ETIDIOH - NEW

  ABSTRACT Monoclonal antibodies represent potent biological countermeasures against a wide range of human diseases ; however, their clinical application and widespread use are limited by the high cost and complexity of antibody production and manufacturing. The mRNA-lipid nanoparticle (mRNA-LNP) platform offers a versatile strategy for vaccine development and protein-replacement therapies. Since the COVID-19 pandemic, a number of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)- neutralizing antibodies have been identified, with several granted emergency use authorization for patients. Here, we report the design and generation of mRNA-LNPs encoding two SARS-CoV-2-neutralizing antibodies , 76E1 and LY1404, which, respectively, target the spike protein’s fusion peptide (FP) and receptor-binding domain (RBD). We demonstrated that a single intramuscular administration of these mRNA-LNPs in mice resulted in robust antibody production that sustained in circulation for 7–14 d...

  ABSTRACT Accurate antigenic characterization of influenza viruses is critical for vaccine strain selection but is often confounded by intrahost genetic diversity and culture-induced adaptations . We analyzed 60 A(H3N2)-positive nasopharyngeal specimens collected during the 2017–2018 influenza season to determine how virus propagation in MDCK cells affects viral genetic and antigenic properties . Deep sequencing revealed frequent genome-wide intrahost polymorphisms , including amino acid variants within major hemagglutinin (HA) antibody-binding sites . Virus propagation imposed rapid purifying selection, markedly reducing intrahost genetic diversity . Serological analyses demonstrated that these selective events altered antigenic properties, indicating that culture adaptation can alter antigenic profiles . To assess the functional impact of HA polymorphisms, we generated mixed viral populations containing defined ratios of HA-160K, HA-160T, and HA-160I variants identified in clini...

  Abstract Hemagglutinins (HA) from different influenza A virus subtypes share as little as ~40% amino acid identity , yet their protein structure and cell entry function are highly conserved . Here we examine the extent that sequence constraints on HA differ across three subtypes . To do this, we first use pseudovirus deep mutational scanning to measure how all amino-acid mutations to an H7 HA affect its cell entry function. We then compare these new measurements to previously described measurements of how all mutations to H3 and H5 HAs affect cell entry function . We find that ~50% of HA sites display substantially diverged preferences for different amino acids across the HA subtypes. The sites with the most divergent amino-acid preferences tend to be buried and have biochemically distinct wildtype amino acids in the different HA subtypes. We provide an example of how rewiring the interactions among contacting residues has dramatically shifted which amino acids are tolerated at s...

  ABSTRACT Avian influenza virus cross-species infection in humans poses a major threat to global public health . Species-specific differences between avian ANP32A and mammalian ANP32 proteins create a natural barrier against viral cross-species infection by directly impairing the functional interaction between the avian-origin viral RNA polymerase and mammalian ANP32 proteins , thereby restricting viral genome replication . The key to overcoming this barrier lies in the adaptation of viral RNA polymerase to host ANP32 family proteins . This mini-review summarizes the mechanisms and variations in influenza virus adaptation to ANP32 proteins across different species. Influenza viruses adapt to species-specific ANP32 proteins through various mutations and display distinct preferences for specific ANP32 family members within the same host. Additionally, alternative splicing variants of ANP32A within a single species further modulate viral RNA polymerase adaptability. Despite this dive...

  Abstract Introduction Prion diseases are mortal neurodegenerative disorders , which include Creutzfeldt-Jakob disease (CJD). Due to its heterogenous clinical presentation diagnosis uncertainties are common. In this paper we explore CJD diagnostic challenges focusing on differential diagnosis and diagnostic delays. Methods We report a case of a patient who was misclassified and evaluated by several medical specialties before the CJD suspicion . A systematic review of the literature of the CJD case reports focused on the timely and differential diagnosis was carried out in Medline and Embase until May 2023. Results Patient with diagnosis was made due to the form of presentation and clinical evolution , neuroimaging and the presence of protein 14-3-3 . In systematic review, fifteen articles were selected, who reported 31 cases of CJD with problems in the timely diagnosis and incorrect initial diagnosis , the main initial differential diagnoses were psychiatry exacerbation, myelopath...

  Abstract The highly pathogenic avian influenza viruses (HPAIV) of subtype H5N1 represent a major threat to animal and public health . The current panzootic with H5 clade 2.3.4.4b has caused numerous, widespread outbreaks in various domestic and wild avian species with high mortalities, massive losses and a high frequency of spillover events to unexpected novel mammalian hosts such as dairy cows . The global H5N1 situation raises serious concerns about zoonotic risks due to effective mammal-to-mammal transmission . Therefore, it is critical to increase surveillance intensity of a broadened species range, particularly at the human-animal interface . For this purpose, reliable and cost-effective serological tools that are easy to perform and suitable for high-throughput screenings are critically needed. The newly developed double antigen ELISA format employing a luminescence-based detection technology has demonstrated to comply with such prerequisites. The assay allowed the detectio...

  {Abstract} Background :  Emerging threats such as highly pathogenic influenza strains like H5N1 emphasize the need for vaccines that induce cross-reactive immunity against conserved epitopes. Existing influenza vaccines primarily elicit strain-specific responses , leaving gaps in protection against pandemic subtypes. This study aimed to evaluate T cell responses to seasonal influenza A and H5N1 and compare them to SARS-CoV-2 specific T cell responses to understand differences shaped by distinct exposure histories and vaccination strategies. Methods :  T cell responses were assessed in 41 laboratory workers who received annual seasonal influenza vaccines using ELISpot to quantify responses to peptide pools derived from influenza ( H1N1 hemagglutinin [HA], H3N2 HA, H5N1 HA, matrix protein 1 [MP1], nucleoprotein [NP]) and SARS-CoV-2 (spike [S2S], nucleocapsid [S2N]). Ten-day expansion assays were used to evaluate functional cross-reactivity between H1, H3, and H5 HA. Intra...

  Abstract Highly pathogenic avian influenza (HPAI) H5N1 clade 2.3.4.4b has expanded rapidly across the Southern Ocean since 2023 , causing extensive mortality in sub-Antarctic wildlife . Yet its penetration into Antarctica and impacts on ice-dependent species remain poorly resolved primarily due to surveillance constraints . We report the first confirmed H5N1 infection in an Antarctic ice-dependent seal (crabeater seal; Lobodon carcinophaga) and document mortality of crabeater seals across the northern Weddell Sea during November-December 2024 . Combining genomic, serological and observational data across nine species, we detected H5N1 RNA in a crabeater seal and a kelp gull (Larus dominicanus), and recovered complete HA, NA and M2 gene sequences from both. Phylogenetic analyses allowed us to identify at least two independent introductions of HPAI H5N1 clade 2.3.4.4b into the northern Antarctic Peninsula region. Serology provided strong evidence of prior exposure in scavenging bir...

Abstract Enterovirus D68 (EV-D68), a neurotropic respiratory pathogen, poses a considerable clinical threat through its link to pediatric acute flaccid myelitis (AFM) and severe respiratory illness . The possibility of recurrent epidemics , evidenced since the 2014 outbreak, remains a major concern . Genomic determinants of virulence are central to this threat. Sequence variations that affect host–receptor interactions , immune evasion, and replication efficiency serve as critical modifiers of pathogenicity. This article systematically reviews the evidence for specific genomic sites that enhance EV-D68 virulence , focusing on three critical regions: the VP1 receptor-binding site , the 2Apro/TRAF3 cleavage site, and the 3Cpro immunoregulatory region . Mutations in the VP1 receptor-binding site can alter affinity for host receptors such as sialic acid, heparan sulfate, and MFSD6 , thereby shaping viral entry and tissue tropism . Alterations in the 2Apro/TRAF3 cleavage site may impair pro...

  Antiviral Res RODRIGUEZ L, Hu Y, Li J, Han D, et al SARS-CoV-2 Resistance Analyses From the Phase 3 OAKTREE Study of Obeldesivir in Low-Risk Nonhospitalized Participants With COVID-19. Antiviral Res. 2025 Dec 29:106339. doi: 10.1016/j.antiviral.2025.106339. PubMed           Abstract available Eur J Radiol YAO J, Zhang L, Huang S, Cao S, et al Changes in the cerebral glymphatic system after rehabilitation of COVID-19 patients: A five-year follow-up study. Eur J Radiol. 2025;195:112615. PubMed           Abstract available Int J Infect Dis DAVIDO B, Mamona C, Gault E, Annane D, et al "Three of a Kind?" Unmasking the Clinical Burden of Human Metapneumovirus and Parainfluenza Virus Compared to Respiratory Syncytial Virus in Hospitalized Adults: A Pre-COVID-19 Multicenter Cohort Study. Int J Infect Dis. 2025 Dec 26:108353. doi: 10.1016/j.ijid.2025.108353. PubMed         ...

  BMC Pediatr CHEN Y, Wang Y, Tao X, Zhou M, et al Pediatric necrotizing pneumonia caused by mixed infection with influenza A virus and Panton-Valentine Leucocidin-producing Staphylococcus aureus: case report and literature review. BMC Pediatr. 2025 Dec 24. doi: 10.1186/s12887-025-06410. PubMed           Abstract available Eur J Epidemiol OSTERGREN OM, Counil E, Karimi A, Fall T, et al Who got tested and who got sick? Sociodemographic inequalities in COVID-19 testing and hospitalization among 1.48 million individuals in Sweden. Eur J Epidemiol. 2025;40:1431-1439. PubMed           Abstract available J Immunol ABE K, Holmes TH, Nguyen TT, Kim-Schulze S, et al Evaluating COVID-19 severity prediction and immune dynamics with NULISAseq: Insights from the IMPACC study. J Immunol. 2025;214:3310-3320. PubMed           Abstract available OSUAGWU AE, Payne M, Bosch J, Mbony...

Abstract Monkeypox (MPOX) is an emerging zoonotic disease caused by monkeypox virus (MPXV), an orthopoxvirus closely related to smallpox . Initially confined to endemic regions in Central and West Africa , MPOX has recently gained global significance with outbreaks reported across multiple continents . MPXV is maintained in animal reservoirs but is increasingly transmitted from person to person , facilitated by close contact, respiratory droplets , and, in some cases, sexual transmission . Clinically, MPOX presents with fever, lymphadenopathy, and a characteristic vesiculopustular rash , though atypical manifestations have been observed in recent outbreaks, complicating diagnosis. Laboratory confirmation relies on molecular testing , while differential diagnosis must consider varicella, herpes, and other vesicular illnesses. Therapeutic options remain limited ; supportive care is the cornerstone of management, but antivirals such as tecovirimat and brincidofovir, as well as smallpox va...

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...

{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 ...

  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...

  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...

  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...

  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...

  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...