ETIDIOH - NEW

ABSTRACT H1 and H3 influenza A viruses (IAVs) circulating in European pigs are markedly distinct from those circulating in other global swine populations . These viruses exhibit significant genetic diversity , further expanded by periodic interspecies transmission of IAVs from humans into pigs , followed by sustained circulation. Several zoonotic IAV infections in humans in Europe have been associated with the 1C lineage of H1 IAVs . Given the predominance of H1 detections in pigs and their zoonotic potential, we quantified antigenic evolution of H1 viruses in European pigs using ferret and pig models and assessed diversity relative to swine IAV vaccine strains. Ferret and swine antisera comparisons revealed no significant differences in antibody responses . Viruses of the 1A.3.3.2 clade exhibited reduced cross-reactivity to human seasonal vaccine strains from 2009. Viruses of the 1B.1.2.2 clade showed no cross-reactivity to the 1978 human seasonal influenza viruses nor to candidate va...

Abstract The Eurasian avian-like swine (EA) H1N1 virus has been widely prevalent in the Chinese swine population and has caused infections in human . However, knowledge regarding its pathogenic mechanisms remains limited. In this study, we analyzed the pathogenic determinants of two G4 genotype EA H1N1 viruses (A/Swine/Guangdong/SS12/2017 and A/Swine/Jiangxi/1110/2017) with differing pathogenicity by constructing a series of reassortant and mutant viruses . The HA-G219A mutation was found to be determinant of pathogenicity in mice. Subsequent analyses revealed that this mutation enhances viral replication in human cells , improves thermal stability , reduces HA activation pH, and alters receptor-binding properties . Furthermore, HA-G219A mutation may be an adaptive mutation that facilitates influenza virus adaptation to swine , with its prevalence increasing in the swine population. This mutation may support cross-species transmission of EA H1N1 swine influenza viruses or genetic excha...

Abstract Swine Influenza A Virus (IAV-S) poses a significant burden to both the pork industry and public health . Current vaccines against IAV-S are infrequently updated and induce strain-specific immunity. Computational platforms have recently emerged as a promising strategy to develop new-age vaccines. Here, we describe the Epigraph , a computationally derived and epitope optimized set of vaccine immunogens. When compared to wildtype immunogens (WT) and a commercial comparator (FluSure XP®), pigs immunized with Epigraph demonstrate significantly improved breadth and magnitude of antibody responses . Further, pigs immunized with Epigraph show more robust and a wider breadth of cross-reactive cell-mediated immune responses than pigs immunized with WT immunogens. In an experimental infection model , Epigraph immunized pigs demonstrate a significant reduction of clinical disease, lower shedding of infectious virus, reduction of lung lesions, and lower microscopic immunopathology compared...

Abstract Surveillance of influenza A viruses in pigs (SwIAV) is critical for identification of novel genetic groups that pose a risk to pig health and might have zoonotic potential . SwIAVs circulating in pigs in England between 2014 and 2021 were characterised using whole genome sequencing (WGS). Haemagglutinin (HA) and neuraminidase (NA) sequencing data from 82 of 368 influenza A positive samples (71 submissions) were determined, identifying H1N1 and H1N2 subtypes from the 1A classical swine and 1B human-seasonal lineages respectively. The 1B lineage viruses were predominant, accounting for 68.29% of sequenced viruses, with 1A lineage viruses comprising 31.71%, primarily from the 1A.3.3.2 clade (2009 H1N1 pandemic origin). This study characterised previously undefined diversity within the 1B lineage which led to the designation of new HA clades 1B.1.1.1, 1B.1.1.2 and 1B.1.1.3. Complete genome data were obtained from 64/82 viruses thereby updating the definition of genetic diversity t...

Abstract Background and Objectives :  The Netherlands faces zoonotic disease risks due to its dense human and livestock populations . The 2009 H1N1 outbreak highlighted the pandemic potential of influenza virus reassortment. Effective preparedness requires integrating behavioural and epidemiological models . Human behaviour, shaped by personal, social, and institutional factors , is critical in detecting, intervening, and treating diseases. Using the Theory of Planned Behaviour (TPB), a framework was developed integrating knowledge from the TPB to improve early detection and response, using (zoonotic) swine influenza as a case study.  Material and Methods :  Within the framework we defined the desired outcome : timely detection and notification of symptomatic (and hypothetical zoonotic) swine influenza to prevent its spread. Actions, such as symptom recognition and disease reporting, were linked to key drivers extracted from the TPB and disease transmission modelling. Exp...

Influenza at the human-animal interface Summary and risk assessment, from 21 January to 19 March 2025 {1}  New human cases {2}:  From 21 January to 19 March 2025, based on reporting date , the detection of influenza A( H5N1 ) in five humans, influenza A( H9N2 ) virus in four humans, influenza A( H1N1 ) variant ((H1N1)v) virus in one human, and influenza A( H1N2 )v virus in one human were reported officially.  • Circulation of influenza viruses with zoonotic potential in animals:  -- High pathogenicity avian influenza (HPAI) events in poultry and non-poultry continue to be reported to the World Organisation for Animal Health (WOAH).{3}  The Food and Agriculture Organization of the United Nations (FAO) also provides a global update on avian influenza viruses with pandemic potential.{4}  • Risk assessment {5}:  -- Sustained human to human transmission has not been reported from these events. Based on information available at the time of the risk assessmen...

February 2025  The development of influenza candidate vaccine viruses (CVVs),  coordinated by WHO, remains an essential component of the overall global  strategy for influenza pandemic preparedness . Selection and development of  CVVs are the first steps towards timely vaccine production and do not imply a  recommendation for initiating manufacture. National authorities may consider the  use of 1 or more of these CVVs for pilot lot vaccine production, clinical trials and  other pandemic preparedness purposes based on their assessment of public health  risk and need. Zoonotic influenza viruses continue to be identified  and evolve both antigenically and genetically, leading to the need for additional  CVVs for pandemic preparedness purposes. Changes in the antigenic and genetic  characteristics of these viruses relative to existing CVVs and their potential risks  to public health justify the need to develop new CVVs. This docume...

ABSTRACT Unexpected outbreaks caused by the H5N1 highly pathogenic avian influenza virus (HPAIV) in dairy cows in the United States (US) have raised significant veterinary and public health concerns . When and how the H5N1 HPAIV was introduced into dairy cows and the broader epidemiology of influenza A virus (IAV) infections in cattle in the US remain unclear. Herein, we performed a retrospective study to screen more than 1,700 cattle serum samples collected from different bovine breeds in the US from January 2023 to May 2024 using an enzyme-linked immunosorbent assay (ELISA) targeting the nucleoprotein (NP) to detect IAV infections, and the positive samples were further tested by hemagglutination inhibition (HI) assay . Results showed that 586 of 1,724 samples (33.99%) from 15 US states were seropositive by the NP ELISA assay , including 78 samples collected in 2024 and 508 samples collected in 2023 . Moreover, the HI assay revealed that 45 of these ELISA-positive samples were positiv...

Highlights •  Scientific question :  Cross-species transmission of influenza A viruses from swine to humans occurs occasionally because their tracheal epitheliums possess both sialic acid α-2,6-Gal and α-2,3-Gal receptors . In 2011, the first human case of swine influenza virus infection in the mainland of China was detected in Jiangsu Province . Subsequently, the Eurasian avian-like H1N1 swine influenza virus (EAH1N1 SIV) had sporadically crossed the host barrier and infected humans, raising public concern for its pandemic potential. •  Evidence before this study :  A/Jiangsu/1/2011 (H1N1v) was first discovered in 2011 and belongs to the G1 genotype. The G4 and G5 genotypes that appeared successively in 2013 are recombinant H1N1 swine influenza viruses. The EAH1N1 SIVs from 2016 to the present are dominated by the G4 genotype, with hemagglutination (HA) and neuraminidase (NA) genes derived from the EAH1N1 SIVs, non-structural protein (NS) genes derived from the trip...

Highlights •  First isolation and molecular evidence of the subtype H3N2 in swine in Colombia . •  Swine H3N2 discovered is phylogenetically divergent from other viruses. •  Colombian H3N2 was originated from an independent human-to-swine spillover. •  Sequence-based analysis reveals this is a novel antigenic variant . •  Due to antigenic variation , Colombian H3N2 possess a relevant zoonotic risk. Abstract Influenza A virus (FLUAV) affects a wide range of hosts, including humans and animals, posing a threat to public health . In swine, H3N2 subtype is associated with human-to-swine spillovers of seasonal viruses . In Latin America , the molecular and antigenic characteristics of swine FLUAV H3N2, as well as its phylogenetic origin, are poorly understood. Therefore, the objective of this study was to characterize the first swine H3N2 detected in Colombia . The origin and lineage of the virus were estimated through phylogenetic and molecular clock analyses . Anti...

Abstract In 2018, a single detection of a novel reassortant swine influenza A virus (swIAV) was made in Denmark . The hemagglutinin (HA) of the virus was from the H1N1 pandemic 2009 (H1N1pdm09) lineage and the neuraminidase (NA) from the H1N1 Eurasian avian-like swine lineage (H1N1av). By 2022, the novel reassortant virus (H1pdm09N1av) constituted 27% of swIAVs identified through the Danish passive swIAV surveillance program . Sequencing detected two H1pdm09N1av genotypes; Genotype 1 contained an entire internal gene cassette of H1N1pdm09 origin, Genotype 2 differed by carrying an NS gene segment of H1N1av origin . The internal gene cassette of Genotype 2 became increasingly dominant, not only in the H1pdm09N1av population, but also in other Danish enzootic swIAV subtypes. Phylogenetic analysis of the HA genes from H1pdm09N1av viruses revealed a monophyletic source , a higher substitution rate compared to other H1N1pdm09 viruses and genetic differences with human seasonal and other swi...

Abstract Vaccination is a common influenza A virus (IAV) control strategy for pigs. Vaccine efficacy depends on strain cross-protection and effective vaccination program implementation. We evaluated a multi-faceted IAV vaccination strategy which included (a) monthly surveillance of pigs at weaning , (b) selection of epidemiologically relevant strains from farms under surveillance, (c) updating IAV strains in custom-made vaccines, and (d) seasonal mass vaccination with custom-made vaccines given to sows in 35 farrow-to-wean farms within an integrated swine farm system. Reduction of IAV in pigs from vaccinated sows was determined by monthly monitoring of farms for 30 months by IAV rRT-PCR (PCR) testing of nasal wipes collected from litters of piglets at weaning. Hemagglutinin (HA) nucleotide and amino acid (AA) sequence homology of the circulating and vaccine strains was determined by pairwise alignment and AA comparison at antigenic sites. Of the 35 farms monitored, 28 (80%) tested posi...

{Excerpt} Novel Influenza A Virus Infections One human infection with influenza A(H1N2) variant (A(H1N2)v) virus was reported by the Iowa Department of Health and Human Services . The patient is ≥18 years of age and sought health care during the week ending January 18, 2025 (Week 3), was hospitalized , and has recovered from their illness.  An investigation by state public health officials did not identify direct or indirect swine contact by the patent.  No illness was identified among the patient's close contacts.  No human-to-human transmission has been identified associated with this case. This is the first human infection with a variant influenza virus reported during the 2024-2025 season in the United States. When an influenza virus that normally circulates in swine (but not people) is detected in a person, it is called a "variant" influenza virus.  Most human infections with variant influenza viruses occur following exposure to swine, but human-to-human transmi...

Abstract Influenza A viruses (IAV) are likely candidates for pandemics . This report summarizes the results of the Swiss national program for surveillance of influenza viruses in pigs and transmissions to humans between 2010 and 2022. Challenges and optimization options in the program are discussed. Nasal swabs or lung tissue samples from pigs with influenza-like signs (e.g. fever, cough) were screened by real-time RT-PCR for swine influenza virus (SIV) genomes, including that of the 2009 pandemic strain A(H1N1)pdm09; positive samples were subtyped for H1, N1, H3 and N2 by RT-PCR and Sanger sequencing. In parallel, humans with influenza-like symptoms and recent contact to diseased pigs were asked to self-sample themselves with a nasal swab. Human swabs were tested for IAV and positive swabs further subtyped to identify potential cross-species transmission between swine and humans. In the pigs, SIV was detected in 375 of 674 farm visits . H1N1 is the only subtype detected in Swiss pigs ...

Abstract Pigs serve as a mixing vessel for influenza viruses and can independently promote the emergence of pandemic strains in humans. During our surveillance of pig populations from 2021 to 2023 in China , 11 H1 subtype swine influenza viruses (SIVs) were isolated. All viruses were reassortants , possessing internal genes of identical origins ( PB2, PB1, PA, NP, M : pdm09/H1N1 origin, NS : North American triple reassortant origin). The H1N1 isolates were all the dominant G4 EA H1N1 viruses in China. Two H1N2 isolates carried early human pdm09/H1N1 HA genes, suggesting a possible pig-to-human transmission route. Mutations that dictate host range specificity were identified in all isolates, a phenomenon which may enhance the affinity to human receptors. These H1 subtype viruses effectively replicated both in vivo and in vitro without prior adaptation and exhibited different pathogenicity and growth characteristics. Some of the H1 viruses were even found to cause lethal infections in mi...

Abstract Influenza A virus (IAV) continuously threatens animal and public health globally , with swine serving as a crucial reservoir for viral reassortment and evolution . In Chile , H1N2 and H3N2 subtypes were introduced in the swine population before the H1N1 2009 pandemic, and the H1N1 was introduced from the H1N1pdm09 by successive reverse zoonotic events . Here, we report two novel introductions of IAV H3N2 human-origin in Chilean swine during 2023. Our study reveals a closer relationship between recent human seasonal H3N2 and novel swine strains. Interestingly, one strain maintains all the genes from the original human virus , but the other strain is already a reassortment of human H3N2 and an H1N2 previously observed on the farm. Observing global IAV sequences, a similar pattern was identified in the USA confirming the reverse zoonotic potential of current seasonal human H3N2 strains. These results highlight the importance of ongoing surveillance and reinforcing biosecurity in ...

Abstract The Eurasian avian-like (EA) H1N1 swine influenza virus (SIV) possesses the capacity to instigate the next influenza pandemic , owing to its heightened affinity for the human-type α-2,6 sialic acid (SA) receptor . Nevertheless, the molecular mechanisms underlying the switch in receptor binding preferences of EA H1N1 SIV remain elusive. In this study, we conduct a comprehensive genome-wide CRISPR/Cas9 knockout screen utilizing EA H1N1 SIV in porcine kidney cells. Knocking out the enzyme gamma glutamyl carboxylase (GGCX) reduces virus replication in vitro and in vivo by inhibiting the carboxylation modification of viral haemagglutinin (HA) and the adhesion of progeny viruses, ultimately impeding the replication of EA H1N1 SIV. Furthermore, GGCX is revealed to be the determinant of the D225E substitution of EA H1N1 SIV, and GGCX-medicated carboxylation modification of HA 225E contributes to the receptor binding adaption of EA H1N1 SIV to the α-2,6 SA receptor. Taken together, our...