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High pathogenicity avian influenza (HPAI) is a highly infectious and lethal disease of birds that causes systemic symptoms and has been spreading globally, including in Japan. The Okinawa rail ( Hypotaenidia okinawae ), a flightless bird endemic to Japan, is classified as an endangered species on the Red List. In 2004, the Ministry of the Environment of Japan began implementing a conservation breeding program for Okinawa rails, focusing on maintaining the species’ genetic diversity, captive breeding, and reintroduction to the wild. Given the potential for significant losses due to HPAI in Okinawa rails, the establishment of a treatment protocol as a preparedness measure is essential. The aim of this study was to determine an appropriate treatment method for HPAI in Okinawa rails using baloxavir marboxil (BXM), a drug shown to be effective in an avian laboratory model of HPAI virus infection. Single oral administration of BXM at 2.5 or 12.5 mg/kg did not produce plasma concentrations sufficient to achieve the expected therapeutic efficacy. Therefore, oral administration was deemed inadequate for generating the desired pharmacological effects. Consequently, subcutaneous administration of BXM to Okinawa rails at a dose of 2.5 or 7.5 mg/kg was explored as an alternative protocol, which resulted in higher systemic exposure compared with oral administration. Furthermore, plasma concentrations were maintained at therapeutically relevant levels up to 24 hours after subcutaneous administration at 7.5 mg/kg, with mild and reversible injection site irritation the main adverse effect. Based on these results, subcutaneous administration of BXM is proposed as a viable treatment protocol for HPAI in the conservation of endangered Okinawa rails.

High pathogenicity avian influenza virus (HPAIV) infections have been frequently reported in wild birds since 2020. Because HPAIV infection has occasionally caused outbreaks in captive rare birds, treatment using antiviral drugs has been considered from the perspective of conservation medicine. In this study, the therapeutic efficacy of baloxavir marboxil (BXM) was evaluated using a duck model to support the establishment of post-infection strategies for captive avian species. Sixteen four-week-old ducks were divided into four groups and intranasally inoculated with the HPAIV strain, A/crow/Hokkaido/0103B065/2022 (H5N1). BXM was administered orally once daily at doses of 12.5, 2.5, 0.5, or 0 mg/kg to each of the four groups from 2 to 6 days post-infection. Blood samples were collected at 2, 8, and 24 hours after the initial BXM administration to measure the plasma concentrations of its active form, baloxavir acid (BXA). All ducks were monitored until 14 days post-infection, and oral and cloacal swabs were collected for virus recovery. All eight ducks administered either 12.5 or 2.5 mg/kg of BXM survived, demonstrating a significant reduction in virus recovery compared with the 0 mg/kg group. To further characterize the relationship between BXA exposure and virus shedding, an additional experiment was conducted in which ducks received a single oral administration of BXM at doses of 7.3, 4.3, or 0.5 mg/kg at 2 days post-infection. Pharmacokinetic/pharmacodynamic analysis of BXA across all dose groups showed that reductions in virus shedding from oral swabs were positively correlated with BXA exposure, and AUC 0–24hr exhibited the strongest association. These findings demonstrate that BXM administration within 48 hours post-HPAIV infection in ducks effectively reduces mortality and virus shedding. Comparison of pharmacokinetic parameters may facilitate the estimation of optimal BXM dosing options for captive avian species.

Many high pathogenicity avian influenza (HPAI) cases in wild birds due to H5N1 HPAI virus (HPAIV) infection were reported in northern Japan in the winter of 2021–2022. To investigate the epidemiology of HPAIVs brought to Japan from surrounding areas, a genetic analysis of H5 HPAIVs isolated in northern Japan was performed, and the pathogenicity of the HPAIV in chickens was assessed by experimental infection. Based on the genetic analysis of the hemagglutinin gene, pathogenic viruses detected in northern Japan as well as one in Sakhalin, the eastern part of Russia, were classified into the same subgroup as viruses prevalent in Europe in the same season but distinct from those circulating in Asia in winter 2020–2021. High identities of all eight segment sequences of A/crow/Hokkaido/0103B065/2022 (H5N1) (Crow/Hok), the representative isolates in northern Japan in 2022, to European isolates in the same season could also certify the unlikeliness of causing gene reassortment between H5 HPAIVs and viruses locally circulating in Asia. According to intranasal challenge results in six-week-old chickens, 50% of the chicken-lethal dose of Crow/Hok was calculated as 104.5 times of the 50% egg-infectious dose. These results demonstrated that the currently prevalent H5 HPAIVs could spread widely from certain origins throughout the Eurasian continent, including Europe and the Far East, and implied a possibility that contagious viruses are gathered in lakes in the northern territory via bird migration. Active monitoring of wild birds at the global level is essential to estimate the geographical source and spread dynamics of HPAIVs.

We isolated highly pathogenic avian influenza (HPAI) H5N5 and H5N1 viruses from crows in Hokkaido, Japan, during winter 2023-24. They shared genetic similarity with HPAI H5N5 viruses from northern Europe but differed from those in Asia. Continuous monitoring and rapid information sharing between countries are needed to prevent HPAI virus transmission.

Chimeric marker vaccine candidates, vGPE−/PAPeV Erns and vGPE−/PhoPeV Erns, have been generated and their efficacy and capability to differentiate infected from vaccinated animals were confirmed in previous studies. The safety profile of the two chimeric marker vaccine candidates, particularly in the potential reversion to virulence, was evaluated. Each virus was administered to pigs with a dose equivalent to the vaccination dose, and pooled tonsil homogenates were subsequently inoculated into further pigs. Chimeric virus vGPE−/PAPeV Erns displayed the most substantial attenuation, achieving this within only two passages, whereas vGPE−/PhoPeV Erns was detectable until the third passage and disappeared entirely by the fourth passage. The vGPE− strain, assessed alongside, consistently exhibited stable virus recovery across each passage without any signs of increased virulence in pigs. In vitro assays revealed that the type I interferon-inducing capacity of vGPE−/PAPeV Erns was significantly higher than that of vGPE−/PhoPeV Erns and vGPE−. In conclusion, the safety profile of the two chimeric marker vaccine candidates was affirmed. Further research is essential to ensure the stability of their attenuation and safety in diverse pig populations.

Cattle are major reservoirs of the provisionally named influenza D virus, which is potentially involved in the bovine respiratory disease complex. Here, we conducted a serological survey for the influenza D virus in Japan, using archived bovine serum samples collected during 2010-2016 from several herds of apparently healthy cattle in various regions of the country. We found sero-positive cattle across all years and in all the prefectural regions tested, with a total positivity rate of 30.5%, although the positivity rates varied among regions (13.5-50.0%). There was no significant difference in positivity rates for Holstein and Japanese Black cattle. Positivity rates tended to increase with cattle age. The herds were clearly divided into two groups: those with a high positive rate and those with a low (or no) positive rate, indicating that horizontal transmission of the virus occurs readily within a herd. These data demonstrate that bovine influenza D viruses have been in circulation for at least 5 years countrywide, emphasizing its ubiquitous distribution in the cattle population of Japan.

Background/Objectives: Biosecurity and stamping out are key control measures against H5 high pathogenicity avian influenza (HPAI) outbreaks. Vaccination in poultry is an additional tool to reduce disease risk and facilitate timely containment. This study aimed to establish a candidate vaccine strain against H5 HPAI in Asia and validate its protective efficacy. Methods: Based on genetic and antigenic analyses, a representative HPAI virus, A/duck/Vietnam/HU16-DD3/2023 (H5N1), collected in northern Vietnam, was selected to generate a candidate vaccine strain, rgPR8/VN23HA∆KRRK-NA (rgPR8/VN23; H5N1), using reverse genetics, followed by formulation of an inactivated oil-adjuvanted vaccine. Vaccine efficacy was evaluated by measuring humoral antibody responses after intramuscular vaccination and by assessing mortality and virus recovery following intranasal challenge with a clade 2.3.4.4b virus, A/Ezo red fox/Hokkaido/1/2022 (H5N1). Results were compared with those obtained using an antigenically homologous vaccine to the challenge strain and a Japanese stockpiled vaccine. Results: All vaccinated juvenile chickens developed sufficient immunity to survive the challenge at 21 days post-vaccination. The rgPR8/VN23 (H5N1) and homologous vaccines markedly reduced virus recovery, suggesting near-sterile protection, whereas low-titer viruses were transiently detected in chickens vaccinated with the stockpiled vaccine. The rgPR8/VN23 (H5N1) vaccine conferred clinical protection in juvenile chickens as early as 8 days post-vaccination. A single dose of the rgPR8/VN23 (H5N1) vaccine provided incomplete protection in laying hens, whereas a double-volume regimen improved protective efficacy. Conclusions: The rgPR8/VN23 (H5N1) vaccine conferred strong immunity to juvenile chickens; however, a refined vaccination strategy may be required to achieve complete protection in laying hens.

In the fall of 2022, high pathogenicity avian influenza viruses (HPAIVs) were detected from raptors and geese in Japan, a month earlier than in past years, indicating a shift in detection patterns. In this study, we conducted a phylogenetic analysis on H5N1 HPAIVs detected from six wild birds during the 2022/2023 season to determine their genetic origins. Our findings revealed that these HPAIVs belong to the G2 group within clade 2.3.4.4b, with all isolates classified into three subgroups: G2b, G2d, and G2c. The genetic background of the G2b virus (a peregrine falcon-derived strain) and G2d viruses (two raptors and two geese-derived strains) were the same as those detected in Japan in the 2021/2022 season. Since no HPAI cases were reported in Japan during the summer of 2022, it is probable that migratory birds reintroduced the G2b and G2d viruses. Conversely, the G2c virus (a raptor-derived strain) was first recognized in Japan in the fall of 2022. This strain might share a common ancestor with HPAIVs from Asia and West Siberia observed in the 2021/2022 season. The early migration of waterfowl to Japan in the fall of 2022 could have facilitated the early invasion of HPAIVs.

Bovine viral diarrhea (BVD) is caused by the BVD virus (BVDV) and has been reported worldwide in cattle. To estimate BVDV circulation among cattle where few BVD cases were reported in southern Japan, 1910 serum samples collected from 35 cattle farms without a BVD outbreak were investigated to detect antibodies against BVDV-1 and BVDV-2 using an indicator virus with a cytopathogenic effect and the luciferase gene, respectively. Neutralizing antibodies against BVDV-1 and BVDV-2 were detected more frequently in 18 vaccinated farms than in 17 nonvaccinated farms. In the nonvaccinated farms, 9.6%, 1.8%, and 13.8% of the cattle were estimated to have a history of infection with BVDV-1, BVDV-2, and both, respectively. The median rate of within-herd anti-BVDV-1 seropositivity among cattle in the nonvaccinated farms was 22.0%; however, a high within-herd seropositivity (>50%) was confirmed in the two farms. The force of infection, basic reproduction number, and annual probability of BVDV-1 infection were estimated as 0.072 (95% confidence interval [CI]: 0.062–0.084), 0.36 (95% CI: 0.31–0.42), and 0.73% (95% CI: 0.61–0.87%), respectively, using the age-specific positive rate of anti-BVDV-1 antibodies. These parameters should be further applicable for developing epidemiological models which illustrate the BVDV dynamics in the field.

A previous study proved that vGPE− mainly maintains the properties of classical swine fever (CSF) virus, which is comparable to the GPE− vaccine seed and is a potentially valuable backbone for developing a CSF marker vaccine. Chimeric viruses were constructed based on an infectious cDNA clone derived from the live attenuated GPE− vaccine strain as novel CSF vaccine candidates that potentially meet the concept of differentiating infected from vaccinated animals (DIVA) by substituting the glycoprotein Erns of the GPE− vaccine strain with the corresponding region of non-CSF pestiviruses, either pronghorn antelope pestivirus (PAPeV) or Phocoena pestivirus (PhoPeV). High viral growth and genetic stability after serial passages of the chimeric viruses, namely vGPE−/PAPeV Erns and vGPE−/PhoPeV Erns, were confirmed in vitro. In vivo investigation revealed that two chimeric viruses had comparable immunogenicity and safety profiles to the vGPE− vaccine strain. Vaccination at a dose of 104.0 TCID50 with either vGPE−/PAPeV Erns or vGPE−/PhoPeV Erns conferred complete protection for pigs against the CSF virus challenge in the early stage of immunization. In conclusion, the characteristics of vGPE−/PAPeV Erns and vGPE−/PhoPeV Erns affirmed their properties, as the vGPE− vaccine strain, positioning them as ideal candidates for future development of a CSF marker vaccine.