#Genetic and #antigenic characteristics of #zoonotic #influenza A viruses and development of candidate #vaccine viruses for pandemic preparedness (#WHO, Oct. 31 '25)
September 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 one 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 document summarizes the antigenic and genetic characteristics of recent zoonotic influenza viruses and related viruses circulating in animals{1} that are relevant to CVV updates.
Institutions interested in receiving these CVVs should contact WHO at gisrs-whohq@who.int or the institutions listed in announcements published on the WHO website.{2}
Influenza A(H5)
Since their emergence in 1997, high pathogenicity avian influenza (HPAI) A(H5) viruses of the A/goose/Guangdong/1/96 haemagglutinin (HA) lineage have become enzootic in many countries, have infected wild birds and continue to cause outbreaks in poultry and sporadic human and other mammalian infections across a wide geographic area.
A(H5) HA gene segments have paired with a variety of neuraminidase (NA) subtypes (N1, N2, N3, N4, N5, N6, N8 or N9). These viruses have diversified genetically and antigenically, leading to the need for multiple CVVs. This summary provides updates on the characterization of A/goose/Guangdong/1/96-lineage A(H5) viruses and the status of the development of influenza A(H5) CVVs.
Influenza A(H5) activity from 25 February to 22 September 2025
Since 2003, 17 A(H5), 7 A(H5N8), 93 A(H5N6) and 979 A(H5N1) human infections or detections have been reported.
Since 25 February 2025, 24 human infections with A/goose/Guangdong/1/96-lineage viruses have been reported to WHO.
A/goose/Guangdong/1/96-lineage A(H5) viruses have been detected in both domestic and wild birds with spillover to mammals in many countries (...).
Genetic and antigenic characteristics of influenza A(H5) viruses
Twenty-four new human infections or detections with A/goose/Guangdong/1/96-lineage viruses were reported.
Most infected individuals had recent exposure to birds. The human cases included 4 A(H5N1) clade 2.3.2.1a infections, 2 in Bangladesh and 2 fatal infections in India.
Bangladesh reported additional single A(H5) and A(H5N1) cases where clade designations could not be determined due to lack of sequence data.
The HA of the 2.3.2.1a viruses from Bangladesh and India had up to 1 and 7 amino acid substitutions relative to the A/Victoria/149/2024 CVV, respectively.
Antigenic analyses of the viruses from the human cases are pending, but a genetically related virus from poultry in Bangladesh reacted well to post-infection ferret antisera raised against the A/Victoria/149/2024 CVV.
Two human cases of A(H5N1) clade 2.3.4.4b virus infection were detected; 1 in China in an individual with recent travel history to Viet Nam, and 1 fatal case in Mexico.
The A(H5N1) clade 2.3.4.4b virus from China had an HA with 4 amino acid substitutions relative to the A/Jiangsu/ NJ210/2023 CVV. The virus from the human case in Mexico had an HA with 3 amino acid substitutions
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relative to the A/Astrakhan/3212/2020 and A/Ezo red fox/Hokkaido/1/2022 CVVs, however, 1 of the substitutions added a putative glycosylation site in antigenic site B. Antigenic analyses are pending.
Cambodia reported fifteen human cases of A(H5N1) of which 6 were fatal. Viruses from twelve cases were confirmed as belonging to A(H5N1) clade 2.3.2.1e; clade designations could not be determined for the other 3 due to lack of sequence data.
One human infection with an A(H5N1) clade 2.3.2.1e virus was identified in Viet Nam.
The HAs of the human viruses from Cambodia and Viet Nam had, at most, 4 amino acid differences relative to the A/Cambodia/SVH240441/2024 CVV. Ferret antisera raised against A/Cambodia/SVH240441/2024 and the A/Cambodia/SVH240441/2024 CVV reacted well with virus isolated from the human case detected in Viet Nam but less well with a virus from a Cambodian human case.
Ferret antisera raised against A/duck/Vietnam/NCVD-1584/2012 and the clade 2.3.2.1f A/chicken/ Ghana/20/2015 CVV reacted well with the Cambodian virus. Antigenic characterisation of other viruses isolated from human cases in Cambodia is pending.
A(H5) viruses from birds and non-human mammals belonged to the following clades Clade 2.3.2.1a viruses were detected in poultry and wild birds in Bangladesh and in poultry, wild birds, captive tigers and leopards, and domestic cats in India.
Circulation of viruses with clade 2.3.2.1a HAs in these countries has continued despite the introduction of clade 2.3.4.4b viruses.
The HA of viruses detected in poultry in Bangladesh and India had up to 1 and 5 amino acid substitutions relative to the A/Victoria/149/2024 CVV, respectively. No antigenic data are available for these viruses. Viruses collected in the previous reporting period had HAs genetically similar to either the A/Victoria/149/2024 or A/duck/Bangladesh/17D1012/2018 CVVs and reacted well to post-infection ferret antisera raised against at least 1 of the available clade 2.3.2.1a CVVs.
Clade 2.3.4.4b viruses were detected in birds in Africa, North and South America, Antarctica, Asia and Europe. A(H5N1) viruses circulated in birds in most regions; A(H5N6) viruses were detected in poultry in China; A(H5N5) viruses were detected in Europe and North America; A(H5N8) viruses continued to circulate in Egypt; and A(H5N2) viruses were detected in wild birds in Japan.
Infections in wild and captive mammals have been reported in many countries and the outbreak in dairy cattle continued in the USA.
The HAs of A(H5N1) clade 2.3.4.4b viruses detected in birds in Argentina, Bolivia and Brazil were similar to viruses circulating in the region during previous reporting periods with up to 6 amino acid substitutions relative to the A/American wigeon/South Carolina/22-000345-001/2021 CVV. No antigenic data were available.
Although some heterogeneity was observed, A(H5N1) viruses from birds and mammals in Bangladesh, Japan and the USA and multiple countries in Africa and Europe generally reacted well with post-infection ferret antisera raised against at least 1 of the available clade 2.3.4.4b CVVs; a virus from Crozet Islands and an increasing number of viruses from Egypt reacted less well.
The A(H5N6) and A(H5N1) viruses identified in China had 2 to 14 HA amino acid substitutions relative to clade 2.3.4.4b CVVs and most reacted well with post-infection ferret antisera raised against CVV-like viruses.
The HAs of A(H5N5) viruses detected in Europe and North America were genetically related to viruses detected in previous reporting periods and reacted well to ferret antisera raised against at least 1 of the available clade 2.3.4.4b CVVs.
Clade 2.3.2.1e viruses were detected in poultry in Cambodia, Lao People’s Democratic Republic (Lao PDR) and Viet Nam. The HAs of these viruses were similar to viruses detected in previous periods in the region, with 1 to 9 amino acid substitutions relative to the recommended clade 2.3.2.1e A/Cambodia/ SVH240441/2024 CVV. Antigenic analyses are pending.
Clade 2.3.2.1g viruses were detected in poultry in multiple islands of the Republic of Indonesia. These viruses had HAs genetically similar to those of viruses circulating in the previous reporting period (...). Currently, there is no CVV proposed for this clade. These viruses accumulated many amino acid substitutions when compared to the sequences of CVVs of closely related clades.
Antigenic analyses showed these viruses reacted poorly with post-infection ferret antisera raised against the clade 2.3.2.1e A/duck/Vietnam/ NCVD-1584/2012 and the clade 2.3.2.1a A/duck/Bangladesh/17D1012/2018 CVVs.
Some of the recent Indonesian viruses reacted well to post-infection ferret antiserum raised against the clade 2.3.2.1f A/chicken/ Ghana/20/2015 CVV.
Influenza A(H5) candidate vaccine viruses
Based on current genetic, antigenic and epidemiologic data, no new CVVs are proposed. The available and pending A(H5) CVVs are listed in Table 2.
Influenza A(H9N2)
Influenza A(H9N2) viruses are enzootic in poultry in many parts of Africa, Asia and the Middle East, with the majority of viruses belonging to either the B or G HA lineage.{3}
Since the late 1990s, when the first human infection was identified, sporadic detections of A(H9N2) viruses in humans and pigs have been reported, with associated mild disease in most human cases and no evidence for sustained human-to-human transmission.
Influenza A(H9N2) activity from 25 February to 22 September 2025
Twenty-four human infections with A(H9N2) viruses have been identified in China, 4 with disease onset dates in the previous reporting period.
A(H9N2) viruses were detected in poultry in multiple countries in Africa, Asia and the Middle East and in an illegally imported poultry product in Japan.
Genetic and antigenic characteristics of influenza A(H9N2) viruses
The HAs of the 15 sequenced human viruses belonged to clade B4.7. Fourteen of these viruses belonged to clade B4.7.2 and had up to 25 amino acid substitutions relative to the A/Anhui-Tianjiaan/11086/2022 CVV.
The other human virus had a clade B4.7.4 HA with 14 amino acid substitutions relative to the A/Anhui-Lujiang/39/2018 CVV.
The majority of human viruses tested antigenically reacted well to post-infection ferret antisera raised against the A/Anhui-Tianjiaan/11086/2022 or the A/Anhui-Lujiang/39/2018 CVV.
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A(H9N2) viruses from birds belonged to the following clades: A Clade B4.6 virus was detected in an imported poultry product in Japan. The HA of this virus was genetically similar to viruses previously reported in China, Lao PDR and Singapore. There is currently no CVV for clade B4.6, but the virus reacted well to post-infection ferret antisera raised against both the clade G5.5 A/Oman/2747/2019 and clade B-like A/chicken/Hong Kong/G9/97 CVVs.
Clade B4.7 viruses were detected in poultry in Cambodia and Viet Nam. The HAs of these viruses continued to diversify genetically and accumulated up to 21 amino acid substitutions relative to the A/Anhui-Tianjiaan/11086/2022 CVV. No antigenic data were available from these viruses.
Clade G5.5 viruses were detected in poultry in Israel, Nigeria and Togo. Moreover, viruses belonging to clade G5.5 were identified in poultry in Mauritania and Senegal, although from samples collected in the previous reporting period. The HAs of the viruses from Israel had accumulated 8 amino acid substitutions relative to the A/Oman/2747/2019 CVV. The HAs of viruses from Nigeria, Mauritania, Senegal and Togo were genetically related to viruses circulating in West Africa in the previous period and had up to 12 amino acid substitutions relative to the A/Oman/2747/2019 CVV.
Ferret antiserum raised against the A/Oman/2747/2019 CVV reacted well with a virus from Togo. No antigenic data were available for the other G5.5 viruses.
Clade G5.6 viruses were detected in poultry in Egypt. These viruses had up to 35 amino acid substitutions relative to the A/Oman/2747/2019 CVV. Ferret antisera raised against either the A/Hong Kong/G9/97 or A/Oman/2747/2019 CVVs, however, reacted well with the majority of the viruses tested.
Clade G5.7 viruses were detected in poultry in Bangladesh and India, although from samples collected during the previous reporting period. The HAs of viruses identified in India were genetically related to those circulating during previous reporting periods and had accumulated up to 28 amino acid substitutions relative to the A/Bangladesh/0994/2011 CVV with 8 amino acid substitutions occurring in putative antigenic sites.
Ferret antiserum raised against the A/Bangladesh/0994/2011 CVV reacted well with the majority of Bangladesh viruses tested, however, some viruses with mutations in putative antigenic sites reacted less well.
Clade Y8 viruses were detected in poultry in France and Madagascar, and in wild birds in Europe and North America. The HA sequences of viruses detected in Madagascar were similar to previously reported viruses in the country. The HA sequence of the virus from France was genetically similar to viruses previously reported in Europe. No antigenic data were available for these viruses and there is currently no CVV for this clade.
Influenza A(H9N2) candidate vaccine viruses
Based on the available antigenic, genetic and epidemiologic data, no new CVVs are proposed. The available and pending A(H9N2) CVVs are listed in Table 3.
Influenza A(H10)
A(H10) viruses are frequently detected in poultry in many regions of the world and are considered endemic in poultry in China, with rare human infections reported.
Prior to this reporting period, 4 A(H10N3), 1 A(H10N5) and 3 A(H10N8) human infections were detected in China and A(H10N7) viruses were detected in individuals with conjunctivitis or mild upper respiratory tract symptoms in Australia (n=2) and Egypt (n=2).
Influenza A(H10) activity from 25 February to 22 September 2025
Two human A(H10N3) virus infections were identified in China.
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Antigenic and genetic characteristics of influenza A(H10N3) viruses
One of the human A(H10N3) viruses was sequenced and had an HA that was genetically similar to human A(H10N3) viruses from 2024, maintaining avian virus signatures at key receptor binding sites. As with previous viruses, the recent A(H10N3) virus had some gene segments derived from A(H9N2) viruses. No virus was recovered from the clinical material.
A(H10N3), A(H10N4) and an A(H10N8) virus were detected in ducks and chickens in Fujian and Jiangxi Provinces of China, some with collection dates during the previous reporting period. The HAs of these viruses formed subtype-specific phylogenetic clades with those of the A(H10N3) viruses being genetically similar to the human A(H10N3) viruses.
A(H10N7) viruses, genetically similar to those detected in previous periods, were detected in ducks in Cambodia.
Influenza A(H10N3) candidate vaccine viruses
Based on the available genetic and epidemiologic data, no new CVVs are proposed. The pending A(H10N3) CVV is listed in Table 4.
Influenza A(H1)v{4}
Influenza A(H1) viruses are enzootic in swine populations in most regions of the world. The genetic and antigenic characteristics of the viruses circulating in different regions are diverse. Viruses isolated from human infections with swine influenza A(H1) viruses are designated as A(H1) variant ((H1)v) viruses and have been previously detected in the Americas, Asia and Europe.
Influenza A(H1)v activity from 25 February to 22 September 2025
One case of infection with an A(H1N1)v virus was detected in Germany. Multiple clades of A(H1) viruses were detected in swine populations globally (...).
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Antigenic and genetic characteristics of influenza A(H1N1)v viruses
The A(H1N1)v virus case from Germany was sequenced and had an HA belonging to clade 1C.2.2 similar to other 1C.2.2 viruses detected in swine in the region. The HA had 27 amino acid substitutions compared to the clade 1C.2.2 CVV, A/Hessen/47/2020. No antigenic data were available.
Influenza A(H1)v candidate vaccine viruses
Based on the available antigenic, genetic and epidemiologic data, no new A(H1)v CVVs are proposed. The available and pending A(H1)v CVVs are listed in Table 6.
Influenza A(H3N2)v
Influenza A(H3N2) viruses with diverse genetic and antigenic characteristics are enzootic in swine populations in most regions of the world. Human infections with influenza A(H3N2)v viruses originating from swine have been previously documented in the Americas, Asia, Australia and Europe.
Influenza A(H3N2)v activity from 25 February to 22 September 2025
No cases of infection with A(H3N2)v viruses were detected in this reporting period. A(H3N2) viruses were detected in swine in Canada, France, Italy, Portugal, Russian Federation and the USA (Table 7).
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Influenza A(H3N2)v candidate vaccine viruses
Based on the available antigenic, genetic and epidemiologic data, no new CVVs are proposed. The available A(H3N2)v CVVs are listed in Table 8
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Acknowledgements
Acknowledgement goes to the WHO Global Influenza Surveillance and Response System (GISRS) which provides the mechanism for detection and monitoring of zoonotic influenza viruses. We thank the National Influenza Centres of GISRS who contributed information, clinical specimens and viruses, and associated data; WHO collaborating centres of GISRS for their in-depth characterisation and analysis of viruses and preparation of CVVs; WHO Essential Regulatory Laboratories of GISRS; and WHO H5 Reference Laboratories for their complementary analyses and preparation of CVVs. We acknowledge the WOAH/FAO Network of Expertise on Animal Influenza (OFFLU) laboratories for their in-depth characterization and comprehensive analysis of viruses and other national public and veterinary health institutions for contributing information and viruses. We also acknowledge the GISAID Global Data Science Initiative for the EpiFluTM database, and other sequence databases which were used to share gene sequences and associated information.
{1} For information relevant to other notifiable influenza virus infections in animals refer to https://wahis.woah.org/#/home
{3} See https://wwwnc.cdc.gov/eid/article/30/8/23-1176_article
{4} Standardization of terminology for the influenza virus variants infecting humans: Update (https://cdn.who.int/media/docs/default-source/influenza/global-influenza-surveillance-and-response-system/nomenclature/standardization_of_terminology_influenza_virus_variants_update.pdf?sfvrsn=d201f1d5_6).
Source: World Health Organization, Weekly Epidemiological Record (WER), https://iris.who.int/server/api/core/bitstreams/af989289-7535-4a61-89b9-5db72aa5e829/content
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