ETIDIOH - NEW

Abstract Highly pathogenic avian influenza (HPAI) H5N1 is known for its virulence and zoonotic potential, infecting birds and mammals , thus raising public health concerns. Since 2021 its spread among birds has led to cross-species transmission causing epizootics among mammals, eventually impacting fur animal farms in Finland in 2023. To analyze the infectivity of the Finnish H5N1 isolates in human cells , representatives of diverse H5N1 isolates were selected based on the genetic differences, host animal species, and the year of occurrence. The infection kinetics of the selected H5N1 isolates from wild pheasant and fox , and fur animals blue fox and white mink were examined in human monocyte-derived dendritic cells (moDCs) with H5N1 human isolate as a control. Although the isolate from pheasant (a wild bird) showed weakly reduced replication and viral protein expression in human cells compared to mammalian isolates, no discernible differences in virus replication in moDCs was observed...

ABSTRACT The current situation with H5N1 highly pathogenic avian influenza virus (HPAI) is causing a worldwide concern due to multiple outbreaks in wild birds, poultry, and mammals. Moreover, multiple zoonotic infections in humans have been reported. Importantly, HPAI H5N1 viruses with genetic markers of adaptation to mammals have been detected. Together with HPAI H5N1, avian influenza viruses H7N9 (high and low pathogenic) stand out due to their high mortality rates in humans . This raises the question of how prepared we are serologically and whether seasonal vaccines are capable of inducing protective immunity against these influenza subtypes. An observational study was conducted in which sera from people born between years 1925–1967, 1968–1977, and 1978–1997 were collected before or after 28 days or 6 months post-vaccination with an inactivated seasonal influenza vaccine. Then, hemagglutination inhibition, viral neutralization, and immunoassays were performed to assess the basal pro...

Abstract The conserved influenza hemagglutinin stem , which is a target of cross-neutralizing antibodies , is now used in vaccine strategies focused on protecting against influenza pandemics . Antibody responses to group 1 stem have been extensively characterized, but little is known about group 2 . Here, we characterized the stem-specific repertoire of individuals vaccinated with one of three group 2 influenza subtypes ( H3, H7, or H10 ). Epitope mapping revealed two epitope supersites on the group 2 stem. Antibodies targeting the central epitope were broadly cross-reactive , whereas antibodies targeting the lower epitope had narrower breadth but higher potency against H3 subtypes . The ratio of B cells targeting each of the supersites varied with the vaccine subtype, leading to differences in the cross-reactivity of the B cell response. Our findings suggest that vaccine strategies targeting both group 2 stem epitopes would be complementary, eliciting broader and more potent protectio...

Abstract Infectious bursal disease virus (IBDV) is endemic worldwide and causes immunosuppression in chickens . We hypothesized that a previous history of IBDV in chickens would render them more susceptible to infection by influenza A viruses (IAVs) from aquatic waterfowl reservoirs . To model this, we inoculated 14 day old specific pathogen free (SPF) chickens with a low pathogenicity avian influenza (LPAI) virus strain from a mallard ( A/Mallard/Alberta/156/01 (H3N8) ) and compared replication and shedding between immunocompetent chickens and chickens that had immune dysregulation due to a prior IBDV infection with strain F52/70 (genogroup A1B1) at 2 days of age. The mallard IAV strain replicated in the upper respiratory tract of the chickens , and virus was shed from the oropharyngeal cavity , but there was no shedding from the cloaca , and no transmission to sentinel chickens . Replication of the mallard IAV in the chicken host was associated with amino acid substitutions in the po...

Highlights -- Both NA-specific antibodies and memory B cells are detected in healthy adults -- NA broad-inhibition monoclonal antibodies are derived from classical memory B cells -- Broad inhibition monoclonal antibodies target the NA conserved enzymatic epitopes -- NA broad-inhibition antibodies protect mice against H1N1 and H5N1- clade 2.3.4.4b Summary Identifying broadly reactive B precursor cells and conserved epitopes is crucial for developing a universal flu vaccine . In this study, using influenza neuraminidase (NA) mutant probes , we find that human pre-existing NA-specific memory B cells (MBCs) account for ∼0.25% of total MBCs, which are heterogeneous and dominated by class-unswitched MBCs. In addition, we identify three NA broad-inhibition monoclonal antibodies (mAbs) (BImAbs) that block the activity of NA derived from different influenza strains, including the recent cow H5N1. The cryoelectron microscopy (cryo-EM) structure shows that the BImAb targets the conserved NA enzym...

Natalia A. Ilyushina {a b}, Nicolai V. Bovin {c}, Robert G. Webster {a d}, Elena A. Govorkova  {a b} a} Department of Infectious Diseases, St. Jude Children's Research Hospital, 332 N. Lauderdale, Memphis, TN 38105-2794, USA; b} The D.I. Ivanovsky Institute of Virology, Gamaleya 16, Moscow 123098, Russia; c} Shemyakin Institute of Bioorganic Chemistry, 16/10 Miklukho-Maklaya, Moscow 117997, Russia; d} Department of Pathology, University of Tennessee, Memphis, TN 38105, USA Received 21 November 2005, Accepted 26 January 2006, Available online 21 February 2006. Abstract Rapid development of resistant influenza variants after amantadine treatment is one of the main drawbacks of M2 blockers . On the other hand, the emergence of variants with low susceptibility to the neuraminidase (NA) inhibitors is limited. In the present study we examined whether combination therapy with two classes of anti-influenza drugs can affect the emergence of resistant variants in vitro. We observed that viru...

 {Excerpt, edited} What Highly pathogenic H5N1 avian influenza A virus (HPAI H5N1) remains a low risk to the general public , and public health experts in the United States believe that available treatments and vaccines , as well as those in development, are sufficient to prevent severe disease . However, the National Institutes of Health (NIH) and its federal partners remain focused on monitoring the virus and evaluating changes , according to leading officials at the National Institute of Allergy and Infectious Diseases (NIAID), part of the NIH. In a commentary published in the New England Journal of Medicine , NIAID Director Jeanne M. Marrazzo, M.D., M.P.H., and Michael G. Ison, M.D., M.S ., chief of the Respiratory Diseases Branch in NIAID’s Division of Microbiology and Infectious Diseases, say people should find a balance between enhanced vigilance and “business as usual” with respect to HPAI H5N1 . Since 1996, HPAI H5N1 influenza viruses have circulated in at least 23 countri...

Abstract Background Highly pathogenic avian influenza A(H5N1) viruses have caused widespread infections in dairy cows and poultry in the United States , with sporadic human cases. We describe characteristics of human A(H5N1) cases identified from March through October 2024 in the United States. Methods We analyzed data from persons with laboratory-confirmed A(H5N1) virus infection using a standardized case-report form linked to laboratory results from the Centers for Disease Control and Prevention influenza A/H5 subtyping kit. Results Of 46 case patients, 20 were exposed to infected poultry , 25 were exposed to infected or presumably infected dairy cows , and 1 had no identified exposure ; that patient was hospitalized with nonrespiratory symptoms , and A( H5N1 ) virus infection was detected through routine surveillance . Among the 45 case patients with animal exposures , the median age was 34 years , and all had mild A(H5N1) illness; none were hospitalized, and none died. A total of 4...

To the Editor : Highly pathogenic avian influenza A(H5N1) viruses are circulating among wild birds and poultry in British Columbia, Canada .1 These viruses are also recognized to cause illness in humans . Here, we report a case of critical illness caused by influenza A(H5N1) virus infection in British Columbia. On November 4, 2024, a 13-year-old girl with a history of mild asthma and an elevated body-mass index (the weight in kilograms divided by the square of the height in meters) of greater than 35 presented to an emergency department in British Columbia with a 2-day history of conjunctivitis in both eyes and a 1-day history of fever . She was discharged home without treatment, but cough, vomiting, and diarrhea then developed, and she returned to the emergency department on November 7 in respiratory distress with hemodynamic instability. On November 8, she was transferred, while receiving bilevel positive airway pressure, to the pediatric intensive care unit at British Columbia Child...

Abstract Highly pathogenic avian influenza (HPAI) is a viral disease caused by some H5 and H7 subtypes of influenza virus type A in most species of birds, especially poultry. HPAI viruses are amongst the most challenging viruses that threaten both human and animal health . Consequently, various strategies such as the use of vaccines have been proposed to control the disease. After a catastrophic pandemic and the failure of conventional methods (elimination and extermination) in Iran , multiple vaccines has been used to control the disease. This study investigates the immunogenicity of two recombinant inactivated commercial vaccines of H5N1 and H5N3 subtypes in laying pullet flocks in Tehran Province, Iran . From 32 halls in 6 breeding units of laying pullets, 3200 sera and 800 tracheal and cloacal swabs were collected. After collecting the samples, Serum neutralisation (SN) and hemagglutination inhibition (HI) tests were conducted on sera to determine the serum titers of H5 specific an...

ABSTRACT   Background :  Highly pathogenic avian influenza (HPAI) (H5N1) has been endemic in Egypt for almost two decades , profoundly impacting both the poultry industry and public health. Egypt stands as a prominent epicenter for HPAI H5N1 outbreaks in Africa , marked by the highest number of positive human cases. Despite continuous governmental efforts, prior research underscored the inadequacy of strategies in controlling the virus spread.  Aim :  This study identified spatiotemporal patterns and high-risk clusters of HPAI H5N1 outbreaks at the subdistrict level.  Methods :  This study involved trial tracking of HPAI H5N1 endemicity dynamics , enabling tailored interventions at a regional level based on robust epidemiological investigations to address the persistent challenge of HPAI H5N1 in Egypt. This study illuminated spatiotemporal outbreak dynamics, with specific attention on Menofia governorate.  Results :  Despite the region’s early pou...

Abstract The GreVac system was developed as a fast and flexible plug-and-play vaccine platform based on an architecture of fully deleted (fd) helper virus-independent (hi) adenoviral (Ad) vectors . The present study established the potency of the GreVac technology. It demonstrated that the GreFluVie5 vaccine fully protected mice against lethal challenges with the A/Vietnam/1203/2004 (H5N1) pandemic avian influenza virus. The GreFluVie5 vector delivered a transgene expression cassette for the H5 hemagglutinin and N1 neuramidase influenza genes . Its fd Ad genome was carried in a capsid of the human serotype 5 (Ad5). The efficacies of three different doses and three different administration routes were compared in the mouse model. The vaccine fully protected animals against viral challenges with the wild-type A/Vietnam/1203/2004 virus, whose replication in the recipients' lungs was terminated. It induced strong immune responses. The present experiments also revealed that the intra mu...

 Two poultry farms in Normandie Region. Source: WOAH,  https://wahis.woah.org/#/in-review/6127 _____

 Backyard poultry in Tiranë Region. Source: WOAH,  https://wahis.woah.org/#/in-review/6130 _____

 A wild bird in Brandenburg Region.  Source: WOAH,  https://wahis.woah.org/#/in-review/6133 _____

Abstract Influenza, a highly contagious respiratory infectious disease caused by an influenza virus , is a threat to public health worldwide . Avian influenza viruses (AIVs) have the potential to cause the next pandemic by crossing the species barrier through mutation of viral genome. Here, we investigated the pathogenicity of AIVs obtained from South Korea and Mongolia during 2018–2019 by measuring viral titers in the lungs and extrapulmonary organs of mouse models . In addition, we assessed the pathogenicity of AIVs in ferret models . Moreover, we compared the ability of viruses to replicate in mammalian cells , as well as the receptor-binding preferences of AIV isolates. Genetic analyses were finally performed to identify the genetic relationships and amino acid substitutions between viral proteins during mammalian adaptation. Of the 24 AIV isolates tested, A/Mallard/South Korea/KNU2019-34/2019 (KNU19-34; H1N1) caused severe bodyweight loss and high mortality in mice . The virus rep...

Abstract SOBERANA-02 is a safe and effective conjugate vaccine against SARS-CoV-2 , produced using the maleimide-thiol chemistry . In this vaccine, the Cys538 in the recombinant receptor binding domain (RBD) of SARS-CoV-2 is linked, through a thiosuccinimide linker, to lysine residues of tetanus toxoid (TT) preparation . LC-MS/MS analysis revealed that TT is a complex mixture of proteins, similar to other TTs where the detoxified tetanus neurotoxin (d-TeNT) has been shown to be the most abundant protein (30-56%), regardless the quantification method used. The fifteen most abundant proteins account for approximately 78% of the total proteins. LC-MS/MS analysis of the activation process showed that 102 out of 107 lysine residues in the d-TeNT incorporated a maleimide group. In contrast, when tryptic peptides isolated by Ni2+-NTA affinity chromatography, were analyzed by LC-MS/MS, only 22 Lys residues in the d-TeNT were cross-linked to the RBD C-terminal tryptic peptide (538CVNF541-HHHHHH...

Abstract The COVID-19 pandemic has been driven by SARS-CoV-2 variants with enhanced transmission and immune escape . Apart from extensive evolution in the Spike protein , non-Spike mutations are accumulating across the entire viral genome and their functional impact is not well understood. To address the contribution of these mutations, we reconstructed genomes of recent Omicron variants with disabled Spike expression (replicons) to systematically compare their RNA replication capabilities independently from Spike. We also used a single reference replicon and complemented it with various Omicron variant Spike proteins to quantify viral entry capabilities in single-round infection assays. Viral entry and RNA replication were negatively correlated , suggesting that as variants evolve reduced entry functions under growing immune pressure on Spike, RNA replication increases as a compensatory mechanism. We identified multiple mutations across the viral genome that enhanced viral RNA replica...

As Oregon sweeps past the 1,100 cases mark, health officials remind everyone that vaccination against whooping cough is best way to prevent transmission PORTLAND, Ore.—Oregon swept past the 1,100 mark for the number of pertussis cases it’s seen during 2024 , beating its 2012 record of 910 cases in a single year—and making the need for people to stay up to date with their vaccinations all the more urgent. As of Monday, Dec. 30, Oregon Health Authority registered 1,105 cases of pertussis—also known as whooping cough —during 2024. There were 44 outbreaks , although the majority of cases were sporadic individual or household-related cases and not associated with outbreaks. The 2024 count represents the highest number of pertussis cases reported in Oregon in a single year since 1950 , when 1,420 cases were reported. Since 2003, eight Oregonians with pertussis have died . Five were younger than 4 months old, and there have been three deaths in adults – one in 2023 and two in 2024. While Oreg...

ABSTRACT The highly pathogenic avian influenza virus A(H5N1) clade 2.3.4.4b has caused a human outbreak in North America since March 2024 . Here, we conducted a serosurveillance study to determine the risk of A(H5N1) clade 2.3.4.4b (2024 cattle H5N1 ) to general population . In the initial screening of 180 serum specimens encompassing all age groups , 2.2% (4/180) had detectable neutralizing antibody (nAb) titers against 2024 cattle H5N1, with all collected from older adults aged ≥60 years old . Further screening showed that 5.0% (15/300) of adults aged ≥70 years old had detectable nAb titers against the 2024 cattle H5N1. All serum specimens with nAb titer of ≥40 had detectable HI titer, and there was a positive correlation between nAb titer and HA binding (r=0.3311, 95% confidence interval 0.2264 to 0.4283; P<0.0001). The nAb titer against seasonal H1N1 virus was 3.9-fold higher for patients with detectable H5N1 nAb than those without (geometric mean titer: 108.5 [95% CI 56.3-209.1...