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Detection of low pre-existing humoral #immunity against #influenza virus #H5N1 clade 2.3.4.4b in unexposed individuals

Abstract The spill-over of Influenza A virus H5N1 clade 2.3.4.4b from cattle to humans highlights the risk of a human H5N1 pandemic . Given the impact of pre-existing immunity on the course and severity of viral infections, we comprehensively assessed the humoral immunity against the H5N1 A/Texas/37/2024 isolate in H5N1- naive individuals . To this end, we performed complementary binding and neutralization assays on 66 subjects and ranked activities among a panel of 76 influenza A virus isolates. We detected low but distinct cross-neutralizing titers against A/Texas/37/2024 with a 3.9 to 15.6-fold reduction compared to selected H1N1 or H3N2 strains. By cloning and evaluating 136 monoclonal antibodies from memory B cells, we identified potent A/Texas/37/2024-neutralizing monoclonal antibodies in five out of six investigated individuals. These antibodies cross-neutralize H1, compete with antibodies targeting the HA stem, and protect mice from lethal H5N1 challenge. Our findings demonstra...

Development of #DNA and #mRNA-LNP #vaccines against an #H5N1 clade 2.3.4.4b #influenza virus

ABSTRACT Effective vaccines are an important public health tool which may be needed to combat the emerging, highly pathogenic H5N1 avian influenza viruses currently circulating in cattle and poultry in the United States . While nucleic acid-based vaccines such as mRNA -lipid nanoparticles (LNPs) have several potential advantages during a viral epidemic compared to traditional seasonal influenza vaccines , their utility and efficacy against H5N1 viruses remain incompletely defined. Here, we developed novel DNA- and mRNA-LNP-based vaccines encoding both hemagglutinin (HA) and neuraminidase (NA) proteins from the human-isolated highly pathogenic avian influenza H5N1 strain, A/Texas/37/2024, in a single open reading frame. This dual-antigen expression approach elicited strong protective immune responses targeting both the HA and NA proteins and provided complete protection against lethal viral challenges in a murine model . The pre-clinical data described in this work suggest that these mu...

Low levels of #H5N1 HA and NA #antibodies in the #human population are boosted by seasonal #H1N1 #infection but not by #H3N2 infection or influenza #vaccination

Abstract An increase in the number of human cases of influenza A/H5N1 infection in the US has raised concerns about the pandemic potential of the virus . Preexisting population immunity is a key determinant for risk assessment and pandemic potential for any virus. Antibody responses against the bovine A/H5N1 hemagglutinin (HA) and neuraminidase (NA) proteins were measured among a population of influenza-vaccinated or influenza-infected individuals . Modest titers of bovine A/H5N1 HA-binding antibodies and low to undetectable neutralizing antibody responses were detected in a cohort of 73 individuals . Conversely, bovine A/H5N1 NA binding and neuraminidase-inhibiting antibody responses were comparable to those against a human A/ H1N1 NA at baseline. Seasonal influenza vaccination failed to significantly increase antibody titers against both HA and NA glycoproteins of bovine A/H5N1. Recent infection with human A/H1N1 but not A/H3N2 viruses induced significant increases in bovine A/H5N1 n...

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

  By Scott Wieman - Own work, CC BY-SA 3.0,  https://commons.wikimedia.org/w/index.php?curid=24620634 A wild Herring Gull in Nordland Region. Source: WOAH,  https://wahis.woah.org/#/in-review/6621 ____

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

Di dierat-stock - Crow-1, CC BY 3.0,  https://commons.wikimedia.org/w/index.php?curid=33155653 A wild Carrion Crow in Khabarovsk Region. Source: WOAH,  https://wahis.woah.org/#/in-review/6622 ____

The #impact of highly pathogenic avian #influenza #H5N1 virus infection on dairy #cows

Abstract Highly pathogenic avian influenza (HPAI) H5N1 virus has been associated with severe mastitis in dairy cows , leading to decreased milk production . Here we investigated the impact of H5N1 virus infection in health and production parameters in an affected dairy herd in Ohio . Clinical disease , which lasted for about three weeks , was recorded in 20.0% (777/3876) of the adult cows. Milk losses of ~900 kg per cow were recorded in affected cows during a 60 day-post-outbreak period . Seroprevalence was 89.4% (570/637) in the herd, with 76.1% (485/637) of seropositive animals being subclinically infected . Clinically affected cows presented an increased risk of death (6 times) and of premature herd removal (3.6 times) when compared to non-clinical cows. Economic losses due to decreased milk production, mortality, and early herd removal were estimated at $950 per clinically affected cow for a total cost of ~$737,500 for the herd during the observation period. Our results demonstrate...

#Surveillance and follow up #outcomes of #myocarditis after #mRNA #COVID19 #vaccination in #Australia

Abstract Clinical progression and medium-long term morbidity from myocarditis following mRNA COVID-19 vaccinations remains an important but undefined public health concern . We conducted prospective follow-up of individuals with either confirmed or probable myocarditis following monovalent Pfizer-BioNTech BNT162b2 or Moderna mRNA-1273 vaccination between 21 April 2021 and 5 July 2022 in Australia . Of 256 individuals who consented to follow up, mostly males following a second dose, 60% (133/221) had ongoing symptoms at 3-6 months and 35% (81/231) at 12-18 months. Self-reported ongoing exercise restrictions, medication requirements, and hospital re-presentations were associated with ongoing symptoms, as was a lower self-reported health status and quality of life. Clinical severity remained mild , with low hospitalisation rates and no deaths in the follow-up period and health-related quality of life improved over time. These findings support ongoing use of mRNA COVID-19 vaccines in at-ri...

Emergence of #Parechovirus-A5 #CNS #infections in #children from #Kansas City, #Missouri, #USA

HIGHLIGHTS •  PeV-A5 was the predominant PeV-A genotype detected from CSF/blood in 2024 at CM-KC. •  CM-KC PeV-A5 sequences resemble PeV-A5 sequences reported in Sapporo City, Japan, in 2018. •  The highest number of PeV-A5 detections within a single year in the USA. ABSTRACT Background Parechovirus-A5 (PeV-A5) blood and central nervous system (CNS) infections are rare in the United States of America (USA) and globally. We report an emergence of PeV-A5 infections among infants in Kansas City, Missouri, in 2024. Methods Cerebrospinal fluid (CSF) and blood samples from infants were tested for Parechovirus (PeV-A) in 2024 as a part of standard of care at Children's Mercy Kansas City (CM-KC). PeV-A testing included a two-step reverse transcriptase-polymerase chain reaction, and genotyping was conducted using Sanger sequencing. We analyzed the amino acid sequences and phylogeny of the 2024 PeV-A viruses and described the clinical characteristics of PeV-A infected infants. Resu...

Co-circulation of distinct high pathogenicity avian #influenza virus #subtypes in a mass #mortality event in wild #seabirds and co-location with dead #seals

Abstract H5Nx clade 2.3.4.4b high pathogenicity avian influenza viruses (HPAIV) have been detected repeatedly in Great Britain (GB) since autumn 2020, with H5N1 dominating detections but with low level detection of H5N5 during 2025. Globally, these viruses have caused mass mortalities in captive and wild avian and mammalian populations , including terrestrial and marine mammals . H5N1 has been the dominant subtype, and whilst incursions have overlapped temporally, occurrences have often been spatially distinct. Here, we report the detection of a mortality event in wild birds on the Norfolk coastline in the east of England, where H5N1 HPAIV was detected in five Great Black-backed Gulls (Larus marinus) and a Northern Fulmar (Fulmarus glacialis). Interestingly, at the same site, and as part of the same mortality event, a total of 17 Great Black-backed Gulls, one Herring Gull (Larus argentatus), one Atlantic Puffin (Fratercula arctica) and one Northern Fulmar tested positive for H5N5 HPAIV...

Extended #nirmatrelvir–ritonavir #treatment durations for immunocompromised #patients with #COVID19 (EPIC-IC): a placebo-controlled, randomised, double-blind, phase 2 trial

Summary Background Nirmatrelvir–ritonavir is approved for adults with mild-to-moderate COVID-19 who are at risk of severe disease . There are little clinical data to guide the duration of therapy in patients who are immunocompromised. We aimed to compare the approved 5-day regimen of nirmatrelvir–ritonavir with 10-day and 15-day regimens. Methods This placebo-controlled, randomised, double-blind, phase 2 trial enrolled non-hospitalised, immunocompromised individuals aged 12 years or older with symptomatic COVID-19 from 73 sites across nine countries. Participants were randomly assigned (1:1:1) to receive 300 mg nirmatrelvir and 100 mg ritonavir orally twice per day for 5, 10, or 15 days. Randomisation was stratified according to whether participants were considered immunocompromised due to use of corticosteroids or tumour necrosis factor blockers. Investigators, participants, and caregivers were masked to the assigned study group. The primary endpoint was proportion of randomly assigne...

Efficacy and safety of #obeldesivir in low-risk, non-hospitalised #patients with #COVID19 (OAKTREE): a phase 3, randomised, double-blind, placebo-controlled study

Summary Background Obeldesivir is an oral nucleoside analogue prodrug antiviral that inhibits SARS-CoV-2 replication . We aimed to assess the efficacy, safety, and tolerability of obeldesivir for the treatment of COVID-19 in non-hospitalised individuals at low risk of progression to severe disease. Methods OAKTREE was a phase 3, randomised, double-blind, placebo-controlled trial in 107 centres (including research centres, primary care centres, and hospitals) in Japan and the USA . Low-risk, non-hospitalised adults and adolescents with mild-to-moderate COVID-19 were enrolled within 3 days of symptom onset. Eligible participants were randomly assigned 1:1 using permuted block randomisation (block size of four), stratified by historical completion of a primary COVID-19 vaccination series, to receive either oral obeldesivir 350 mg or matched placebo twice daily for 5 days. The primary efficacy endpoint was time to COVID-19 symptom alleviation by day 29, which was assessed in all randomly a...

Viral #tropism is a cornerstone in the spread and #spillover of avian #influenza viruses

ABSTRACT In recent years, high pathogenicity avian influenza viruses (HPAIVs) have spread among wild, captive, and domestic birds, as well as mammals . Beyond the resulting economic and ecological losses , spillover into mammals has raised concerns about a potential pandemic . Viral tropism refers to the spectrum of host species, organs, and cells susceptible and permissive to viral infection . It is a potent driver of infection dynamics and shedding patterns, which presents important variations both between and within hosts: in poultry, HPAIV leads to systemic endothelial infection in domestic chickens , whereas neurological and selective epithelial infections are observed in domestic ducks . In mammals , infection can result in respiratory and neurological disease , but the recent outbreaks in domestic dairy cows highlighted a unique and remarkable adaptation to the mammary gland prone to viral shedding in milk. The present review explores viral tropism of HPAIV across recent spillov...

#Neurologic Manifestations Associated with #Parvovirus B19 #Epidemic, #Madrid, #Spain, 2024

Abstract A reemergence of parvovirus B19 infections in Spain in early 2024 prompted a 10-year review of the virus at a tertiary center. We identified 8 case-patients with neurologic manifestations who had parvovirus B19 in cerebrospinal fluid . Early recognition and management of parvovirus B19–associated neurologic conditions will help yield favorable outcomes. Source: US Centers for Disease Control and Prevention,  https://wwwnc.cdc.gov/eid/article/31/8/25-0278_article ____

#Influenza at the #human - #animal #interface - #Summary and #risk #assessment, from 28 May to 1 July 2025 (#WHO)

  New human cases {2}:  -- From 28 May to 1 July 2025 , based on reporting date, the detection of influenza A( H5N1 ) in nine humans , influenza A( H9N2 ) in three humans and influenza A( H10N3 ) in one human were reported officially. Additionally, one human case of infection with an influenza A(H5N1) virus was detected.  Circulation of influenza viruses with zoonotic potential in animals :  -- High pathogenicity avian influenza (HPAI) events in poultry and non-poultry continue to be reported to the World Organisation for Animal Health (WOAH).{3} The Food and Agriculture Organization of the United Nations (FAO) also provides a global update on avian influenza viruses with pandemic potential.{4}  Risk assessment {5}:  -- Sustained human to human transmission has not been reported from these events.  -- Based on information available at the time of the risk assessment, the overall public health risk from currently known influenza viruses circulating at t...

#Risk #Assessment #Report using #TIPRA - 2nd edition For Avian #influenza clade 2.3.4.4b #H5N1 #B313 viruses - Executive Summary (#WHO)

{Excerpt} 1. Background   A risk assessment exercise using the Tool for Influenza Pandemic Risk Assessment ( TIPRA ) was conducted for Clade 2.3.4.4b A(H5N1) genotype B3.13 virus in Aug – Oct 2024 .   From late 2023, unexplained illnesses were reported in dairy cattle across multiple states in the United States .  Following those events , detection of avian influenza A(H5N1) in dairy cattle from Texas was confirmed on 25 March 2024.  As of 9 December 2024 , the virus has been detected in 720 dairy cattle herds across 15 states, according to the United States Department of Agriculture (USDA), with a total of 47 human infections from poultry and dairy cattle sources, excluding 11 human cases from Washington state , that might belong to genotype D1.1, also reported.  Wild and domestic animals (e.g., cats, raccoons) near infected herds have been affected as well.  The outbreak remains uncontrolled .  Due to the unprecedented spread of the virus among ...

The Seven Deadly Sins and the Four Last Things, Hieronymus Bosch (1485)

  Public Domain. Source: WikiArt,  https://www.wikiart.org/en/hieronymus-bosch/the-seven-deadly-sins-and-the-four-last-things-1485 ____

#Thermal #tolerance and #inactivation of #Ebola virus

{Summary} HIGHLIGHTS •  The investigation demonstrated a high level of tolerance of EBOV to thermal disinfection. •  A water-bath is recommended and the tubes should be fully submerged during the process. •  The established inactivation guidelines should be followed very strictly. Dear Editor, Viruses of the genus Orthoebolavirus cause sporadic outbreaks of severe haemorrhagic fever, with case fatality rates ranging from 25% to 90% (Mahanty and Bray, 2004). Six species of the virus (Orthoebolavirus zairense, sudanense, bundibugyoense, taiense, restonense, and bombaliense) have so far been identified (Biedenkopf et al., 2023). Among these, Orthoebolavirus zairense , commonly known as Ebola virus (EBOV), stands out as the most virulent . Given its high contagiousness and lethality, EBOV must be manipulated under biosafety level 4 (BSL-4) conditions, as stipulated by the National Health Commission of the People's Republic of China's list of human pathogenic microorganisms. P...

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 challe...

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 ____

#Coronavirus Disease Research #References (by AMEDEO, July 12 '25)

  BMJ HOUSE TA Pandemic response: no one is immune to getting things wrong. BMJ. 2025;390:r1415. PubMed          BHATT N Covid-19: Indian health ministry refutes links between sudden cardiac death and vaccination. BMJ. 2025;390:r1426. PubMed          Infect Control Hosp Epidemiol NEARY M, Quan K, Tjoa T, Bittencourt CE, et al Did universal masking during the COVID-19 pandemic reduce MRSA and MSSA acquisition in the NICU? Infect Control Hosp Epidemiol. 2025 Jul 11:1-6. doi: 10.1017/ice.2025.10209. PubMed           Abstract available Int J Infect Dis BERG J, Linden K, Zaigham M, Domellof M, et al The Association between Antenatal SARS-CoV-2 Exposure and Infant Neurodevelopment at Four Months of Age: A Prospective Multicenter Cohort Survey within the COPE Study. Int J Infect Dis. 2025 Jul 3:107973. doi: 10.1016/j.ijid.2025.107973. PubMed        ...