Porcine #influenza #mAbs to #H3, #H5, and #H7 hemagglutinins recognize H3 egg adapted site and target the HA stem

 

Abstract

Introduction

Monoclonal antibodies (mAbs) are critical tools for elucidating viral evolution, informing vaccine design, and developing antiviral therapeutics. Large-animal models, such as the pig, that closely mirror human immune responses are essential for understanding influenza immunity.

Methods

Pigs were either infected or sequentially immunized with influenza viruses and monoclonal antibodies directed against H3, H5, and H7 influenza virus haemagglutinins were isolated. Antibody specificity, breadth, epitope targeting (head versus stem), neutralizing capacity, and Fc-mediated activity were assessed across influenza subtypes.

Results

Pigs generated both strain-specific and broadly reactive mAbs targeting haemagglutinin head and stem epitopes. An H3-specific mAb (H3–57) selectively recognized the egg-adapted L194P mutation associated with reduced human vaccine effectiveness. H5 and H7 immunization induced neutralizing antibodies, including cross-group stem mAbs reactive with H1, H3, and H5 haemagglutinins. Fc-mediated activity correlated with antibody binding strength rather than epitope location.

Conclusions

These findings demonstrate that pigs mount antibody responses closely resembling those observed in humans, including recognition of conserved stem epitopes and adaptive head mutations. Porcine mAbs represent powerful new tools for dissecting influenza immunity, guiding vaccine design, and enhancing pandemic preparedness using a physiologically relevant large-animal model.

Source: 

Link: https://academic.oup.com/discovimmunology/article/5/1/kyag006/8503709

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Host-specific functional #evolution of #seal #influenza A virus #NS1 protein following #avian-to-seal #transmission

 

ABSTRACT

Marine mammals, particularly seals, are susceptible to both avian and human influenza A viruses (IAVs), making them potential intermediates for zoonotic virus emergence. In recent decades, repeated transmissions of avian influenza viruses (AIVs) from wild aquatic birds, their natural reservoir, have caused significant mortality in seals. Defining the molecular determinants of viral adaptation in marine mammals, and their implications for replication in human cells, is therefore essential. The non-structural protein 1 (NS1) of AIV, a key antagonist of the interferon (IFN) response, plays a central role in host adaptation. Here, we analyzed NS1 proteins from seal influenza viruses (H3, H4, H5, H7, and H10 subtypes) and their closest avian relatives isolated between 1980 and 2023, and evaluated their function in seal, avian, and human cells. Phylogenetic analysis confirmed multiple bird-to-seal transmission events. Seal-derived NS1 proteins generally contained few strain-specific amino acid substitutions and showed comparable expression and IFN antagonism to their avian precursors. A notable exception was the seal H10N7 virus isolated in 2014 in Northeastern Europe, which harbored three previously uncharacterized substitutions at NS1 amino acid residues 94, 104, and 171. These amino acid substitutions markedly altered NS1 properties to enhance protein stability, suppress IFN induction, mediate host transcription shut-off, and increase polymerase activity in human cells, without affecting NS1 expression or reducing virus replication in avian cells. Overall, these results reveal how NS1 undergoes host-specific functional evolution following avian-to-seal transmission and provide mechanistic insight into the adaptation of influenza A viruses to mammalian hosts.

IMPORTANCE

Avian influenza viruses (AIVs) circulate naturally in wild aquatic birds but occasionally infect mammals, including seals, where they can cause severe outbreaks. Seals are of particular concern because they can harbor both avian and human influenza viruses, creating opportunities for reassortment and the emergence of novel zoonotic strains. Understanding how AIVs adapt to mammalian hosts is therefore critical for anticipating and mitigating future influenza threats. Here, we investigated the role of the NS1 protein, a key viral factor that suppresses host immune responses, in seal-derived AIVs. Overall, NS1 expression and function were conserved across different subtypes and host cells. However, we identified unique amino acid substitutions in the NS1 of a seal H10N7 virus that enhanced protein stability, interferon antagonism, and viral adaptation in human cells. These findings illustrate how minor changes in NS1 protein can drive host adaptation and underscore the need for continued surveillance of AIVs in seals.

Source: 

Link: https://journals.asm.org/doi/full/10.1128/jvi.01650-25?af=R

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#Argentina - #Influenza A #H5 viruses of high pathogenicity (Inf. with) (non-poultry including wild birds) (2017-) - Immediate notification

 

{A Coscoroba Swan. By Charles J. Sharp - Own work, from Sharp Photography, sharpphotography.co.uk, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=179069673}

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{A Black-Necked Swan. By Charles J. Sharp - Own work, from Sharp Photography, sharpphotography.co.uk, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=178158764}

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{A Fulvous Whistling Duck. By JeffreyGammon - Own work, CC BY 4.0, https://commons.wikimedia.org/w/index.php?curid=158156460}

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{A Brown-Hooded Gull. By Charles J. Sharp - Own work, from Sharp Photography, sharpphotography.co.uk, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=179073441}

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Contact with wild migratory birds present in the area is presumed to be the likely source of infection. Virological analysis has identified the presence of the H5 subtype of high pathogenicity avian influenza (HPAI). The determination of the neuraminidase subtype is pending in order to complete the characterisation of the pathogenic agent. Further information is provided in the epidemiological comments of the outbreak.

Source: 

Link: https://wahis.woah.org/#/in-review/7291

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#Argentina - High pathogenicity avian #influenza #H5 viruses (Inf. with) (#poultry) - Immediate notification

 

At a heavy breeding poultry farm located in the province of Buenos Aires, an increase in mortality and the presence of clinical signs consistent with high pathogenicity avian influenza (HPAI) were observed. Given the clinical suspicion, official intervention was carried out, including a health inspection and the collection of diagnostic samples for processing. Laboratory analyses confirmed a positive result for high pathogenicity avian influenza subtype H5 (HPAI H5).

The event occured on a farm raising heavy breeding stock. On 21/02/2026, the National Service of Agri-Food Health and Quality (SENASA) received a notification concerning mortality and clinical signs consistent with high pathogenicity avian influenza (HPAI) which began on 19/02/2026, as reported by the reporting person. On 22/02/2026, the suspicion was officially addressed with the restriction of the establishment and taking of samples for official diagnosis. On 23/02/2026, the samples tested positive for HPAI H5. All the birds on the establishment will be culled. We will update the population data in subsequent follow-up reports.

Source: 

Link: https://wahis.woah.org/#/in-review/7290

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#Philippines - High pathogenicity avian #influenza #H5 viruses (#poultry) (Inf. with) - Immediate notification

 

Affected avian species were grazing ducks in Davao del Sur Region.

Source: 

Link: https://wahis.woah.org/#/in-review/7105

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#Finland - #Influenza A #H5 viruses of high pathogenicity (Inf. with) (non-poultry including wild birds) (2017-) - Immediate notification [FINAL]

 

A Whooper Swan in Lounais-Suomen aluehallintovirasto Region.

Source: 

Link: https://wahis.woah.org/#/in-review/7156

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#Italy - #Influenza A #H5 viruses of high pathogenicity (Inf. with) (non-poultry including wild birds) (2017-) - Immediate notification

 

{Eurasian Teal}

{Eurasian Wigeon}

{Mute Swan}

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This is a new event opened to report outbreaks for which the N subtype could not be determined due to insufficient diagnostic material; in these cases, only the presence of H5 can be confirmed.

Three Common Teals (Friuli Venezia Giulia, Lombardy) , two Eurasian Wigeons (Friuli Venezia Giulia), one Mute Swan (Lombardy). 

Source: 

Link: https://wahis.woah.org/#/in-review/7144

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Isolation and subtyping of avian #influenza A virus from wild #birds in #Khartoum, #Sudan

 

Abstract

Avian influenza (AI) is a significant disease affecting chickens and other avian species. Wild birds are thought to contribute to the virus transmission. The present study intends to explore the existence of AI type A virus in wild birds at the Six April Zoo, Khartoum State, Sudan. A total of 42 cloacal and tracheal swabs were collected from clinically healthy individuals belonging to five different wild bird species. The selected wild bird species were Common crane Grus grus, Sudan crowned crane Balearica pavonina, Helmeted guinea fowl Numida meleagris, Duck sp. Anatidae and Chestnut-billed sand grouse Pterocles exustus. Swabs were examined for AI virus antigen using the agar gel immunodiffusion (AGID) test, and all tested swabs produced positive results. The swab samples were inoculated into embryonated chicken eggs. The isolated virus was identified by AGID test and polymerase chain reaction. The virus was isolated from swabs collected from Grus grus, Balearica pavonina, Numida meleagris, Duck sp. Anatidae and Pterocles exustus. Subtyping of the isolated viruses was performed using reverse transcriptase-polymerase chain reaction, which identified the H5 subtype.

Source: 

Link: https://ojvr.org/index.php/ojvr/article/view/2228

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#Kazakhstan - #Influenza A #H5 viruses of high pathogenicity (Inf. with) (non-poultry including wild birds) (2017-) - Immediate notification [FINAL]

{Greylag Goose}

{Mallards}

A Greylag Goose, two Mallards  in Aqmola Region.

Source: 

Link: https://wahis.woah.org/#/in-review/7093

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#Spain - #Influenza A #H5 viruses of high pathogenicity (Inf. with) (non-poultry including wild birds) (2017-) - Immediate notification

 

{By Pierre Dalous - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=29066936}

This event will collect the detections made by sampling carried out in 2025.

Report (LNR): 2025/005921 B. A vulture (Gyps fulvus) collected at Quintanas de Valdelucio.

Source: 

Link: https://wahis.woah.org/#/in-review/7077

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#USA, #Influenza A #H5: #Situation #summary of confirmed and probable #human cases since 2024 (as of Nov. 25 '25)

 

{Summary}

Confirmed Cases at National Level

[National - Total Cases: 71 {+1}{§}]

[Cases - Exposure Source]

-- 41 - Dairy Herds (Cattle){*}

-- 24 - Poultry Farms and Culling Operations{*}

-- 3 - Other Animal Exposure{†}

-- 3 - Exposure Source Unknown{‡}

Probable Cases at National Level

[National - Total Cases: 7 {no change}]

[Cases - Exposure Source]

-- 1 - Dairy Herds (Cattle){*}

-- 5 - Poultry Farms and Culling Operations{*}

-- 0 - Other Animal Exposure{†}

-- 1 - Exposure Source Unknown{‡}

NOTE: One additional case was previously detected in a poultry worker in Colorado in 2022. Louisiana reported the first H5 bird flu death in the U.S.

{*} Exposure Associated with Commercial Agriculture and Related Operations

{†} Exposure was related to other animals such as backyard flocks, wild birds, or other mammals

{‡} Exposure source was not able to be identified

(...)

{§} A case from Washington State, see more at: https://doh.wa.gov/newsroom/grays-harbor-county-resident-dies-complications-avian-influenza

Source: 

Link: https://www.cdc.gov/bird-flu/situation-summary/?CDC_AAref_Val=https%3A%2F%2Fwww.cdc.gov%2Fflu%2Favianflu%2Favian-flu-summary.htm&cove-tab=1

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#Portugal - High pathogenicity avian #influenza #H5 viruses (#poultry) (Inf. with) - Immediate notification

 

{Porto Region}

Small farm keeping 197 mixed species poultry and 187 captive birds of exotic species.

Source: WOAH, https://wahis.woah.org/#/in-review/7015

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#Cambodia notified two additional #human cases of infection with #influenza #H5N1, #Bangladesh one case of #H5, #China four cases of #H9N2 (HK CHP, Nov. 21 '25)

{Excerpt}

This Week:

[Date of report - Country - Province / Region District / City - Sex - Age - Condition at time of reporting  - Subtype of virus]

1) .../10/2025 - Cambodia - Takeo Province - F - 14 - Hospitalised - H5N1 

2) 16/10/2025 - Cambodia - Kampong Speu Province - F - 3 - Under intensive care - H5N1

(...)

[Place of occurrence - No. of cases  (No. of deaths) - Details]

-- Bangladesh - 1(0) 

- Avian influenza A(H5): 

1) Sylhet Division: A boy with onset on July 27, 2025. 

-- Chinese Mainland - 4(0) 

- Avian influenza A(H9N2): 

- Guangdong Province: 

1) An individual with onset in February 2025. The case was retrospectively reported. 

- Guangxi Zhuang Autonomous Region: 

2, 3) Two individuals with onset in February 2025. Both cases were retrospectively reported.  

- Tianjin Municipality: 

4) An individual with onset in February 2025. The case was retrospectively reported. 

-- Mexico - 1(0) 

- Avian influenza A(H5): 

1) Mexico City: A 23-year-old woman with onset on September 14, 2025. 

(...)

Source: Centre for Health Protection, Hong Kong PRC SAR, https://www.chp.gov.hk/files/pdf/2025_avian_influenza_report_vol21_wk42.pdf

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#Iceland - #Influenza A #H5 viruses of high pathogenicity (Inf. with) (non-poultry including wild birds) (2017-) - Immediate notification

 

{[Common Raven] By Accipiter (R. Altenkamp, Berlin) - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=6806927}

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Note 16/10/2025: The case reported in this event was confirmed to be H5 but was negative for N1 and N5. Therefore, it is assumed that a new serotype has been detected in the country.

The raven was found sick with a broken wing, emaciated and with diarrhea. It was euthanized.

Source: WOAH, https://wahis.woah.org/#/in-review/6868

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Divergent #antibody-mediated #population #immunity to #H5, #H7 and #H9 subtype potential #pandemic #influenza viruses

 

Abstract

Influenza continues to cause significant mortality globally and possesses substantial pandemic potential. Assessing pandemic risk requires a clear understanding of existing population immunity. Leveraging a unique large-scale cohort of human sera, we evaluated total and neutralising antibody-mediated immunity to multiple haemagglutinin (HA) proteins, including those from subtypes with high pandemic potential. Our analysis reveals that population immunity is heterogeneous, with distinct age-dependent differences in responses to H5, H7, and H9 avian influenza subtypes. These shifts align with historical circulation patterns of seasonal H1N1 and H3N2 human viruses. Notably, H7 viruses are primarily neutralised through head domain epitopes, while H5 viruses are targeted mainly via stem epitopes, although in both instances some neutralisation occurred via receptor binding site-adjacent epitopes. Furthermore, H7 responses were dominated by non-glycan-targeted IgG2 antibodies, whereas H5 responses were primarily IgG1-mediated. These findings highlight varying levels of susceptibility to influenza across the population, supporting vaccination approaches informed by exposure history.

Competing Interest Statement

CPT has received lecture fees from Moderna.

Funding Statement

J.S.B. was supported by funding from the Biotechnology and Biological Sciences Research Council (BBSRC) doctoral training programme grant [grant number BB/M011224/1]. R.S. is funded by a Medical Research Council Impact Accelerator Account grant [grant ref MR/X502674/1]. RG was funded by The Institute for Global Pandemic Planning at the University of Warwick, UK, as part of a philanthropically supported doctoral programme. K.C. was funded via the Medical Research Council doctoral training programme grant [MC_UP_A025_1011]. L.H. was funded by a Defence and Science Technology Laboratory grant [grant ref RQ31692]. U.O. and C.P.T. acknowledge funding from the British Council ISFP scheme [grant number 47650215]. N.C.R. is supported by a Royal Society Dorothy Hodgkin Research Fellowship [grant number DHR00620].

Source: MedRxIV, https://www.medrxiv.org/content/10.1101/2025.09.08.25335309v1

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