warnings for the development of public health prevention strategies.

Source: mBio, https://journals.asm.org/doi/10.1128/mbio.00731-25

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#Phylogenetic analysis of #H5N1 #influenza viruses isolated from dairy #cattle in #Texas in December 2024

LETTER

Highly pathogenic avian influenza (HPAI) viruses of genotype B3.13 were first reported in dairy cattle in March 2024 and, by 4 March 2025, had infected at least 989 cattle herds in 17 states in the US (https://www.aphis.usda.gov/livestock-poultry-disease/avian/avian-influenza/hpai-detections/hpai-confirmed-cases-livestock; accessed on March 24, 2025). Importantly, spillover infections of poultry and mammalian species, including cats and humans, have occurred (https://www.cdc.gov/bird-flu/situation-summary/index.html; accessed on 4 March 2025). Texas reported several infected herds in the spring (1) and early summer of 2024 but saw fewer outbreaks during the second half of 2024, with reported outbreaks in July and December (2). Since September 2024, almost all reported outbreaks of genotype B3.13 viruses in dairy cattle have occurred in California. Here, we characterized self-submitted samples from a farm in Texas that experienced an outbreak in December 2024. This farm had purchased dairy cattle from several states in the US. We, therefore, asked whether the December 2024 outbreak in Texas was caused by B3.13 viruses that circulated undetected in dairy cattle or other species in Texas or resulted from the introduction of B3.13 viruses from California (having the highest number of affected farms at that time) or other states.

(...)

Source: Journal of Virology, https://journals.asm.org/doi/full/10.1128/jvi.00580-25?af=R

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Differential #severity of #SARS-CoV-2 #variant infections in #children and #adults with #COVID19

Highlights

• This study evaluated differences in SARS-CoV-2 variant severity from 2020-2023

• SARS-CoV-2 whole-genome sequencing from 6,916 respiratory swabs was performed

• Four conserved kmer sequences associated with severity were identified

• Infections from the Delta variant had highest likelihood of severe infection

• Omicron BA.4/5 variant was more severe than BA.1 in children, vice-versa in adults

Abstract

We performed virus whole-genome sequencing of 6,916 upper respiratory swabs from adults and children from March 2020 through May 2023 and collected clinical metadata to assess differences in SARS-CoV-2 variant severity and symptomatology. Multivariable logistic regression showed a severity peak with Delta, which had the highest likelihood of severe infection. In children, another peak was observed with BA.4/BA.5, which was associated with more severe infection than both prior (BA.1) and later (BQ.1, BF.7, and XBB) Omicron variants. In contrast, BA.4/BA.5 in adults was associated with less severe infection than BA.1. Genome-wide association studies revealed that nonstructural protein 5 (nsp5, also called 3C-chymotrypsin-like protease), the Paxlovid target, and the spike N-terminal domain were strongly associated with severity. Kmers (contiguous nucleotide sequences of a fixed length k) from these regions matched the prototype Wuhan sequence exactly, corroborating decreases in severity over time. One kmer in the spike gene region was conserved in Delta genomes, with the kmer retained in higher proportions in patients with more severe infection. Our results show, with the exception of Delta, decreased severity associated with SARS-CoV-2 variant infection over time and underscore the potential utility of kmer monitoring to assess variant severity.

Source: Journal of Clinical Virology, https://www.sciencedirect.com/science/article/abs/pii/S1386653225000757?dgcid=rss_sd_all

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Enhancing the #response to avian #influenza in the #US and globally

Summary

The recent emergence of highly pathogenic H5N1 avian influenza virus infections in dairy cows and humans in the U.S. has raised alarms regarding the potential for a pandemic. Over 995 dairy cow herds and at least 70 humans have been affected, including cases of severe disease and the first reported H5N1-related death in the U.S. Sporadic human infections with no known contact with infected animals highlight the possibility of viral adaptation for efficient human-to-human transmission. Concurrently, the virus continues to circulate in wild birds, backyard flocks, and hunted migratory species, further amplifying the risk to humans and domestic animals. This article provides an overview of the current outbreak status, emphasizes the importance of robust surveillance systems to detect emerging strains with pandemic potential, and highlights risks to the U.S. dairy and poultry industries. Recommendations for risk mitigation include enhanced biosecurity measures, improved surveillance, decentralized testing, and targeted public health messaging. The Global Virus Network calls for urgent, proactive measures to prevent widespread outbreaks, leveraging lessons learned from prior pandemics. These measures include targeted vaccination, improved communication strategies to combat vaccine hesitancy, and the incorporation of social sciences to address barriers to public health interventions.

Source: Lancet Regional Health Americas, https://www.thelancet.com/journals/lanam/article/PIIS2667-193X(25)00110-3/fulltext

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Efficacy, immunogenicity, and safety of a next-generation #mRNA-1283 #COVID19 #vaccine compared with mRNA-1273 vaccine (NextCOVE)...

Summary

Background

mRNA-1283 is an investigational, next-generation COVID-19 vaccine that encodes only the immunodominant regions of the SARS-CoV-2 spike protein—the receptor-binding domain (RBD) and the N-terminal domain rather than the full-length spike used in currently authorised mRNA vaccines. We evaluated the relative vaccine efficacy (rVE), immunogenicity, and safety of mRNA-1283 compared to the first-generation vaccine (mRNA-1273).

Methods

This randomised, observer-masked, active-controlled, phase 3 trial (NextCOVE) was conducted in individuals (aged ≥12 years) with no evidence of SARS-CoV-2 infection within 90 days of screening in the USA, the UK, and Canada. Participants were randomly assigned in a 1:1 ratio to receive one 10 μg dose of the bivalent formulation of mRNA-1283 (original plus omicron BA.4/BA.5) or 50 μg of the bivalent mRNA-1273, encoding the same variants. Randomisation was stratified by age (12–17 years, 18–64 years, and ≥65 years). Primary objectives comparing mRNA-1283 with mRNA-1273 were non-inferior rVE to prevent a first event of COVID-19 from 14 days after study injection to the end of follow-up (assessed in the per-protocol set for efficacy, with non-inferiority declared when the lower bound of the α-adjusted two-sided CI for rVE was greater than –10%), non-inferior immunogenicity at day 29 (assessed in the per-protocol immunogenicity subset, with non-inferiority declared when the lower bounds of the CIs for the geometric mean concentration ratios [GMRs] of neutralising antibodies against SARS-CoV-2 D614G and omicron BA.4/BA.5 were >0·667 and the lower bounds of the 95% CI seroresponse rate differences for the two variants were greater than –10%), and safety (assessed in the safety set, which included all participants who received a vaccination). The trial is registered at ClinicalTrials.gov (NCT05815498) and is complete.

Findings

Between March 28 and Aug 23, 2023, we screened 13 054 individuals for eligibility and randomly allocated 11 454 participants (5728 to mRNA-1283 and 5726 to mRNA-1273). 1177 confirmed COVID-19 events occurred up to Jan 31, 2024 (560 [9·9%] of 5679 in mRNA1283.222 and 617 [10·8%] of 5687 in mRNA-1273.222). The median age of participants at enrolment was 56 years (IQR 38–66). Of the 11 417 participants who received a vaccine, 6200 (54·3%) were female and 5217 (45·7%) were male; 9381 (82·2%) were White; and 1510 (13·2%) were Hispanic or Latino. Of the total cohort, 992 (8·7%) participants were aged 12–17 years, 7151 (62·6%) were aged 18–64 years, and 3274 (28·7%) were 65 years and older; in addition, 6857 participants (60·1%) were 50 years and older. The rVE point estimate was 9·3% (99·4% CI –6·6 to 22·8; p=0·0005). The GMR was 1·3 (95% CI 1·2 to 1·5) for BA.4/BA.5 and 1·2 (1·1 to 1·4) for D614G. The day-29 seroresponse rate difference was 14·4% (95% CI 9·3 to 19·4) for BA.4/BA.5 and 10·7% (6·0 to 15·4) for D614G. Local and systemic adverse reactions were similar between mRNA-1283 and mRNA-1273; mRNA-1283 was associated with fewer injection-site pain reactions than mRNA-1273 (3905 [68·5%] of 5701 vs 4419 [77·5%] of 5705, respectively). The frequency of unsolicited adverse events, serious adverse events, and medically attended adverse events were similar between groups during the first 28 days after injection. One event of sudden death occurred in a participant with underlying cardiovascular disease in the mRNA-1273 group; it was reported as related to vaccination due to its temporal association.

Interpretation

mRNA-1283 was well-tolerated. The rVE and immunogenicity non-inferiority criteria were met, with higher antibody responses for mRNA-1283 versus mRNA-1273. The potential clinical benefit of mRNA-1283 versus mRNA-1273 needs to be confirmed in post-marketing evaluation.

Funding

Moderna.

Source: The Lancet Infectious Diseases, https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(25)00236-1/fulltext?rss=yes

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Predictive #models of #influenza A virus #lethal disease yield insights from #ferret respiratory tract and #brain tissues

Abstract

Collection of systemic tissues from influenza A virus (IAV)-infected ferrets at a fixed timepoint post-inoculation represents a frequent component of risk assessment activities to assess the capacity of IAV to replicate systemically. However, few studies have evaluated how the frequency and magnitude of IAV replication at discrete tissues contribute to within-host phenotypic outcomes, limiting our ability to fully contextualize results from scheduled necropsy into risk assessment settings. Employing aggregated data from ferrets inoculated with > 100 unique IAV (both human- and avian-origin viruses, spanning H1, H2, H3, H5, H7, and H9 subtypes), we examined relationships between infectious virus detection in four discrete tissue types (nasal turbinate, lung, brain, and olfactory bulb [BnOB]) to clinical outcomes of IAV-inoculated ferrets, and the utility of including these discrete tissue data as features in machine learning (ML) models. We found that addition of viral tissue titer data maintained high performance metrics of a predictive lethality classification ML model with or without inclusion of serially-collected virological and clinical data. Interestingly, infectious virus in BnOB was detected at higher frequency and magnitude among IAV associated with high pathogenicity phenotypes in ferrets, more so than tissues from the respiratory tract; in agreement, BnOB was the highest relative ranked individual tissue specimen in predictive classification models. This study highlights the potential role of BnOB viral titers in assessing IAV pathogenicity in ferrets, and highlights the role ML approaches can contribute towards understanding the predictive benefit of in vivo-generated data in the context of pandemic risk assessment.

Source: Scientific Reports, https://www.nature.com/articles/s41598-025-09154-0

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Vertical #Transmission of #Bovine #H5N1 during #Pregnancy and #Lactation in #Mice

Abstract

Panzootic spillover of H5N1 virus clade 2.3.4.4b has resulted in expanded host range among placental mammals, with lactation transmission via milk documented. Whether infection during pregnancy leads to in utero or lactational vertical transmission remains unknown. Pregnant outbred mice were infected with A/bovine/Ohio/B24OSU-472/2024 during the second or third trimester equivalent. Second trimester infection caused in utero infection, with infectious virus detected in the uterus, placenta, and fetus. Birth following third trimester infection resulted in offspring with decreased size and neurodevelopmental delays, with infectious virus detected in the neonatal milk ring and lungs as well as mammary tissues. Ongoing H5N1 infections present increased risk for human exposure and an H5N1 vertical transmission model in placental mammals is essential for understanding viral spread and evaluating treatments during pregnancy.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.07.07.663583v1

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The #spread of highly pathogenic avian #influenza virus is a #social #network problem

Abstract

Despite identification of Highly Pathogenic Avian Influenza viruses nearly 75 years ago, the transmission pathways among wild animals remain incompletely described. We propose the use of social networks, to complement phylodynamic modeling, for better surveillance, prediction, and prioritization of HPAI.

Source: PLoS Pathogens, https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1013233

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#Wastewater #Data for Avian #Influenza A(#H5) (#US CDC, July 7 '25)

 

{Excerpt}

Time Period: June 22, 2025 - June 28, 2025

-- H5 Detection: 3 sites (0.8%)

-- No Detection: 370 sites (99.2%)

-- No samples in last week: 52 sites

(...)

Source: US Centers for Disease Control and Prevention, https://www.cdc.gov/nwss/rv/wwd-h5.html

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#Finland - #Influenza A #H5N5 viruses of high pathogenicity (Inf. with) (non-poultry including wild birds) (2017-) - Immediate notification

By © Giles Laurent, gileslaurent.com, License CC BY-SA, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=142133890

 A wild Golden Eagle in Lapin aluehallintovirasto Region.

Source: WOAH, https://wahis.woah.org/#/in-review/6597

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

 

By Andreas Trepte - Own work, CC BY-SA 2.5, https://commons.wikimedia.org/w/index.php?curid=10944563

A Great black-backed Gull in Nordland Region.

Source: WOAH, https://wahis.woah.org/#/in-review/6594

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