History of Mass Transportation: The TN ATR 124 Diesel-Electric Multiple Unit

 

Di Moliva - Opera propria, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=154882109

Source: Wikipedia, https://it.wikipedia.org/wiki/Autotreno_TN_ATR_125

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History of Mass Transportation: The DB 111 Electric Locomotive

 

By Lars Steffens - Flickr: Baureihe 111, CC BY-SA 2.0, https://commons.wikimedia.org/w/index.php?curid=28019464

Source: Wikipedia, https://en.wikipedia.org/wiki/DB_Class_111

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#Coronavirus Disease Research #References (by AMEDEO, August 16 '25)

 

Am J Obstet Gynecol

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    Travel Med Infect Dis

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#Influenza and Other Respiratory Viruses Research #References (by AMEDEO, August 16 '25)

 

Antiviral Res

1. AL KRAD D, Stegmann KM, Dickmanns A, Kumar P, et al
   The protease inhibitor Nirmatrelvir synergizes with inhibitors of GRP78 to suppress SARS-CoV-2 replication.
   Antiviral Res. 2025 Jul 29:106247. doi: 10.1016/j.antiviral.2025.106247.
   PubMed         Abstract available
   
   
2. PATEL D, De R, Azadi N, Lee S, et al
   Discovery of broad-spectrum antivirals targeting viral proteases using in silico structural modeling and cellular analysis.
   Antiviral Res. 2025;241:106245.
   PubMed         Abstract available
   
   
3. LEBEDIN M, Petrovsky N, Tabynov K, Tabynov K, et al
   SARS-CoV-2 neutralization and protection of hamsters via nasal administration of a humanized neutralizing antibody.
   Antiviral Res. 2025;241:106235.
   PubMed         Abstract available
   
   

   
   Arch Virol

4. FERNANDEZ-ROJAS MA, Salazar AM, Ostrosky-Wegman P, Flisser A, et al
   A feedback loop between DNA damage, genomic instability, and cytoplasmic DNA sensing contributes to cytokine production in COVID-19.
   Arch Virol. 2025;170:192.
   PubMed         Abstract available
   
   

   
   Biochem Biophys Res Commun

5. ZHU H, Chen J, Dong X, Qin X, et al
   Influence of dihydrocaffeic acid and quinic acid on lung metabolism and function: Implications for dietary interventions.
   Biochem Biophys Res Commun. 2025;777:152274.
   PubMed         Abstract available
   
   
6. HODYNA D, Gryniukova A, Rogalsky S, Borysko P, et al
   Ionic liquids and lysosomotropic detergents as inhibitors of the SARS-CoV-2 main protease: QSAR modeling, synthesis and biological testing.
   Biochem Biophys Res Commun. 2025;777:152276.
   PubMed         Abstract available
   
   
7. ZHENG WH, Ni RZ, Ran XH, Mu D, et al
   Papain-like protease of SARS-CoV-2 inhibits dsRNA-induced type I interferon response partly by cleaving TBK1.
   Biochem Biophys Res Commun. 2025;777:152244.
   PubMed         Abstract available
   
   

   
   Cell

8. HUANG Y, Tan L, Liu Y, Zhao H, et al
   Response to: The mechanism for GTP-mediated RNA capping by the SARS-CoV-2 NiRAN domain remains unresolved.
   Cell. 2025;188:4462-4469.
   PubMed         Abstract available
   
   
9. SMALL GI, Darst SA, Campbell EA
   The mechanism for GTP-mediated RNA capping by the SARS-CoV-2 NiRAN domain remains unresolved.
   Cell. 2025;188:4456-4461.
   PubMed         Abstract available
   
   

   
   Epidemiol Infect

10. SMAGGE B, Labuschagne L, Pijpers J, van Roon A, et al
    Factors associated with lower COVID-19 vaccine uptake among populations with a migration background in the Netherlands.
    Epidemiol Infect. 2025;153:e87.
    PubMed         Abstract available
    
    

    
    J Infect Dis

11. ESPERSEN C, Johansen ND, Modin D, Janstrup KH, et al
    Relative effectiveness of high-dose versus standard-dose influenza vaccine against hospitalizations and mortality according to frailty score: A post-hoc analysis of the DANFLU-1 randomized trial.
    J Infect Dis. 2025 Aug 13:jiaf420. doi: 10.1093.
    PubMed         Abstract available
    
    
12. WONG JY, Cheung JK, Iuliano AD, Wu P, et al
    Influenza-associated excess mortality associated with influenza B in Hong Kong, 2014-2023.
    J Infect Dis. 2025 Aug 6:jiaf414. doi: 10.1093.
    PubMed         Abstract available
    
    

    
    J Virol

13. YAN Y, Xu J, Chen Z, Xu Y, et al
    Heat shock protein A1L restricts influenza A virus by ubiquitination of NA.
    J Virol. 2025 Aug 11:e0077125. doi: 10.1128/jvi.00771.
    PubMed         Abstract available
    
    
14. KELVIN AA, Baker PH, Ghosh S, Schultz-Cherry S, et al
    Influenza infection of the mammary gland.
    J Virol. 2025 Aug 12:e0194024. doi: 10.1128/jvi.01940.
    PubMed         Abstract available
    
    
15. DZIMIANSKI JV, Nagashima KA, Cruz JM, Sautto GA, et al
    Assessing the structural boundaries of broadly reactive antibody interactions with diverse H3 influenza hemagglutinin proteins.
    J Virol. 2025 Aug 14:e0045325. doi: 10.1128/jvi.00453.
    PubMed         Abstract available
    
    

    
    Pediatrics

16. ANTOON JW
    Influenza Antivirals: Do We Need More Evidence?
    Pediatrics. 2025 Aug 13:e2025071863. doi: 10.1542/peds.2025-071863.
    PubMed        
    
    
17. BASSETT HK, Rao S, Beck J, Brady PW, et al
    Clinician Preferences for Oseltamivir Use in Children With Influenza in the Outpatient Setting.
    Pediatrics. 2025 Aug 13:e2025071193. doi: 10.1542/peds.2025-071193.
    PubMed         Abstract available
    
    

    
    PLoS Comput Biol

18. SCIANNA M, Gallotti R, Tizzoni M, Artime O, et al
    Comparing the effectiveness of ring and block-vaccination strategies on networks.
    PLoS Comput Biol. 2025;21:e1013274.
    PubMed         Abstract available
    
    
19. TIZZANI M, Gauvin L
    Socioeconomic determinants of protective behaviors and contact patterns in the post-COVID-19 pandemic era: A cross-sectional study in Italy.
    PLoS Comput Biol. 2025;21:e1013262.
    PubMed         Abstract available
    
    

    
    PLoS One

20. NAROUEI FH, Tang Z, Wang SI, Hashmi RH, et al
    Effects of germicidal far-UVC on ozone and particulate matter in a conference room.
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21. WYPLOSZ B, Grenier B, Roche N, Roubille F, et al
    Pneumococcal vaccination at 65 years and vaccination coverage in at-risk adults: A retrospective population-based study in France.
    PLoS One. 2025;20:e0329703.
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22. SOEDER J, Preiser C, Wagner A, Neunhoffer AT, et al
    Pandemic preparedness in shaping psychosocial working conditions - insights for occupational safety and health from a longitudinal mixed-methods study during the COVID-19 pandemic at six company sites of one organization in Germany.
    PLoS One. 2025;20:e0328410.
    PubMed         Abstract available
    
    
23. BHAGAVATHI V, Ogum D, Agyabeng K, Coker-Appiah D, et al
    Unchanged but undecided: Reproductive intentions among Ghanaian women following COVID-19 lockdowns in two large metropolises in Ghana.
    PLoS One. 2025;20:e0328298.
    PubMed         Abstract available
    
    
24. TOUZET H, Privault S, Ward JK
    The role of professional socialisation in confidence in vaccines and vaccination decision-makers: Insights from a large multi-wave survey in France.
    PLoS One. 2025;20:e0328548.
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25. RASMUSSEN MGB, Just-Ostergaard E, Stidsen JV, Willaing I, et al
    What is the impact of structural changes in society on diabetes self-management and trajectories of HbA1c? A cohort study before, during and after the COVID-19 pandemic in people with diabetes treated at outpatient clinics.
    PLoS One. 2025;20:e0329394.
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26. ROY S, Biswas P, Ghosh P
    Advancing infection profiling under data uncertainty through contagion potential.
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    Proc Natl Acad Sci U S A

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    Vaccine

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    The impact of egg adaptation and immune imprinting on influenza vaccine effectiveness.
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    PubMed         Abstract available
    
    

    
    Virology

31. CHERNYSHOVA AI, Zhirnov OP
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    PubMed        
    

#USA, #Wastewater #Data for Avian #Influenza #H5 (CDC, August 15 ' 25)

 

{Summary}

Time Period: August 03, 2025 - August 09, 2025

-- H5 Detection: 2 sites (0.5%)

-- No Detection: 425 sites (99.5%)

-- No samples in last week: 33 sites

(...)

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

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A clade 2.3.4.4b #H5N1 virus #vaccine that elicits cross-protective #antibodies against conserved domains of H5 and N1 glycoproteins

Abstract

The continuous evolution and widespread dissemination of highly pathogenic avian influenza (HPAI) H5N1 viruses, particularly clade 2.3.4.4b, pose critical challenges to global pandemic preparedness. In this study, we assessed a low-dose inactivated split virus vaccine derived from clade 2.3.4.4b H5N1, formulated with an Alum/CpG adjuvant, using a preclinical mouse model. This vaccine induced potent humoral and cellular immune responses, generating high titers of cross-reactive antibodies targeting both hemagglutinin (HA) and neuraminidase (NA) glycoproteins across homologous and heterologous H5 clades. The Alum/CpG adjuvant enabled significant antigen dose-sparing while promoting a balanced Th1/Th2 immune profile. Functional analyses demonstrated strong virus neutralization, neuraminidase inhibition, and potent antibody-dependent cellular cytotoxicity activity. Additionally, the vaccine elicited robust antigen-specific CD4+ and CD8+ T cell responses and effectively controlled viral replication in the lungs, accompanied by reduced lung inflammation. Importantly, vaccinated mice were fully protected against lethal challenges with both the homologous clade 2.3.4.4b and heterologous clade 1 H5N1 viruses, despite low hemagglutination inhibition titers. Electron microscopy polyclonal epitope mapping revealed serum antibodies targeting multiple epitopes on homologous HA and NA, with some cross-reacting to conserved epitopes on heterologous proteins, underscoring broad immune recognition. Collectively, these results highlight the potential of this vaccine candidate to provide broad, multifunctional, and durable immunity against both current and emerging H5N1 threats, supporting its further development for pandemic preparedness.

Competing Interest Statement

The Icahn School of Medicine at Mount Sinai has filed patent applications regarding influenza virus vaccines on which E.P.M. and F.K. are listed as inventors. F.K. has consulted for Merck, GSK, Gritstone, Sanofi, Curevac, Seqirus and Pfizer and is currently consulting for 3rd Rock Ventures and Avimex. The laboratory of F.K. is also collaborating with Dynavax on influenza vaccine development and with VIR on influenza virus therapeutics. A.B.W. has received royalty payments for the licensure of a prefusion coronavirus spike stabilization technology for which he is a co-inventor. A.B.W. and J.H. are currently consulting for Third Rock Ventures and Merida Biosciences. The laboratory of A.B.W. received unrelated sponsored research agreements from Third Rock Ventures during the conduct of the study. The authors declare that they have no other competing interests.

Funder Information Declared

NIAID, 75N93019C00051

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.08.14.670375v1

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Detection of #antibodies specific to #H5 avian #influenza virus in a #sheep in #Norway, June 2024 ...

 

Abstract

A 2023 outbreak of highly pathogenic avian influenza in seabirds in Norway caused substantial environmental contamination of grazing areas frequented by local sheep. Eleven months later, 220 sheep were tested for antibodies to type A influenza and H5 subtype using ELISA, haemagglutination inhibition, and microneutralisation assays. One ewe (0.5%) tested positive by all methods, consistent with prior spillover infection. This underscores the importance of restricting livestock access to outbreak areas to mitigate cross-species transmission and zoonotic risk.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.08.14.670265v1

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#Italy, Integrated #Surveillance for #WNV & #Usutu Virus - Weekly Bulletin No. 5 (August 14 '25): 102 new human cases

 

{Summary}

• During current week (7-13 August '25), 102 new cases of human infection with West Nile Virus have been reported; 

• Total Number of Confirmed Cases so far this season have risen to 275 (they were 173 in the last report); 

-- among these: 

- 126 were West Nile Neuroinvasive Disease (WNND): 6 in Piedmont, 7 Lombardy, 5 Veneto, 1 FriuliVenezia Giulia, 4 Emilia-Romagna, 47 Latium, 50 Campania, 1 Basilicata, 3 Calabria, 2 Sardinia, 

- 20 asymptomatic cases among blood donors; 

- 125 West Nile Fever cases, 

- 2 asymptomatic cases and 

- 2 unspecified cases. 

• So far, 19 fatal cases were reported: 1 in Piedmont, 1 Lombardy, 8 Latium, 8 Campania, 1 Calabria. 

-- The Case-Fatality Rate of WNND cases is at 15,1% (during 2018 it was 20%, in 2024 14%). 

• No confirmed cases of Usutu Virus human infection were reported during current week. 

(...)

Source: High Institute of Health, https://www.epicentro.iss.it/westnile/bollettino/Bollettino_WND_2025_05.pdf

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Avian #Influenza #Surveillance Among Migratory #Birds, #Poultry, and #Humans Around Nansi Lake, #China, 2021–2024

Abstract

Avian influenza A viruses (AIVs) pose a significant pandemic threat due to their cross-species transmission potential. However, AIV surveillance at the critical “migratory birds–poultry-exposed population” interface remains limited. Between 2021 and 2024, we implemented a prospective One Health surveillance program around Nansi Lake, monitoring AIVs in migratory birds, poultry, and environmental samples, as well as serological investigations against representative AIVs among migratory birds or poultry-exposed subjects. AIVs were detected in 2.1% (30/1417) of migratory bird samples and 10.2% (100/978) of poultry samples. Among these, we identified ten highly pathogenic avian influenza (HPAI) H5 subtype viruses, one HPAI H7N9 virus, and five low pathogenic avian influenza (LPAI) H9N2 viruses. Phylogenetic analysis revealed evidence of frequent genomic reassortment events involving H5 subtype viruses among migratory birds, poultry, and humans. Serological investigation also suggested that both migratory birds and the poultry-exposed population had a higher risk of getting AIV infection than the general control population, especially against the H9N2 virus. Our study emphasizes the importance of strengthening continuous prospective surveillance of AIVs among migratory birds, poultry, and their exposed individuals to prevent and control potential outbreaks.

Source: Viruses, https://www.mdpi.com/1999-4915/17/8/1117

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#Polymerase #mutations underlie early #adaptation of #H5N1 #influenza virus to dairy #cattle and other #mammals.

Abstract

In early 2024, an unprecedented outbreak of H5N1 high pathogenicity avian influenza was detected in dairy cattle in the USA. As of mid-2025 the epidemic is ongoing, resulting in spillbacks into poultry, wild birds and other mammals including humans. Here, we present molecular and virological evidence that the cattle B3.13 genotype H5N1 viruses rapidly accumulated adaptations in polymerase genes that enabled better replication in bovine cells and tissues, as well as cells of other mammalian species including humans and pigs. We find evidence of several mammalian adaptations gained early in the evolution of these viruses in cattle including PB2 M631L, which is found in all cattle sequences, and PA K497R, which is found in the majority. Structurally, PB2 M631L maps to the polymerase-ANP32 interface, an essential host factor for viral genome replication. We show that this mutation adapts the polymerase to better interact with bovine ANP32 proteins, particularly ANP32A, and thereby enhances virus replication in bovine mammary systems and primary human airway cultures. Importantly, we show that ongoing evolution during 2024 and 2025 in the PB2 gene, including E627K and a convergently arising D740N substitution, further increase polymerase activity and virus replication in a range of mammalian cells. Thus, the continued circulation of H5N1 in dairy cattle not only allows virus adaption improving replicative ability in cattle but also increases the risk of zoonotic spillover.

Competing Interest Statement

The authors have declared no competing interest.

Funder Information Declared

Academy of Medical Sciences, https://ror.org/00c489v88, 1049

Royal Society, https://ror.org/03wnrjx87, 231225

Biotechnology and Biological Sciences Research Council, https://ror.org/00cwqg982, BB/Y007298/1, BB/X006123/1, BBS/E/PI/230002A, BBS/E/PI/230002B, BBS/E/PI/23NB0004, BBS/E/PI/23NB0003

Biotechnology and Biological Sciences Research Council, https://ror.org/00cwqg982, BBS/E/RL/230002C, BB/V004697/1, BB/V011286/1

Medical Research Council, MR/Y015045/1, MR/Y03368X/1, MR/X008312/1

Department for Environment Food and Rural Affairs, SE2223

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.01.06.631435v3

____

#USA, #Missouri Department of Health Confirmed a Case of Primary Amoebic #Meningoencephalitis {#PAM} (August 13 '25)

 

JEFFERSON CITY, MO – The Missouri Department of Health and Senior Services (DHSS) is announcing case of an adult Missouri resident with a laboratory-confirmed infection of Naegleria fowleri. 

Naegleria fowleri is a microscopic single-celled free-living ameba that can cause a rare deadly infection of the brain called primary amebic meningoencephalitis (PAM), also known as “brain-eating” infection. Typically, fewer than 10 people a year in the United States get PAM.

The Missouri patient is currently being treated for PAM in an intensive care unit of a hospital, and currently, no additional suspected cases of PAM are being investigated in Missouri.

The ameba is common and naturally present in warm freshwater such as lakes, rivers and ponds; however, PAM is extremely rare. Between 1962 and 2024, there were 167 reported cases of PAM in the United States.

The source of the patient’s exposure is currently being investigated by public health officials. 

While not confirmed, preliminary information implies the patient may have been water skiing at the Lake of the Ozarks days prior to becoming ill. 

Recreational water users should assume that Naegleria fowleri is present in warm freshwater across the United States; however, infection remains very rare.

Although a rare occurrence, people become infected by Naegleria fowleri when water containing the ameba enters the body through the nose from freshwater sources. 

The Naegleria fowleri ameba then travels up the nose to the brain where it damages the brain tissue. This infection cannot be spread from one person to another, and it cannot be contracted by swallowing contaminated water.

People can take actions to reduce the risk of infection by limiting the amount of water going up the nose. These actions could include:

-- Hold your nose shut, 

-- use nose clips, or 

-- keep your head above water when taking part in activities in bodies of warm freshwater, especially if you jump or dive into the water.

-- Avoid putting your head under the water in hot springs and other untreated thermal waters.

-- Avoid water-related activities in warm freshwater during periods of high-water temperature.

-- Avoid digging in, or stirring up, the sediment while taking part in water-related activities in shallow, warm freshwater areas. Naegleria fowleri amebas are more likely to live in sediment at the bottom of lakes, ponds and rivers.

-- Those who experience the following symptoms after swimming in any warm body of water should contact their health care provider immediately as the disease progresses rapidly:

- Severe headache.

- Fever.

- Nausea.

- Vomiting.

- Stiff neck.

- Seizures.

- Altered mental status.

- Hallucinations.

For more information about Naegleria fowleri, visit the CDC’s webpage. 

Source: Department of Health, https://content.govdelivery.com/accounts/MODHSS/bulletins/3edbd58

____

#COVID19-associated #neuroinflammation and #astrocyte death in the #brain linked to ORF3a-induced activation of Sur1-mediated ion channels

 

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic has disproportionately affected individuals with pre-existing medical conditions, such as neurocognitive disorders. Premorbid neurocognitive conditions compounded by COVID-19 can escalate into COVID-associated neurological complications, leading to severe illness or even death. As COVID-19 continues to persist and vaccines lose efficacy against emerging variants, individuals with neurocognitive disorders often experience prolonged symptoms that are further exacerbated by repeated breakthrough infections of highly diversified viral variants due to emergence of new viral mutations. Despite the significance of neurocognitive disorders as risk factors for COVID-19-related mortality and long COVID, the underlying causes remain largely unknown. In this study, we report a link between ORF3a expression and COVID-associated neuroinflammation and neurocytotoxicity in postmortem brain tissues from COVID-19 patients. These findings were further verified through neural cell-based in vitro and in vivo animal studies introducing ORF3a either alone or in the context of viral infection. As a membrane-associated protein, ORF3a induces upregulation of Sur1-regulated ion channels, resulting in intracellular Ca2+ influx, apoptosis, and necrosis through both NF-kB-dependent and independent proinflammatory responses in astrocytes. These findings reveal a novel clinical and mechanistic link between ORF3a and Sur1-regulated ion channels, which are highly responsive to neuroinflammatory conditions causing neurodegeneration. Additionally, we have identified a Food and Drug Administration-approved drug, glibenclamide, and a natural antiviral compound glycyrrhizin that effectively mitigates the neuropathological effects of ORF3a, underscoring the therapeutic potential and clinical significance of these findings.

Source: mBio, https://journals.asm.org/doi/full/10.1128/mbio.02012-25?af=R

____

The Differences in the Evolutionary #Dynamics of #MERS and #SARS #Coronaviruses

 

Abstract

SARS-CoV and MERS-CoV are two coronaviruses that have received significant attention due to their high pathogenicity and mortality rates in human populations. In this study, we compared their evolutionary dynamics to provide a One Health perspective on their differences in terms of the results of disease control. The phylogenetic network of SARS-CoVs showed that human isolates gathered into a “super-spreader” cluster and were distinct from civet isolates. In contrast, dromedary camel- and human-isolated MERS-CoVs were clustered together. Thus, most clades of MERS-CoV can infect humans, and MERS-CoVs seem to more easily spill over the animal-to-human interface. Additionally, the civet can be easily controlled, while the intermediate host (dromedary camels) of MERS-CoV is an important livestock species, so it is impossible to eliminate all animals. This further leads to difficulties in disease control in MERS. Although MERS-CoVs are endemic to dromedary camels in both the Middle East and Africa, human infections are mainly linked to the Middle East. The nucleotide sequences of the MERS-CoV receptor gen (dipeptidyl peptidase 4 (DPP4)) from 30 Egyptians, 36 Sudanese, and 34 Saudi Arabians showed little difference. These findings suggest that the observed disparities in MERS prevalence between populations in the Middle East and Africa may be more strongly attributed to inadequate disease surveillance and the limited camel-to-human transmission of clade C MERS-CoV in Africa, rather than variations in DPP4 gene.

Source: Viruses, https://www.mdpi.com/1999-4915/17/8/1114

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Intranasal #measles virus– and #mumps virus–based #SARS-CoV-2 #vaccine candidates prevent SARS-CoV-2 infection and #transmission

Significance

An intranasal vaccine offers many unique advantages over traditional intramuscular-delivered vaccines. Here, we developed SARS-CoV-2 Omicron XBB.1.5 spike-based monovalent and trivalent vaccines using the live attenuated measles virus (MeV) and mumps viruses (MuV) as vectors. Intranasal immunization of hamsters and mice with monovalent and trivalent vaccines induces robust and broadly neutralizing antibodies, mucosal IgA antibodies, and lung-resident memory T cells, providing complete protection of the lung and nasal turbinate against challenges with SARS-CoV-2 WA1 and Omicron subvariants XBB.1.5, EG.5, and JN.1. In addition, intranasal immunization efficiently blocks transmission of SARS-CoV-2 WA1 and Omicron XBB.1.5 among the hamsters by direct contact. Therefore, MeV- and MuV-based intranasal vaccines are highly promising next-generation COVID-19 vaccine candidates that can prevent virus infection and transmission.

Abstract

The emergence of immune-evasive SARS-CoV-2 Omicron subvariants highlights the need to develop a mucosal SARS-CoV-2 vaccine that can provide broad protection against virus infection and transmission. Here, we developed an intranasal monovalent SARS-CoV-2 vaccine expressing the six-proline-stabilized prefusion spike proteins (preS-6P) of Omicron XBB.1.5 based on the attenuated mumps virus (MuV) Jeryl Lynn (JL1) vaccine strain. We also developed an intranasal trivalent vaccine expressing the preS-6P of ancestral SARS-CoV-2 WA1 and two Omicron subvariants, BA.1 and XBB.1.5, using the attenuated measles virus (MeV) and MuV-JL1 and JL2 vaccine strains, respectively. Intranasal immunization of hamsters with the monovalent rMuV-JL1-XBB.1.5 or the trivalent vaccine induced high levels of neutralizing antibodies (NAbs) that efficiently neutralized Omicron subvariants XBB.1.5, EG.5, and JN.1, providing complete protection against these Omicron subvariants. Similar levels of Omicron XBB.1.5 NAbs were detected in monovalent rMuV-JL1-XBB.1.5 and trivalent vaccine groups even when hamsters had been preimmunized with the rMuV-JL2-WA1 vaccine, suggesting that both intranasal vaccines are effective in the presence of immune imprinting induced by the spike of SARS-CoV-2 WA1. Intranasal, but not subcutaneous, immunization generated high levels of S-specific mucosal IgA antibodies as well as lung-resident memory T cells in IFNAR1−/− mice. Finally, intranasal immunization with the trivalent vaccine efficiently blocked transmission of SARS-CoV-2 WA1 and Omicron XBB.1.5 among hamsters in a direct contact transmission setting. In summary, we have developed intranasal MeV and MuV-based trivalent vaccines that induce broad NAbs, robust mucosal immunity, and strong protection against both virus challenge and virus transmission.

Source: Proceedings of the National Academy of Sciences of the United States of America, https://www.pnas.org/doi/abs/10.1073/pnas.2506821122?af=R

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#Pigeons exhibit low susceptibility and poor #transmission capacity for #H5N1 clade 2.3.4.4b high pathogenicity avian #influenza virus

 

Abstract

The ongoing panzootic of H5N1 high pathogenicity avian influenza virus (HPAIV) has caused the deaths of over half a billion wild birds and poultry, and has led to spillover events in both wild and domestic mammals, alongside sporadic human infections. A key driver of this panzootic is the apparent high viral fitness across diverse avian species, which facilitates an increased interface between wild and domestic species. Columbiformes (pigeons and doves) are commonly found on poultry premises, yet little is known about their potential role in contemporary HPAIV disease ecology. Here we investigated the epidemiological role of pigeons (Columba livia) by determining their susceptibility using decreasing doses of clade 2.3.4.4b H5N1 HPAIV (genotype AB). We investigated infection outcomes and transmission potential between pigeons and to chickens. Following direct inoculation, pigeons did not develop clinical signs, and only those inoculated with the highest dose shed viral RNA or seroconverted to H5N1-AB, revealing a MID50 of 105 EID50. Even in the high-dose group, only low-level shedding and environmental contamination was observed, and low-level viral RNA were present in the tissues of directly inoculated pigeons, with no distinct pathological lesions. Pigeons did not transmit the virus to pigeons or chickens placed in direct contact. We observed distinct differences in sialic acid receptor distribution in the pigeon respiratory tract compared to chickens and ducks. Together, these findings suggest that pigeons have low susceptibility to clade 2.3.4.4b H5N1 HPAIV and are unlikely to contribute significantly to virus maintenance, transmission to poultry, or zoonotic infection.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.05.02.651910v2

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Tracking HPAIV #H5 through a geographic #survey of #Antarctic #seabird populations

Abstract

An extensive survey for the detection of Highly Pathogenic Avian Influenza virus (HPAIV) H5 in seabird species is reported here. It was conducted between December 2023 and January 2024, in thirteen breeding sites spanning from the northeastern sector of the Antarctic Peninsula to the Ross Sea, including the coasts of the Bellingshausen Sea and the Amundsen Sea. Nine individuals from Pygoscelis adeliae and Leucocarbo bransfieldensis tested positive for RT-PCR amplification of a H5 segment of HPAIV in two different locations on the Antarctic Peninsula. This study suggests the possibility of the first cases of HPAIV H5 in the Antarctic continent, potentially adding two new species to the list of infected species. It also highlights the southernmost suspected cases identified to date of surveillance, and notably, no cases were detected between the Antarctic Peninsula and the Ross Sea.

Source: Scientific Reports, https://www.nature.com/articles/s41598-025-14651-3

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The (#digestive) path less traveled: #influenza A virus and the #gastrointestinal tract

 

ABSTRACT

Influenza A virus (IAV) infection of the respiratory tract can cause both respiratory and non-respiratory symptoms. Gastrointestinal (GI) symptoms such as diarrhea, vomiting, and abdominal pain can occur in persons with seasonal influenza A or novel IAV infections, but the extent to which IAVs can infect and replicate in GI tissues is understudied. The ongoing outbreak of A(H5N1) IAV in US dairy cattle associated with sporadic human infections has highlighted the potential public health threat posed by the introduction of infectious virus into materials that may be consumed by humans, such as milk. Here, we review epidemiologic reports documenting the frequency of GI complications in humans infected with seasonal and novel IAVs and present laboratory studies supporting the capacity of IAV to replicate in mammalian GI tissues, with an emphasis on A(H5N1) viruses. Studies assessing the ability of IAV to cause mammalian infection following consumption of virus-containing material are also presented. Collectively, these studies suggest that gastric exposure represents a potential non-respiratory route for A(H5N1) IAVs in mammals that can lead to infection and support that IAV may be detected in mammalian intestinal tissues following multiple exposure routes.

Source: mBio, https://journals.asm.org/doi/full/10.1128/mbio.01017-25?af=R

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#Influenza #infection of the mammary #gland

 

ABSTRACT

The mammary gland is an essential organ for milk production, providing essential immune and nutritional support to offspring and supplying dairy products for human consumption. In both humans and animals, the lactating mammary gland is susceptible to bacterial and viral infections, which can lead to mastitis and, in some cases, vertical transmission to offspring, with potential adverse effects on infant health. However, until recently, the role of respiratory viruses in mammary gland infection has been relatively understudied, particularly their ability to infect mammary epithelial cells and transmit through lactation. The recent emergence of highly pathogenic avian influenza H5N1 clade 2.3.4.4b in dairy cattle has demonstrated the virus’s capacity to replicate in the mammary gland, cause mastitis, and produce high viral loads in milk. This raises significant concerns about the potential for zoonotic transmission to humans and other animals in contact with infected dairy cows and unpasteurized milk. In this mini-review, we highlight key studies that demonstrate the replication of influenza and other viruses in the mammary gland, summarize recent findings from experimental and natural H5N1 clade 2.3.4.4b infections in dairy cows and small animal models, and discuss the broader One Health implications of the current H5N1 outbreak. We emphasize the urgent need for an interdisciplinary collaboration across sectors to mitigate the risks posed by influenza viruses with pandemic potential.

Source: Journal of Virology, https://journals.asm.org/doi/full/10.1128/jvi.01940-24?af=R

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Estimated #transmission #dynamics of #SARS-CoV-2 #variants from #wastewater are unbiased and robust to differential shedding

 

Abstract

The COVID-19 pandemic has accelerated the development and adoption of wastewater-based epidemiology. Wastewater samples can provide genomic information for detecting and assessing the spread of SARS-CoV-2 variants in communities and for estimating important epidemiological parameters such as the selection advantage of a viral variant. However, despite demonstrated successes, epidemiological data derived from wastewater suffers from potential biases. Of particular concern are shedding profiles, which can affect the relationship between true viral incidence and viral loads in wastewater. Changes in shedding between variants may decouple the established relationship between wastewater loads and clinical test data. Using mathematical modeling, simulations, and Swiss surveillance data, we demonstrate that estimates of the selection advantage of a variant are not biased by shedding profiles. We show that they are robust to differences in shedding between variants under a wide range of assumptions, and identify specific conditions under which this robustness may break down. Additionally, we demonstrate that differences in shedding only briefly affect estimates of the effective reproduction number. Thus, estimates of selective advantage and reproduction numbers derived from wastewater maintain their advantages over traditional clinical data, even when there are differences in shedding among variants.

Source: Nature Communications, https://www.nature.com/articles/s41467-025-62790-y

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#Mpox: disease #manifestations and therapeutic #development

 

ABSTRACT

Mpox, caused by monkeypox virus (MPXV) infection, has emerged as a significant global health threat. The World Health Organization (WHO) has twice declared a Public Health Emergency of International Concern for mpox: first for the 2022–2023 global outbreak and subsequently for concurrent outbreaks in Africa. Beyond MPXV, other members of the Orthopoxvirus genus also pose growing risks of zoonotic spillover, with the potential to jump from animal reservoirs to humans. Clinically, mpox is distinguished from other Orthopoxvirus infections by its propensity to cause severe systemic manifestations alongside localized skin lesions, disproportionately affecting vulnerable groups such as children, pregnant women, and immunocompromised individuals. Although vaccines are available, effective therapeutics are equally essential in combating the mpox crisis. Current antiviral agents, including tecovirimat and brincidofovir, have demonstrated uncertain or disappointing efficacy in preclinical and clinical studies, underscoring the urgent need for further therapeutic development. This review provides a concise synthesis of recent advances in understanding mpox epidemiology and clinical features and offers an in-depth discussion of the current status and future directions in therapeutic development. We highlight the importance of innovative experimental models that can authentically replicate mpox disease manifestations and serve as robust platforms for therapeutic testing. Advancing these research efforts is critical for responding to the ongoing mpox emergency and for sustaining preparedness against future poxvirus epidemics.

Source: Journal of Virology, https://journals.asm.org/doi/full/10.1128/jvi.00152-25?af=R

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Quantifying viral #pandemic #potential from experimental #transmission studies

 

Abstract

In an effort to avert future pandemics, surveillance studies aimed at identifying zoonotic viruses at high risk of spilling over into humans act to monitor the "viral chatter" at the animal-human interface. These studies are hampered, however, by the diversity of zoonotic viruses and the limited tools available to assess pandemic risk. Methods currently in use include the characterization of candidate viruses using in vitro laboratory assays and experimental transmission studies in animal models. However, transmission experiments yield relatively low-resolution outputs that are not immediately translatable to projections of viral dynamics at the level of a host population. To address this gap, we present an analytical framework to extend the use of measurements from experimental transmission studies to generate more quantitative risk assessments. Specifically, we use within-host viral titer data from index and contact animals to estimate parameters relevant to transmission, including an estimate of transmissibility. We then extended this model to estimate epidemiological parameters, such as the basic reproductive number and generation interval. To illustrate these approaches, we present them in the context of two influenza A virus (IAV) ferret transmission experiments: one using influenza A/California/07/2009 (Cal/2009) and one using influenza A/Hong Kong/1/1968 (Hong Kong/1968). Despite estimating broadly similar transmissibilities for Cal/2009 and Hong Kong/1968, we conclude that Cal/2009 has a higher pandemic potential. This difference in pandemic potential seems to be primarily driven by its more robust within-host replication. Our results critically depend on several assumptions, namely that the within-host viral dynamics in humans and those in the model animal used (here, ferrets) share quantitative similarities and that viral transmissibility between model animals reflects viral transmissibility between humans. The methods we present to assess relative pandemic risk across viral isolates can be used to improve quantitative risk assessment of other emerging viruses of pandemic concern.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.03.24.645081v2

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#UK - High pathogenicity avian #influenza #H5N1 viruses (#poultry) (Inf. with) - Immediate notification

 

{By gary noon - Flickr, CC BY-SA 2.0, https://commons.wikimedia.org/w/index.php?curid=4077294}

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{England, Devon} Premises with 5200 pheasants. Increased mortality, reduced water consumption and other clinical signs were reported. Samples were taken and were tested positive for HPAI H5N1.

Source: WOAH, https://wahis.woah.org/#/in-review/6716

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Decoding non-human #mammalian adaptive #signatures of 2.3.4.4b #H5N1 to assess its #human adaptive potential

ABSTRACT

The 2.3.4.4b clade highly pathogenic avian influenza H5N1 infected diverse non-human mammalian species, gained mammal-to-mammal transmission potential, and caused sporadic human infections. However, whether non-human mammals enable the human adaptation of 2.3.4.4b H5N1 to establish human infections is unclear. Gain-of-function research restrictions may hinder the assessment of 2.3.4.4b H5N1 human adaptations. Here, we tracked the evolution of 2.3.4.4b H5N1 that infected non-human mammals and evaluated their ability to gain human adaptations. The non-human mammal 2.3.4.4b H5N1 partly acquired classical human-adapting mutations, which are identical to the residues of H1N1pdm09 and seasonal human H3N2 viruses, while showing a few species-specific adaptations that might be potential barriers for successful human infections. The polymerase complex proteins, PA and PB2, acquired human adaptations in non-human mammals, with fox-infected viruses showing more positive selection in the polymerase complex. The human-adapting Q591K/R substitution in PB2 appeared only in the 2.3.4.4b clade but not in previously circulating H5N1 strains. Despite minimal changes in hemagglutinin (HA), A160T and T199I mutations near the receptor binding site of HA in dairy cattle viruses indicate the rapid HA glycan surface evolution affecting virus entry and immune evasion. The unbiased quantitative assessment of virus adaptations indicated that 2.3.4.4b H5N1 circulating in bears, cattle, dolphins, and foxes might show better human adaptive potential. Thus, 2.3.4.4b H5N1 appears to be acquiring human adaptations due to natural selection pressure in non-human mammals. Overall, our study delineates human adaptation and infection risk of specific non-human mammalian circulating 2.3.4.4b H5N1 strains.

IMPORTANCE

The 2.3.4.4b clade H5N1 virus emerged as a panzootic strain, leading to the unprecedented deaths of domestic and wild birds and diverse non-human mammalian species. Intriguingly, the 2.3.4.4b H5N1 transmitted to diverse mammalian species and gained mammal-to-mammal transmission, suggesting its pandemic potential. The H5N1 outbreaks in dairy cattle and sea lions are devastating, and they contributed to sporadic human infections. This indicates the ability of non-human mammal hosts, like dairy cattle, as potential sources for human transmission. However, the signatures of non-human mammal adaptations of 2.3.4.4b H5N1 and how these adaptations drive the human adaptive potential of 2.3.4.4b H5N1 are unclear. In this study, we show the specific molecular patterns of H5N1 proteins that determine species-specific adaptations in non-human mammals. We identified that 2.3.4.4b H5N1 circulating in non-human mammals is rapidly evolving with critical adaptations in PA, PB2, and HA and gaining human adaptive potential in specific non-human mammalian species.

Source: Microbiology Spectrum, https://journals.asm.org/doi/10.1128/spectrum.00948-25

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#COVID19 #pandemic resulted in more metastatic #breast #cancer cases at #diagnosis

Abstract

The study aimed to assess the impact of the COVID-19 pandemic on breast cancer diagnosis, tumor characteristics, and staging in an Eastern-European country. This retrospective study included 11,635 breast cancer patients and clients presenting between March 2019 and March 2022. Patients were categorized into pre-pandemic, pandemic, and post-pandemic groups. Data included age, sex, pathology, tumor characteristics (histologic type, grade, ER/PR/HER2 status), and TNM staging. Statistical analysis compared these parameters across the three-time intervals. During the pandemic, breast cancer diagnosis decreased significantly compared to the pre-pandemic period (9.1% vs. 13.17%, p < 0.001) but increased post-pandemic (11%, p = 0.013). Invasive ductal carcinoma of non-special type (IDC-NST) was predominant in all three-time periods. Aggressive tumors (Nottingham grade 3, ER negative) increased during the pandemic and post-pandemic times. Molecular subtypes showed variations across time intervals, with triple-negative tumors rising significantly. Larger tumors, increased lymph node involvement (9–19%), and distant metastasis characterized the pandemic and post-pandemic periods. Compared to pre-pandemic patients, post-pandemic ones were 7 times more likely to be metastatic at diagnosis (p < 0.05). The COVID-19 pandemic led to a significant decrease in breast cancer diagnosis, particularly during the pandemic period. Tumors appeared more aggressive, with higher lymph node and distant metastatic involvement. The long-term prognosis and healthcare cost implications remain uncertain. These findings emphasize the need for adapted cancer screening programs and healthcare system readiness during pandemics. COVID-19 pandemic has resulted in a lower detection rate among patients diagnosed with breast cancer and increased TNM stage.

Source: Scientific Reports, https://www.nature.com/articles/s41598-025-14582-z

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The Abbey in the Oakwood, Caspar David Friedrich (1809 - 1810)

 

Public Domain.

Source: WikiArt, https://www.wikiart.org/en/caspar-david-friedrich/the-abbey-in-the-oakwood

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History of Mass Transportation: The DB VT 11.5 Autotrain

 

By Benedikt Dohmen (User:Benedictus), Archiv-Nr. 92/39 - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=496875

Source: Wikipedia, https://en.wikipedia.org/wiki/DB_Class_VT_11.5

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Companion #animals and #H5N1 highly pathogenic avian #influenza: cause for #concern?

Abstract

The first known human infection with a highly pathogenic H5N1 influenza A virus appeared in China in 1997. Between 2003 and 2017, the WHO documented an additional 862 human cases, mainly from southeast Asia and Egypt, with a mean annual case fatality rate of 56%. By 2006, the susceptibility of cats to severe respiratory and neurologic disease became apparent. Scientists raised concerns regarding the potential for domestic cats to transmit novel pathogenic strains to humans. But after 2006, reports of new H5N1 infections in companion animals dwindled, and human cases fell after 2016. In 2021, H5N1 clade 2.3.4.4b viruses suddenly appeared in Europe and spread rapidly to the Americas, wreaking havoc on wildlife and crippling the poultry and dairy industries. Between 2022 and 2025, dozens of domestic cats died, most often following raw food consumption. Unease regarding the transmission potential of pets resurfaced. Although most human infections in the Americas were mild and associated with poultry or dairy contact, the recent detection of genotype D1.1 in association with severe illness or death is cause for concern. Genotype D1.1 has now also been detected in dairy cattle and domestic cats. Reports of H5N1 clade 2.3.2.1a viruses in India suggest a new potential threat. Successful control of H5N1 infections is strongly dependent on a One Health approach. Small animal veterinarians play a key role in this approach through recognition of cases and education of pet owners, thus preserving the human-animal bond.

Source: Journal of American Veterinary Medicine Association, https://avmajournals.avma.org/view/journals/javma/aop/javma.25.06.0388/javma.25.06.0388.xml?tab_body=abstract

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