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Highly pathogenic avian influenza (HPAI) H7N9 of North American wild bird lineage was detected in a commercial broiler breeder chicken flock in Mississippi . Depopulation of the affected flock is in progress. The USDA Animal and Plant Health Inspection Service (APHIS), in conjunction with State Animal Health and Wildlife Officials, are conducting a comprehensive epidemiological investigation and enhanced surveillance in response to the detection. A commercial broiler breeder premises {in Mississippi}. Clinical signs included increased mortality. Depopulation was completed 13 Mar 2025. Source: WOAH,  https://wahis.woah.org/#/in-review/6340 ____

Abstract Reports of human infections with an influenza A(H5N1) clade 2.3.4.4b virus associated with outbreaks in dairy cows in the United States underscore the need to assess the potential cross-protection conferred by existing influenza immunity . We serologically evaluated ferrets previously infected with an influenza A(H1N1)pdm09 virus for cross-reactive antibodies and then challenged 3 months later with either highly pathogenic H5N1 clade 2.3.4.4b or low pathogenicity H7N9 virus . Our results showed that prior influenza A(H1N1)pdm09 virus infection more effectively reduced the replication and transmission of the H5N1 virus than did the H7N9 virus, a finding supported by the presence of group 1 hemagglutinin stalk and N1 neuraminidase antibodies in preimmune ferrets. Our findings suggest that prior influenza A(H1N1)pdm09 virus infection may confer some level of protection against influenza A(H5N1) clade 2.3.4.4.b virus. Source: US Centers for Disease Control and Prevention,  htt...

FAO calls for increased vigilance and preparedness for avian influenza (AI) during the traditional New Year festivities that will take place across Asia on the week of 27 January 2025 . In the past year, outbreaks of AI have continued to be reported in domestic poultry, wild birds and mammals in Asia . Several AI virus subtypes including H5N1, H5N2, H5N3, H5N5, H5N6, H5N8, H7N3, H7N6, H7N8, H7N9, H10N5 , and H3N2 are currently well-established in both wild and domestic bird populations in the region. In addition, subtype H5N1 subclade 2.3.4.4b continues to circulate in both wild and domestic birds worldwide. Highly pathogenic avian influenza (HPAI) can lead to heavy losses for the poultry industry, in particular to the livelihoods of vulnerable small-scale producers . Poultry trade and related activities play a key role in AI spread and amplification in domestic bird populations, including the trade of infected live poultry and their products, handling or slaughtering infected poultry,...

Abstract H7N9 avian influenza virus (AIV) first emerged in February 2013 in China , and early isolates were all low pathogenic (LP). After circulation for a few years in live poultry markets of China , LP H7N9 AIVs evolved into a highly pathogenic (HP) form in late 2016. Deduced amino acid sequence analysis of hemagglutinin (HA) gene revealed that all HP H7N9 AIVs have obtained four-amino-acid insertion at position 339-342 (H7 numbering), making the cleavage site from a monobasic motif (LP AIVs) to a polybasic form (HP AIVs). Notably, the polybasic cleavage site motifs are diversified, of which PEVPKRKRTAR↓GLF motif is prevalent. To elucidate the reasons accounting for its dominance, recombinant H7N9 virus carrying PEVPKRKRTAR↓GLF (rJT157-2) motif was generated based on LP H7N9 virus A/chicken/Eastern China/JT157/2016 (JT157). Besides, another two viruses containing PEVPKGKRTAR↓GLF (rJT157-1) and PEIPKRKRTAR↓GLF (rJT157-3) cleavage site motifs were also constructed as comparisons. We f...

Abstract Introduction While it remains impossible to predict the timing of the next influenza pandemic , novel avian influenza A viruses continue to be considered a significant threat. Methods A Phase II study was conducted in healthy adults aged 18–64 years to assess the safety and immunogenicity of two intramuscular doses of pre-pandemic 2017 influenza A( H7N9 ) inactivated vaccine administered 21 days apart. Participants were randomized (n = 105 in each of Arms 1–3) to receive 3.75 μg, 7.5 μg or 15 μg of hemagglutinin (HA) with MF59® adjuvant, or 15 μg of HA unadjuvanted vaccine (n = 57, Arm 4). Results The three MF59 adjuvanted vaccines and the 15 μg unadjuvanted vaccine were safe and well-tolerated. Little antibody activity was detected against the A(H7N9) vaccine antigen after the first vaccination across study Arms. After second vaccination , the three adjuvanted Arms showed increases in hemagglutination inhibition (HAI), neutralizing (Neut), and neuraminidase inhibition (NAI) g...

Abstract Seasonal and pandemic influenzas are continuous threats to human health, requiring rapid development of vaccines to multiple evolving viral strains. New RNA vaccine technologies have the adaptability and manufacturability to facilitate pandemic preparedness but have limited flexibility in their route of administration, reducing the ability to establish local protective immune responses such as respiratory mucosal immunity. Here, we describe monovalent and bivalent self-amplifying RNA (saRNA) vaccines against A/Vietnam/1203/2004 H5N1 and A/Anhui/2013 H7N9. These saRNA vaccines express either H5 or H7 hemagglutinin and are formulated with a nanostructured lipid carrier (NLC) that permits both intramuscular (IM) and intranasal (IN) dosing. In mice , IM vaccination established systemic humoral and cellular responses but no detectable mucosal response , while IN administration induced robust systemic and mucosal immunity . The saRNA-NLC vaccines provided complete protection against...

Abstract Introduction Pandemic influenza vaccine development focuses on the hemagglutinin (HA) antigen for potency and immunogenicity. Antibody responses targeting the neuraminidase (NA) antigen, or the HA stalk domain have been implicated in protection against influenza. Responses to the NA and HA-stalk domain following pandemic inactivated influenza are not well characterized in humans. Material and methods In a series of clinical trials , we determine the vaccines' NA content and demonstrate that NA inhibition (NAI) antibody responses increase in a dose-dependent manner following a 2-dose priming series with AS03-adjuvanted influenza A(H7N9) inactivated vaccine (A(H7N9) IIV). NAI antibody responses also increase with interval extension of the 2-dose priming series or following a 5-year delayed boost with a heterologous adjuvanted A(H7N9) IIV. Neither concomitant seasonal influenza vaccination given simultaneously or sequentially, nor use of heterologous A(H7N9) IIVs in the 2-dos...

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 Several viruses, including influenza A virus (IAV), encode viral factors to hijack cellular RNA biogenesis processes to direct the degradation of host mRNAs, termed “host shutoff.” Host shutoff enables viruses to simultaneously reduce antiviral responses and provides preferential access for viral mRNAs to cellular translation machinery . IAV PA-X is one of these factors that selectively shuts off the global host genes. However, the specific role of PA-X host shutoff activity in viral fitness of IAV remains poorly understood. Herein, we successfully mapped PA-X 100 V as a novel site important for host shutoff of the H7N9 and H5N1 viruses . By analysing the polymorphism of this residue in various subtype viruses, we found that PA-X 100 was highly variable in H7N9 viruses. Structural analysis revealed that 100 V was generally close to the PA-X endonuclease active site , which may account for its host shutoff activity. By generating the corresponding mutant viruses derived from th...

ABSTRACT Avian influenza viruses are ubiquitous in the Anatinae subfamily of aquatic birds and occasionally spill over to poultry . Infection with low pathogenicity avian influenza viruses generally leads to subclinical or mild clinical disease. In contrast, highly pathogenic avian influenza viruses emerge from low pathogenic forms and can cause severe disease associated with extraordinarily high mortality rates. Here, we describe the natural history of avian influenza virus , with a focus on H5Nx and H7Nx subtypes , and the emergence of highly pathogenic forms; we review the biology of AIV; we examine cleavage of haemagglutinin by host cell enzymes with a particular emphasis on the biochemical properties of the proprotein convertases, and trypsin and trypsin-like proteases ; we describe mechanisms implicated in the functional evolution of the haemagglutinin cleavage site motif that leads to emergence of HPAIVs; and finally, we discuss the diversity of H5 and H7 haemagglutinin cleavage...

ABSTRACT Neutralizing antibodies (nAbs) are important for the treatment of emerging viral diseases and for effective vaccine development. In this study, we generated and evaluated three nAbs (1H9, 2D7, and C4H4) against H7N9 influenza viruses and found that they differ in their ability to inhibit viral attachment, membrane fusion, and egress . We resolved the cryo-electron microscopy (cryo-EM) structures of H7N9 hemagglutinin (HA) alone and in complex with the nAb antigen-binding fragments (Fabs) and identified the HA head-located epitope for each nAb, thereby revealing the molecular basis and key residues that determine the differences in these nAbs in neutralizing H7N9 viruses. Moreover, we found that the humanized nAb CC4H4 provided complete protection in mice against death caused by a lethal H7N9 virus infection, even when nAb was given 3 days after the mice were infected. These findings provide new insights into the neutralizing mechanism and structural basis for the rational desi...