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Japan: Updated HPAI H5 Risk Assessment & Pre-pandemic Vaccine Selection
#18,421
In May of last year we looked at plan by Japan's MOH To Stockpile 10 Million Doses of H5N1 Vaccine, enough to vaccinate about about 8% of their population. The MOH outlined their rationale for this in the following (translated) statement:
HPAIV (H5N1) has not acquired the ability to efficiently transmit from person to person, and is unlikely to lead to a pandemic in humans at this time. Since many cases of infection with HPAIV (H5N1) have been reported, the chances of human exposure to HPAIV (H5N1) are increasing, and there is a high possibility that sporadic cases of human infection will continue to be reported.
Since then, the number of sporadic human infections have increased markedly, as have reports of HPAI H5 infection in a growing array of mammalian species (see USDA H5N1 in Mammalian Wildlife).
A number of other countries, including the UK, Canada, the United States and the EU have also announced plans to stockpile limited quantities of HPAI H5 vaccine. Since these vaccines have a limited shelf life, and these viruses continue to evolve, it is impractical to stockpile large quantities.
But having some quantity of pre-existing vaccine on hand could allow certain high risk individuals (like farmers or HCWs) to be partially protected while an updated vaccine is being developed.
Today Japan's Ministry of Health, Labour & Welfare released an extensive set of documents (all in Japanese) on findings by their Health Sciences Committee's 23rd Subcommittee on New Influenza Measures. First the links, then some (translated) excerpts.
The risk assessment & response document (below) runs 29 pages, and covers a lot of territory. I've posted excerpts from the summary from the National Institute of Infectious Diseases below (note: machine translations are sometimes syntax-challenged).
The document on Future types of pre-pandemic vaccines to be stockpiled (draft) focuses on a local strain from an infected fox with viral meningoencephalitis and demonstrating virus growth in the upper airway, collected on Hokkaido in 2022.
Worth noting, the CDC remarked last December that the HA of the virus that produced a fatal case in Louisianawas similar to this Japan isolate.
Overall, the hemagglutinin (HA) sequences from the two clinical specimens were closely related to HA sequences detected in other D1.1 genotype viruses, including viruses sequenced from samples collected in November and December 2024 in wild birds and poultry in Louisiana. The HA genes of these viruses also were closely related to the A/Ezo red fox/Hokkaido/1/2022 candidate vaccine virus (CVV) with 2 or 3 amino acid changes detected.
Once again due to its length, I've only produced some excerpts from this CVV report.
The vaccine candidate strains indicated by WHO among the Clade 2.3.4.4b epidemic worldwide are H5N8 A/Astrakhan/3212/2020 (IDCDC-RG71A), H5N6 A/Fujian-Sanyuan/21099/2017 (CNICFJ21099), H5N1 A/chicken/Ghana/AVL-763_21VIR7050-39/2021, A/American w i g e o n / S o u t h C a r o l i n a / 2 2 - 0 0 0 3 4 5 - 0 0 1 / 2 0 2 1 ( I D C D C - RC78 ), A / E z o r e d fox/Hokkaido/1/2022 (NIID-002), A/Jiangsu/NJ210/2023 (CNIC-JSNJ210).
Although the risk of seeing an H5N1 pandemic is considered low today, that assessment could easily change, and the risk is considered great enough that governments are spending hundreds of millions of dollars to prepare.
As Maggie Fox explained last fall in SCI AM - A Bird Flu Vaccine Might Come Too Late to Save Us from H5N1, our options during the opening months of any pandemic will be limited. Novel vaccine production could easily take months, and we've seen failures to meet goals or deadlines in the past (see Manufacturing Pandemic Flu Vaccines: Easier Said Than Done).
Realistically, it could take a year or longer before most people could be offered a well-matched pandemic vaccine (and even its effectiveness is unknown).
A study we looked at a couple of weeks ago (see NPJ Vaccines: Modeling the Impact of Early Vaccination in an Influenza Pandemic in the United States) concluded it is better to have a less-well-matched vaccine available early, than a well-matched vaccine late.
While most countries are understandably focused on preparing for a clade 2.3.4.4b H5 pandemic virus , last February the WHO released their latest recommendations for Candidate Vaccine Viruses for Pandemic Preparedness - Feb 2025, which included two new H5 viruses from different clades.
A not so subtle reminder that Nature's laboratory is open 24/7, and is fully capable of generating new and unexpected influenza threats with very little warning.
#18,421
In May of last year we looked at plan by Japan's MOH To Stockpile 10 Million Doses of H5N1 Vaccine, enough to vaccinate about about 8% of their population. The MOH outlined their rationale for this in the following (translated) statement:
HPAIV (H5N1) has not acquired the ability to efficiently transmit from person to person, and is unlikely to lead to a pandemic in humans at this time. Since many cases of infection with HPAIV (H5N1) have been reported, the chances of human exposure to HPAIV (H5N1) are increasing, and there is a high possibility that sporadic cases of human infection will continue to be reported.
Since then, the number of sporadic human infections have increased markedly, as have reports of HPAI H5 infection in a growing array of mammalian species (see USDA H5N1 in Mammalian Wildlife).
A number of other countries, including the UK, Canada, the United States and the EU have also announced plans to stockpile limited quantities of HPAI H5 vaccine. Since these vaccines have a limited shelf life, and these viruses continue to evolve, it is impractical to stockpile large quantities.
But having some quantity of pre-existing vaccine on hand could allow certain high risk individuals (like farmers or HCWs) to be partially protected while an updated vaccine is being developed.
Today Japan's Ministry of Health, Labour & Welfare released an extensive set of documents (all in Japanese) on findings by their Health Sciences Committee's 23rd Subcommittee on New Influenza Measures. First the links, then some (translated) excerpts.
- Roster and committee list ［ PDF format: 79KB ］
- Material 1 About future stockpiling types of pre-pandemic vaccines ［ PDF format: 167KB ］
- Reference 1 For future stockpiling types of pre-pandemic vaccines ［ PDF format: 2.0MB ］
- Reference 2 Highly pathogenic avian influenza virus A ( H5N1 ) Risk assessment and response regarding infection cases ［ PDF format: 1.1MB ］
The risk assessment & response document (below) runs 29 pages, and covers a lot of territory. I've posted excerpts from the summary from the National Institute of Infectious Diseases below (note: machine translations are sometimes syntax-challenged).
[Risk of HPAIV(H5N1) acquiring infectious properties for humans]
• Similarly, although the risk of human infection from mammals is low, there have been an increasing number of reports of mammalian infections overseas, and there have been limited reports of detection of the virus in mammals within Japan. Therefore, people should be careful not to approach mammal carcasses unintentionally.
The CDC says the risk is low (CDC 2024c).
• There have been no reported cases of human infection in Japan to date, and there is no evidence that the virus is more infectious to humans, so the risk of infection for people who have no exposure to birds is low. However, as cases of HPAIV (H5N1) detection in birds continue to be reported in Japan, people should be careful not to approach live birds or bird carcasses carelessly.
(SNIP)
The possibility of a human pandemic is low. However, since the spread of infection in birds has been confirmed worldwide and many cases of infection in mammals have been reported, the opportunities for human exposure to HPAIV(H5N1) are increasing, and sporadic cases of human infection are likely to be reported in the future.
• The frequency of contact between humans and birds or mammals infected with HPAIV(H5N1), the risk of infection, and the spread of the virus from these birds and mammals are important.
Although there is insufficient knowledge to quantitatively estimate the risk that the virus will acquire the ability to efficiently transmit from person to person, it is necessary to continue to monitor the outbreak in animals and conduct risk assessments in a timely manner while avoiding contact between infected animals and humans as much as possible.
• Similarly, although the risk of human infection from mammals is low, there have been an increasing number of reports of mammalian infections overseas, and there have been limited reports of detection of the virus in mammals within Japan. Therefore, people should be careful not to approach mammal carcasses unintentionally.
The CDC says the risk is low (CDC 2024c).
• There have been no reported cases of human infection in Japan to date, and there is no evidence that the virus is more infectious to humans, so the risk of infection for people who have no exposure to birds is low. However, as cases of HPAIV (H5N1) detection in birds continue to be reported in Japan, people should be careful not to approach live birds or bird carcasses carelessly.
(SNIP)
The possibility of a human pandemic is low. However, since the spread of infection in birds has been confirmed worldwide and many cases of infection in mammals have been reported, the opportunities for human exposure to HPAIV(H5N1) are increasing, and sporadic cases of human infection are likely to be reported in the future.
• The frequency of contact between humans and birds or mammals infected with HPAIV(H5N1), the risk of infection, and the spread of the virus from these birds and mammals are important.
Although there is insufficient knowledge to quantitatively estimate the risk that the virus will acquire the ability to efficiently transmit from person to person, it is necessary to continue to monitor the outbreak in animals and conduct risk assessments in a timely manner while avoiding contact between infected animals and humans as much as possible.
The document on Future types of pre-pandemic vaccines to be stockpiled (draft) focuses on a local strain from an infected fox with viral meningoencephalitis and demonstrating virus growth in the upper airway, collected on Hokkaido in 2022.
Worth noting, the CDC remarked last December that the HA of the virus that produced a fatal case in Louisianawas similar to this Japan isolate.
Overall, the hemagglutinin (HA) sequences from the two clinical specimens were closely related to HA sequences detected in other D1.1 genotype viruses, including viruses sequenced from samples collected in November and December 2024 in wild birds and poultry in Louisiana. The HA genes of these viruses also were closely related to the A/Ezo red fox/Hokkaido/1/2022 candidate vaccine virus (CVV) with 2 or 3 amino acid changes detected.
Once again due to its length, I've only produced some excerpts from this CVV report.
The vaccine candidate strains indicated by WHO among the Clade 2.3.4.4b epidemic worldwide are H5N8 A/Astrakhan/3212/2020 (IDCDC-RG71A), H5N6 A/Fujian-Sanyuan/21099/2017 (CNICFJ21099), H5N1 A/chicken/Ghana/AVL-763_21VIR7050-39/2021, A/American w i g e o n / S o u t h C a r o l i n a / 2 2 - 0 0 0 3 4 5 - 0 0 1 / 2 0 2 1 ( I D C D C - RC78 ), A / E z o r e d fox/Hokkaido/1/2022 (NIID-002), A/Jiangsu/NJ210/2023 (CNIC-JSNJ210).
Of these, the only H5N1 vaccine strains that have been confirmed by WHO for safety and antigenicity and are available are A/Ezo red fox/Hokkaido/1/2022 (NIID-002) and A/American wigeon/South Carolina/22-000345-001/2021 (IDCDC-RC78). 3
In addition, to compare the antigenicity of epidemic and vaccine strains, a hemagglutination inhibition test was performed using sera from infected ferrets against A/Ezo red fox/Hokkaido/1/2022 (NIID002) and A/American wigeon/South Carolina/22-000345-001/2021 (IDCDC-RC78). The sera from both strains reacted well with the recent epidemic strain (H5N1), and it was determined that there was no difference in reactivity between the two strains (※).
※ All viruses used in this test belong to Clade 2.3.4.4b.
[Future Stockpiling Policy (Draft)]
[Future Stockpiling Policy (Draft)]
Based on the above considerations, since there is no information on vaccine strains that show superiority over A/Ezo red fox/Hokkaido/1/2022 (NIID-002), how about using A/Ezo red fox/Hokkaido/1/2022 (NIID-002) as the vaccine strain for the pre-pandemic vaccine, as was done last year?
Regarding changes to vaccine strains to be stockpiled from FY2026 onwards, how about prioritizing the collection of vaccine candidate strains of subtypes that are important for crisis management, while continuing to consider the possibility of manufacturing by companies, based on the latest knowledge?
The vaccine strain for the pre-pandemic vaccine to be stockpiled for up to 10 million people (※) will be selected from among the H5 subtypes that have been circulating in recent years, Clade 2.3.4.4b, which has been seen to occur widely and in mammals, and from these, the vaccine strains held by the National Institute of Infectious Diseases will be selected in consideration of the vaccine production schedule. In addition, from the viewpoint of antigenic similarity with the circulating virus strain, A/Ezo red fox/Hokkaido/1/2022 (NIID-002) will be stockpiled this year as well.
The selection of vaccine strains from FY2026 onwards will be considered based on the latest knowledge, including the possibility of production by companies. In addition, the stockpiling policy, including future research, will be reconsidered based on the current status of vaccine research and development.
※ It is assumed that the vaccine will be administered to businesses that perform work related to the provision of medical care or work that contributes to the stability of people's lives and the national economy (pharmaceutical manufacturing, air transportation, food manufacturing, police officers, etc.) that are subject to specific vaccinations.
Regarding changes to vaccine strains to be stockpiled from FY2026 onwards, how about prioritizing the collection of vaccine candidate strains of subtypes that are important for crisis management, while continuing to consider the possibility of manufacturing by companies, based on the latest knowledge?
The vaccine strain for the pre-pandemic vaccine to be stockpiled for up to 10 million people (※) will be selected from among the H5 subtypes that have been circulating in recent years, Clade 2.3.4.4b, which has been seen to occur widely and in mammals, and from these, the vaccine strains held by the National Institute of Infectious Diseases will be selected in consideration of the vaccine production schedule. In addition, from the viewpoint of antigenic similarity with the circulating virus strain, A/Ezo red fox/Hokkaido/1/2022 (NIID-002) will be stockpiled this year as well.
The selection of vaccine strains from FY2026 onwards will be considered based on the latest knowledge, including the possibility of production by companies. In addition, the stockpiling policy, including future research, will be reconsidered based on the current status of vaccine research and development.
※ It is assumed that the vaccine will be administered to businesses that perform work related to the provision of medical care or work that contributes to the stability of people's lives and the national economy (pharmaceutical manufacturing, air transportation, food manufacturing, police officers, etc.) that are subject to specific vaccinations.
Although the risk of seeing an H5N1 pandemic is considered low today, that assessment could easily change, and the risk is considered great enough that governments are spending hundreds of millions of dollars to prepare.
As Maggie Fox explained last fall in SCI AM - A Bird Flu Vaccine Might Come Too Late to Save Us from H5N1, our options during the opening months of any pandemic will be limited. Novel vaccine production could easily take months, and we've seen failures to meet goals or deadlines in the past (see Manufacturing Pandemic Flu Vaccines: Easier Said Than Done).
Realistically, it could take a year or longer before most people could be offered a well-matched pandemic vaccine (and even its effectiveness is unknown).
A study we looked at a couple of weeks ago (see NPJ Vaccines: Modeling the Impact of Early Vaccination in an Influenza Pandemic in the United States) concluded it is better to have a less-well-matched vaccine available early, than a well-matched vaccine late.
While most countries are understandably focused on preparing for a clade 2.3.4.4b H5 pandemic virus , last February the WHO released their latest recommendations for Candidate Vaccine Viruses for Pandemic Preparedness - Feb 2025, which included two new H5 viruses from different clades.
- A/Victoria/149/2024, an H5N1 virus isolated from a child returning to Australia from India (see EID Journal: Influenza A(H5N1) Virus Clade 2.3.2.1a in Traveler Returning to Australia from India, 2024) which we now know to be a new genotype, with contributions from the older clade 2.3.2.1a virus and newer clade 2.3.4.4b viruses.
- And A/Fujian/2/2024, an H5N6 virus belonging to subclade 2.3.4.4h, which raised concerns a year ago when two cases appeared in Fujian Province (see China CDC Weekly: Infection Tracing and Virus Genomic Analysis of Two Cases of Human Infection with Avian Influenza A(H5N6) — Fujian Province, China).
1. A(H5N1)
2. A(H5) non-A(H5N1)
3. A(H7N9)
4. A(H7)
5. A(H9N2)
6. A(H1) variant
7. A(H3N2) variant
8. A(H3N8)
9. A(H10)
2. A(H5) non-A(H5N1)
3. A(H7N9)
4. A(H7)
5. A(H9N2)
6. A(H1) variant
7. A(H3N2) variant
8. A(H3N8)
9. A(H10)
A not so subtle reminder that Nature's laboratory is open 24/7, and is fully capable of generating new and unexpected influenza threats with very little warning.