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A cocktail #vaccine with #monkeypox virus #antigens confers protection without selecting #mutations in potential immune evasion genes in the vaccinia WR strain challenge

ABSTRACT Faced with the global monkeypox outbreak, current vaccine development predominantly focuses on the mRNA platform despite its limitations in stability and long-term efficacy. Here, we engineered a recombinant vesicular stomatitis virus (rVSV)-vectored cocktail vaccine encoding four conserved monkeypox virus (MPXV) antigens (A35R, A29L, M1R, and B6R; >94% clade homology), leveraging the thermostable properties of the VSV platform validated for 4°C storage in Ebola vaccines. In BALB/c mice , this multi-antigen vaccine elicited a rapid humoral response with specific IgG detectable by day 7, effectively neutralized the virus, and induced a robust Th1/Th2 balanced cytokine response . Immunization conferred 100% survival against lethal vaccinia virus WR strain challenge , with undetectable viral loads in the lungs and serum , and sustained efficacy against secondary infection at 60 days. Histopathology confirmed minimal lung damage in vaccinated mice . Crucially, upon the successi...

Constructing national identity in #public #health #crises: a comparative DHA study of #China and the #USA (2003–2023)

{Abstract} This study examines how China and the United States construct national identity in multilateral settings during public health crises through strategic discourse. Drawing on National Identity Theory and the Discourse Historical Approach (DHA), it analyzes speeches delivered at the United Nations General Assembly (UNGA) from 2003 to 2023, covering multiple crises including SARS, H1N1, Ebola, HIV/AIDS, and COVID-19 . Through a longitudinal and cross-crisis comparative analysis , the study reveals evolving discursive patterns that reflect shifting self–other dynamics in global health governance . China consistently constructs an identity as a cooperative, responsible major power through inclusive and multilateral language , while the United States exhibits greater variation across administrations , often framing its identity through alliance-centered and leading position . By bridging discourse-historical analysis with corpus-based methods, this research offers one of the first ...

An ultrapotent #human #antibody neutralizes all maturation states of #Zika virus

  Significance Zika virus causes microcephaly in fetuses and no vaccines or therapeutics currently exist against it . Mature and immature flavivirus particles are infectious. Here, we showed the cryoelectron microscopy (cryoEM) structures of an ultrapotent A9E human antibody , complexed with both mature (mZIKV) and immature (immZIKV) Zika virus, and the antibody neutralization mechanism . One important characteristic is that Fab A9E can distort both mZIKV and ImmZIKV particle structures. Additionally, Fab A9E or IgG A9E LALA mutant can abolish or reduce the overall infection to myeloid cells when added to other infection enhancing antibody DV62.5:immZIKV complexes. Thus, antibody A9E represents a promising potential prophylactic and therapeutic candidate , as it is effective against all maturation states of Zika virus. Abstract Zika virus (ZIKV), a flavivirus, causes a range of clinical complications including microcephaly in human fetuses . Currently, there is no treatment or vacc...

Expanding Horizons: #Host Range #Evolution and #Treatment Strategies for Highly Pathogenic Avian #Influenza #H5N1 and #H7N9

  Abstract Avian influenza viruses (AIVs), including H5N1 and H7N9, from the Orthomyxoviridae family present substantial public health concerns . The predominant circulating clade 2.3.4.4b has demonstrated enhanced capacity for mammalian adaptation , raising concerns about potential reassortment with human seasonal influenza viruses . Unlike H7N9 ’s limited host range , H5N1 infects birds, various mammals, and humans . Recent concerns include widespread H5N1 infection of U.S. dairy cattle across 18 states , affecting over 1000 herds with 71 human infections (70 H5N1 and 1 H5N5). Key observations include cow-to-cow transmission, viral presence in milk, and transmission to humans , mainly through occupational exposure . Evidence of mammal-to-mammal transmission has been documented in European and Canadian foxes and South American marine mammals . Standard pasteurization effectively inactivates the virus in milk. The continuing mammalian adaptations , particularly mutations like PB2-E...

Phylogenetic Characteristics and High Prevalence of a #Merbecovirus in #Hedgehogs from Greenspace of a Metropolis, #China

  Abstract SARS-CoV, MERS-CoV, and SARS-CoV-2 have posed tremendous threats to human health, highlighting the necessity of monitoring cross-species transmission of animal coronaviruses to humans. Hedgehogs infected with coronaviruses have been reported in several countries across Europe and Asia, raising concerns about the potential transmission of coronaviruses from hedgehogs to humans. In this study, we investigated coronavirus infections in hedgehogs inhabiting greenspaces in metropolitan Beijing and identified a Merbecovirus subgenus coronavirus with a prevalence rate of 30% (95% CI: 25–35%) among 317 hedgehogs . Phylogenetic analysis of 23 complete viral genome sequences revealed a monophyletic origin , showing close relatedness to Erinaceus hedgehog coronavirus HKU31 (Ea-HedCoV HKU31) with genome-wide nucleotide identities of 93.24–96.42%, and evidence of recombination with Tylonycteris bat coronavirus HKU4 . These findings suggest that the increase in wildlife populations as...

PA-X 122V broadly determines the #host shutoff #activity of #influenza A viruses

  ABSTRACT Multiple genes are involved in the pathogenicity of influenza A virus . Our previous study reported two naturally occurring amino acid mutations in the polymerase acidic (PA) protein as crucial determinants of the virulence of Eurasian avian-like H1N1 (EA H1N1) influenza viruses. PA-X, an accessory protein encoded by the PA gene , is thought to play a role in viral pathogenicity and regulation of host immune response , but its specific function remains unclear. In this study, we found that two genetically similar EA H1N1 influenza viruses , A/swine/Liaoning/FX38/2017 (FX38) and A/swine/Liaoning/SY72/2018 (SY72), induced significantly different suppression levels of host protein synthesis . The difference in host shutoff activity induced by PA-X protein was the key factor affecting the inhibition of host gene expression . Loss of PA-X expression significantly reduced its host shutoff activity , thereby enhancing host antiviral immune response . PA-X deficiency had no appa...

Quantifying #H5N1 #outbreak #potential and #control effectiveness in high-risk agricultural populations

  Abstract Avian influenza is a global public health threat. Since 2021, the ongoing H5N1 panzootic has brought a major shift in H5Nx epidemiology , including unprecedented spread, wide host range and lack of seasonality . Infections in marine mammals, wildlife and livestock have heightened concern for human-to-human transmission and pandemic potential . Contact tracing and self-isolation are used as public health measures in the UK to manage contacts of confirmed human cases of avian influenza. In this study, we aimed to estimate potential outbreak sizes and evaluate the effectiveness of contact tracing and self-isolation in managing community outbreaks of H5N1 following spillover from birds to people . We characterised contact patterns from an underrepresented agricultural population at high risk of avian influenza exposure through contact with birds (Avian Contact Study). Informed by these realistic social contact data, we modelled outbreak sizes using a stochastic branching pro...

Serological and viral #prevalence of #Oropouche virus (OROV): A systematic review and meta-analysis from 2000–24 including #human, #animal, and #vector #surveillance studies

  Abstract Background Oropouche virus (OROV) is an emerging arbovirus primarily transmitted by biting midges and is increasingly recognized as a public health threat in Central and South America . With over 11,000 confirmed cases reported in 2024, a ten-fold increase from the previous year, its transmission dynamics and true burden remain poorly understood due to diagnostic challenges and fragmented surveillance systems. Objective This systematic review and meta-analysis (SRMA) synthesizes OROV prevalence data in humans and summarizes the available data for vectors and animal hosts sampled between 2000 and 2024 to provide updated estimates and identify key surveillance gaps. Methods We systematically searched Web of Science, PubMed, Embase, Medline, and LILACS for OROV seroprevalence and viral prevalence studies in human, insect, and animal populations, published up to September 12, 2024. The review protocol was registered with PROSPERO (CRD42024551000). Studies were extracted in d...

#Pathobiology of Highly Pathogenic Avian #Influenza A #H5N1 Clade 2.3.4.4b Virus from #Pinnipeds on Tyuleniy Island in the Sea of #Okhotsk, #Russia

  Abstract Highly pathogenic avian influenza (HPAI) A(H5N1) clade 2.3.4.4b has recently emerged as a major threat to wildlife , agriculture, and public health due to its expanding host range and the increasing frequency of spillover into mammals . In July–August 2023, the mass death of over 3500 northern fur seals (Callorhinus ursinus) and at least one Steller sea lion (Eumetopias jubatus) was recorded on Tyuleniy Island in the Sea of Okhotsk, Russia. Two HPAI A( H5N1 ) viruses were isolated from fur seal carcasses and designated A/Northern_fur_seal/Russia_Tyuleniy/74/2023 and A/Northern_fur_seal/Russia_Tyuleniy/75/2023. Both viruses exhibited high pathogenicity in chickens (IVPI 2.7–3.0) and mice (MLD50 1.9–2.5 log10EID50/mL), with distinct differences in disease progression, histopathology, and organ tropism . Experimental infection of mice revealed that strain A/74/2023 induced more severe pulmonary and neurological lesions than A/75/2023. Whole-genome sequencing and phylogeneti...

#Coinfection of #SARS-CoV-2 and #Influenza: A Catastrophic Coexistence

  Abstract   SARS-CoV-2 is a major global public health burden associated with significant morbidity, mortality, and complications , including respiratory, cardiovascular, neurological , and digestive disorders. COVID-19 may induce venous and arterial thromboembolic complications , including deep vein thrombosis , myocardial infarction and cerebral infarction . Simultaneous myocardial and cerebral infarction, termed cardio-cerebral infarction , is exceedingly rare. There is only limited case of concurrent cardio-cerebral infarction in patients with COVID-19 . Although there is no standard treatment for the condition, antiplatelet and anticoagulation agents should be used. We emphasize the catastrophic coexistence of concurrent cardio-cerebral infarction in a patient co-infected with SARS-CoV-2 and influenza A. We described a 75-year-old woman was admitted for SARS-CoV-2 and influenza A coinfection . She received anti-viral agent treatment for the virus infection. The patient p...

A #Market-Based #Sentinel #Surveillance for an Early #Detection of Viral #Outbreaks

  Abstract Mexico has experienced recurrent viral epidemics of substantial intensity, including hyperendemic dengue, COVID-19, and recent reports of avian influenza A (H5N1) infections in birds , which pose an ongoing risk of zoonotic transmission . Mexico was also the location for the earliest detection of the pdmH1N1 virus during the 2009 influenza A pandemic. Under a One Health framework , markets represent a unique opportunity for low-cost virus monitoring at the human-animal interface . Under the hypothesis that these represent sentinel sites for an early virus detection , we implemented a pilot surveillance program at the central market of Merida city, Yucatan , Mexico, considered a regional hotspot for multiple and recent viral outbreaks . Longitudinal sampling was carried out over 11 months at 1-to-6-week intervals from April 2022 to February 2023 . We used multi-type surveillance in mosquitoes, live poultry, and wastewater . All samples were screened using RT-qPCR . Positi...

A #VSV #vector #vaccine simultaneously targeting #H5N1 HA & M2 induces robust neutralizing and ADCC #antibody responses & provides full protection vs lethal #H5N1 infection in mouse model

  Abstract Human (avian) influenza A viruses, especially highly pathogenic avian influenza (HPAI) viruses, pose a significant public health threat , and a multivalent vaccine is the primary prophylactic measure to control these viruses. To establish such a vaccine, we generated two multivalent vesicular stomatitis virus (VSV)-based vaccine candidates (V-EtM2e/H505 and V-EtM2e/H522) and characterized their ability to induce protective immune responses. Our results revealed that vaccine immunization in mice induced high humoral immune responses against both the HPAI hemagglutinin (HA) protein and the ectodomain of M2 (M2e) protein . Intriguingly, vaccine-immunized mouse sera exhibited highly efficient neutralizing activity against the corresponding H5 pseudovirus and mediated potent and broad antibody-dependent cellular cytotoxicity (ADCC) activity against M2e derived from human and avian influenza H5, H1, H3, and H7 viruses . Furthermore, both intranasal and intramuscular immunizati...

#Influenza #vaccination post - #COVID19 expands vaccine-specific effector #CD4 T-cells and Tregs under positive influence of host trained innate #immunity

  Abstract SARS-CoV-2 immunity and innate immune training may influence influenza vaccine immunogenicity . We investigated this in India . Adult volunteers with hybrid SARS-CoV-2 immunity were administered FluarixTM Tetra (GlaxoSmithKlein) 2022/2023 NH Vaccine in 2022. Significant induction of hemagglutinin inhibition-specific antibodies and polyfunctional central memory CD4+ T-cells (TCM) were observed 1-week post-vaccination with variable induction of CD8+T-cell and innate effectors. Vaccination also expanded Flu-specific regulatory T-cells (Treg), which negatively correlated with CD4 responses , highlighting vaccine immunogenicity may be subject to Treg dampening . FluarixTM did not boost SARS-CoV-2 immunity . However, SARS-CoV-2 -specific T-cell responses correlated positively with vaccine-induced T-cell responses. We evaluated trained immunity post-COVID-19 as a potential regulatory mechanism linking SARS-CoV-2 and heterologous vaccine immunogenicity . We observed, elevated fr...

Genotype A3 #influenza #H5N1 isolated from fur #seals shows high virulence in #mammals, but not #airborne transmission

  Abstract The global spread of highly pathogenic avian influenza A(H5N1) clade 2.3.4.4b viruses has recently extended to include diverse mammalian species , raising new concerns about pandemic risk . In 2023, this clade was first detected in Russian marine mammals during a mass mortality event among northern fur seals in the Far East . Genetic analyses revealed the causative viruses to belong to genotype A3 of European origin , which is known to have circulated in wild birds across the Far East since 2022. Notably, these isolates harbor the mammalian-adaptive substitutions PB2-K482R and NP-N319K—mutations previously linked to enhanced virulence in non-H5 avian influenza viruses , but whose impact on A(H5N1) clade 2.3.4.4b viruses remained to be characterized. The heightened virulence of A3 genotype viruses is confirmed by data obtained via a mouse model . However, despite these adaptive changes, ferret transmission models showed no evidence of airborne transmission of the fur seal...

#Macrolide #Resistance and P1 Cytadhesin Genotyping of #Mycoplasma pneumoniae during #Outbreak, #Canada, 2024–2025

  Abstract We investigated macrolide resistance and P1 genotypes of Mycoplasma pneumoniae during the 2024–2025 outbreak in Hamilton, Ontario, Canada . Macrolide resistance remained stable at ≈10%–20%, but significant shifts in P1 genotype distribution and resistance rates in P1 types occurred, indicating notable changes in M. pneumoniae molecular epidemiology in Ontario since 2011–2012. Source:  Link:  https://wwwnc.cdc.gov/eid/article/31/12/25-0872_article ____

#Effectiveness of the 2024–2025 #KP2 #COVID19 #vaccines in #USA during long-term follow-up

  Abstract Up-to-date estimates of COVID-19 vaccine effectiveness (VE) are needed to inform COVID-19 vaccination strategies and recommendations . This target trial emulation study aimed to estimate the long-term vaccine effectiveness (VE) of the 2024-2025 COVID-19 vaccines targeting the KP.2 Omicron variant within the Veterans Health Administration . The study population (90.9% male, mean age 70.7 years) included 538,631 pairs of vaccinated (i.e., received the KP.2 COVID-19 vaccine) and matched unvaccinated (i.e., did not receive the KP.2 COVID-19 vaccine) persons enrolled from August 2024 to January 2025. Over a mean follow-up of 172 days (range 97-232) extending to April 12, 2025, VE was low against laboratory-diagnosed SARS-CoV-2 infection ( 16.60%, 95% confidence interval [CI], 11.92-21.44), SARS-CoV-2-associated emergency department/urgent care (ED/UC) visit ( 21.05%, 95% CI, 14.22-27.21), SARS-CoV-2-associated hospitalization ( 19.53%, 95% CI 6.56-30.10) and much higher again...

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

  Abstract Since 2021, highly pathogenic avian influenza viruses (HPAIV) belonging to H5N1 clade 2.3.4.4b have caused high mortality in North American wild birds and poultry . In 2025 , a new D1.1 genotype caused two human deaths and host-switched to dairy cattle . However, the evolutionary origins and dynamics of D1.1 have not been fully characterized. Here, our phylogenetic analysis of 17,516 H5N1 genome sequences uncovers how D1.1 introduced a major shift in the antigenic diversity and ecology of the H5N1 epizootic in North America. D1.1 is the first major H5N1 genotype to (a) emerge in the Pacific flyway and spread west-to-east faster than any prior genotype; (b) antigenically shift via reassortment with the North American N1 segment, displacing the previously fixed Eurasian N1 ; and (c) transmit to a broader range of host species than any H5N1 genotype to date, introducing mammalian adaptations . Competing Interest Statement The authors have declared no competing interest. Fun...

Enhanced #genome #replication activity of pandemic #H1N1 #influenza A virus through PA #mutations

  ABSTRACT The 2009 pandemic H1N1 (pH1N1) influenza A virus (IAV) is a reassortant virus with two polymerase components, PA and PB2, originating from avian IAV . Avian IAV polymerase does not function efficiently in mammalian cells without host-adaptive mutations . The mechanism by which pH1N1 replicates in human hosts is not fully elucidated , as pH1N1 does not contain the host-adaptive PB2 E627K mutation required for species-specific interaction with ANP32 , which facilitates replicase (polymerase oligomer) formation. Our previous research revealed that mutations in PA played a key role in mammalian host adaptation of pH1N1. These mutations were found in two separate domains of PA, the C-terminal (CTD) and N-terminal domains (NTD). We reported that the NTD mutations increase the expression of NP through enhanced association of GRSF1 with the mRNA transcripts. However, the role of CTD mutations, which are located at the interface of the polymerase oligomers , has not been elucidat...

#Influenza D Virus in Black #Donkeys, Northern #China

  Abstract Influenza D virus (IDV) is prevalent in cattle in China , and a risk for spillover to other species exists. We detected IDV antibodies in 6/315 of black donkeys in northern China , suggesting cattle-to-donkey transmission and demonstrating the expanding host range of IDV and the need for reassessment of cross-species transmission risks. Source:  Link:  https://wwwnc.cdc.gov/eid/article/31/12/25-0666_article ____

Highly Pathogenic Avian #Influenza #H5N1 Clade 2.3.4.4b Virus #Infection in Poultry Farm #Workers, #Washington, #USA, 2024

  Abstract Poultry workers in Washington, USA, were infected with highly pathogenic avian influenza A(H5N1) virus and recovered. The viruses were clade 2.3.4.4b genotype D1.1, closely related to viruses causing poultry outbreaks . Continued surveillance and testing for influenza A(H5) clade 2.3.4.4b viruses remain essential for risk assessment and pandemic preparedness of zoonotic influenza viruses. Source:  Link:  https://wwwnc.cdc.gov/eid/article/31/12/25-1118_article ____