#Baloxavir and #molnupiravir protect against severe #influenza #H5N1 #infection in immunosuppressed hamsters

 

Abstract

Highly pathogenic avian influenza A(H5N1) viruses continue to expand their geographic and host range, raising concerns about zoonotic transmission and pandemic preparedness. Immunocompromised individuals often develop severe and prolonged disease, yet evidence guiding antiviral therapy remains limited. Here, we characterized the pathogenesis and assessed direct-contact transmission of an influenza A(H5N1) clade 2.3.4.4b genotype D1.1 virus recently isolated from a human case in British Columbia, Canada, in cyclophosphamide-immunosuppressed hamsters, with normal hamsters included for comparison of infection outcomes and viral shedding kinetics. We also evaluated the antiviral efficacy of oseltamivir (20 mg/kg twice daily for 5 days), baloxavir (50 mg/kg, 2 doses), and molnupiravir (50 or 200 mg/kg twice daily) as monotherapies or in combination (oseltamivir with low-dose molnupiravir) in immunosuppressed hamsters. While normal hamsters showed no mortality and achieved viral clearance, infection in immunosuppressed hamsters caused severe disease characterized by prolonged viral replication, neuroinvasion, and 75% mortality, with no direct-contact transmission detected. In the antiviral efficacy experiment, placebo-treated hamsters exhibited 50% mortality. Baloxavir resulted in 100% survival, shortened viral shedding, reduced viral replication and pulmonary inflammatory responses, and prevented neuroinvasion. High-dose molnupiravir also prevented mortality and achieved viral clearance in lung and brain tissues. Combination therapy resulted in 75% survival and similarly achieved viral clearance in both tissues, with reduced morbidity compared with oseltamivir and low-dose molnupiravir monotherapies. Oseltamivir resulted in 75% survival but failed to prevent severe clinical signs or reduce tissue viral titers, whereas low-dose molnupiravir showed outcomes comparable to placebo. These findings demonstrate the high pathogenicity of a human A(H5N1) isolate in immunosuppressed hamsters, support baloxavir as an effective therapeutic option, and identify molnupiravir-based regimens as promising strategies for severe influenza A(H5N1) infection.

Source: PLoS Pathogens, https://doi.org/10.1371/journal.ppat.1014796

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#Netherlands, Avian #influenza confirmed in One Additional #Poultry #Farm in Hierden (Min. Agriculture, Nov. 11 '26)

 

{Extract}

    Bird flu has been detected again in Hierden (municipality of Harderwijk, province of Gelderland). 

    This time, the infection occurs at a duck breeding farm. 

    To prevent the spread of the virus, the Ministry of Agriculture, Fisheries, Food Security and Nature (LVVN) has decided to have the approximately 9,500 animals at the location culled by the Netherlands Food and Consumer Product Safety Authority (NVWA). 

    This farm in Hierden has been culled three times previously due to a bird flu infection: twice in 2022 and once in 2025. 

    On November 9, another bird flu infection was also detected at a poultry farm with ducks in Hierden; this farm has since been culled.

(...)

Source: Netherlands' Ministry of Agriculture, https://www.rijksoverheid.nl/actueel/nieuws/2026/11/11/vogelgriep-vastgesteld-in-hierden

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#Maternal and perinatal #outcomes in pregnant women with #Lassa fever: analysis from the LASCOPE prospective cohort study

 

Summary

Background

Lassa fever, a viral haemorrhagic fever endemic in west Africa, is usually described as associated with severe maternal and perinatal outcomes. Previous studies reported maternal mortality of 33% (whereas overall mortality is about 14% in Nigeria for patients admitted to hospital) and fetal mortality is up to 60%. However, most evidence derives from small case series with substantial limitations. We aimed to assess maternal death and perinatal outcomes in a prospective cohort study with standardised medical care protocols.

Methods

We analysed data from the LASCOPE cohort from the Federal Medical Centre Owo, Nigeria, which included all patients with PCR-confirmed Lassa fever. In this analysis, non-pregnant women of childbearing age (15–45 years) were compared with pregnant women, defined as having an ongoing pregnancy during Lassa fever. The primary maternal outcome was all-cause mortality 28 days after admission and the primary pregnancy outcome was fetal death. Mortality at 28 days was compared using Kaplan–Meier estimates and a Cox proportional-hazards model, the cumulative incidence of fetal death was estimated with livebirth as a competing event, and the association between gestational age at symptom onset and fetal death was assessed by logistic regression.

Findings

Between April 4, 2018, and Feb 18, 2023, of 1006 patients in the LASCOPE cohort admitted with PCR-confirmed Lassa fever, 703 were excluded for not being of childbearing age, and 303 were women of childbearing age, of whom 45 were pregnant. The median age of pregnant women was 28 years (IQR 24–32). The 28-day mortality was comparable between pregnant and non-pregnant women (four [9%; 95% CI 2–21] of 45 vs 19 [7%; 95% CI 4–11] of 258; hazard ratio 1·19 [95% CI 0·41–3·50]; log-rank p=0·75). Fetal case-fatality rate was 60% (27 of 45), with higher risk of fetal death if infection occurred early in the pregnancy (100% for the first trimester, 82% for the second trimester, and 25% for the third trimester). Each additional week of gestation at symptom onset was associated with a reduction in the odds of fetal death (odds ratio 0·77 [95% CI 0·61–0·90]). Among 15 liveborn infants, three (20%) died within 30 days.

Interpretation

Although the fetal prognosis was poor, as previously reported, maternal fatality was lower than previously indicated, potentially reflecting improved supportive care and patient monitoring. These findings suggest that maternal mortality might be lower than historically reported, while confirming the urgent need for specific therapeutic interventions to improve fetal outcomes.

Funding

INSERM/REACTing; the African Coalition for Epidemic Research, Response and Training consortium; the University of Oxford; the UK Department for International Development; the Wellcome Trust; the French Ministry of Foreign Affairs; the Agence Nationale de Recherches sur le SIDA et les hépatites virales; and the French National Research Institute for Sustainable Development.

Source: The Lancet Infectious Diseases, https://doi.org/10.1016/S1473-3099(26)00524-4

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#Netherlands, Avian #influenza confirmed in Hierden Duck #Farm (Min. Agriculture, Nov. 11 '26)

 

{Extract}

News item | 09-11-2026 | 21:09

    Bird flu has been detected at a meat duck farm in Hierden (municipality of Harderwijk, province of Gelderland). 

    To prevent the spread of the virus, the Ministry of Agriculture, Fisheries, Food Security and Nature (LVVN) has decided to have the approximately 70,000 animals at the location culled by the Netherlands Food and Consumer Product Safety Authority (NVWA). 

    This farm in Hierden was previously culled twice in 2022 due to a bird flu outbreak.

    A restriction zone of 10 kilometers is established, consisting of a protection zone with a radius of 3 kilometers and a surveillance zone of 10 kilometers. 

    There are 2 poultry farms located in the 1-kilometer zone surrounding this contaminated location. 

    There are no other poultry farms in the 3-kilometer zone. There are 11 other poultry farms in the 10-kilometer zone.

    A transport ban applies immediately to the entire 10-kilometer zone. This means that no birds, hatching eggs, and/or consumption eggs may be transported from locations with birds in this zone. 

    A ban also applies to the disposal of bird manure and used bedding. These measures are necessary to prevent the spread to other parts of the country. Animals other than birds and their products may be transported to and from locations with birds, provided this is done in accordance with the strict conditions of the hygiene protocol.

    The location of the 10-kilometer zone can be seen on  the animal disease viewer of the Netherlands Enterprise Agency (RVO).

(...)

Source: Netherlands' Ministry of Agriculture, https://www.rijksoverheid.nl/actueel/nieuws/2026/11/09/vogelgriep-vastgesteld-in-hierden

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#Australia, #H5 avian #influenza events in #wildlife (Dept. of Agriculture, Nov. 11 '26)

 

{Extract}

(...)

Event data

    As of 4pm AEST, 10 November 2026, Australia has 738 confirmed events of H5 bird flu in wildlife.

        § 10 in Western Australia (WA)

        § 342 in South Australia (SA)

        § 81 in New South Wales (NSW)

        § 2 in Queensland (QLD)

        § 249 in Victoria (VIC)

        § 53 in Tasmania (TAS)^

        § 1 in Other Territories#

    {^} Includes events on Macquarie Island

    {#} Jervis Bay Territory (Commonwealth jurisdiction)

(...)

Source: Australian Department of Health, https://www.agriculture.gov.au/campaigns/birdflu/latest-data#h1_bird_flu

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#Japan - #Influenza A #H5N1 viruses of high pathogenicity (Inf. with) (non-poultry including wild birds) (2017-) - Immediate notification

 

{Extract}

(...)

A Wild Whooper Swan in the Hokkaido Region.

A Wild Large-Billed Crow in the Akita Region.

(...)

Source: World Animal Health Organization, https://wahis.woah.org/#/in-review/7940

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#Transmission #dynamics of #Nipah virus in #Bangladesh and India, 2001–2026: Systematic review and inference on reproduction number, offspring dispersion, and serial interval

 

Abstract

Background

Nipah virus (NiV) is a priority zoonotic pathogen causing high-fatality outbreaks. Early NiV outbreaks in Malaysia and Singapore had limited transmission beyond spillover events. However, since 2001, NiV outbreaks with person-to-person transmission have occurred in Bangladesh and India, driven by the NiV-Bangladesh genotype and NiV-India genotype. Our study aims to estimate the reproduction number, offspring dispersion, and serial interval governing NiV transmission in Bangladesh and India during 2001–2026.

Methods

We conducted a systematic review of NiV outbreak investigations in Bangladesh and India, searching PubMed, Embase, Web of Science, and grey literature through 28 February 2026. Case-level offspring counts from 27 sources (323 cases across 67 outbreaks) were used as input to a hierarchical Bayesian negative binomial offspring distribution model. The serial interval was estimated by parametric distribution fitting to 137 transmission pairs. We conducted country-specific analysis and performed sensitivity analyses to evaluate the robustness of estimates.

Results

Pooling across 67 outbreaks, we estimated a median reproduction number of 0.43 (95% CrI: 0.26–0.75), an offspring dispersion parameter of 0.04 (0.03–0.06), and a serial interval of 13.3 days (95% CI: 12.8–13.8). Country-specific median reproduction numbers were 0.47 (0.22–0.98) for India and 0.35 (0.19–0.63) for Bangladesh, and dispersion parameters were 0.03 (0.02–0.06) and 0.05 (0.03–0.09), respectively, indicating marked overdispersion in both settings.

Conclusion

NiV transmission is self-limiting on average and highly overdispersed, suggesting that a disproportionate share of onward transmission arises from a small number of cases. This epidemiological profile supports targeted containment measures, including contact tracing and quarantine, for effective NiV outbreak control.

Source: Plos Neglected Tropical Diseases, https://doi.org/10.1371/journal.pntd.0014876

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Cross #Protection against #Influenza #H5 Clade 2.3.4.4b Viruses after #H1N1pdm09 Infection

 

Abstract

We challenged ferrets previously infected with influenza A(H1N1)pdm09 virus with H5N1 or H5N5 clade 2.3.4.4b viruses to assess cross-protection. Results show that previous A(H1N1)pdm09 virus immunity conferred partial protection against both viruses, with slightly reduced protection against H5N5 compared with H5N1, potentially reflecting the absence of cross-reactive N5 neuraminidase antibodies.

Source: Emerging Infectious Diseases Journal, https://doi.org/10.3201/eid3212.261032

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#Bundibugyo Virus Disease #Outbreak in #DRC, #Kenya, #Nigeria - Weekly Report No. 25, Data as of 7 November 2026 (WHO, summary): 10,920 cases & 5,323 deaths in DRC

 

{Summary}

{Click on Image to Enlarge}

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Event description

    The Bundibugyo virus disease (BVD) outbreak in the Democratic Republic  of the Congo continues at a high, sustained level of transmission, with no sign of decline: close to 390 confirmed cases were added during the reporting  period and the national seven-day average has stayed between 65 and 67 cases per day. 

    Nord-Kivu now contributes almost as many cases as Ituri and accounts for the  entire increase observed over the last 21 days, while contact follow-up fell to  its lowest level in weeks at the end of the period. 

    The importation events in Kenya and Nigeria remain contained: no new case has been reported in Kenya since 19 October, six of the seven surviving  patients have been discharged and the last contacts will complete monitoring on  11 November, while no secondary case has been identified in Nigeria, where contact monitoring is expected to end on 13 November. 

    In the Democratic Republic of the Congo, insecurity in Beni health zone in  North Kivu and Bafwasende in Tshopo, health-worker strikes in Bas-Uélé and  Tshopo and the continued suspension of response activities in Bafwasende  constrain surveillance and response operations. 

Democratic Republic of the Congo

    As of 7 November 2026, the BVD outbreak in the Democratic Republic of the Congo has affected 67 health zones and 247 health areas across eight provinces; no new health zone was affected during the reporting period. 

    Since  External Situation Report #24, an additional 388 confirmed cases and 197 confirmed deaths have been reported, bringing the cumulative total to 10 920 confirmed cases, including 5 323 confirmed deaths [crude case fatality ratio (CFR) 48.7%].

    Transmission remains highly heterogeneous across affected areas. Ituri  continues to account for the largest proportion of cumulative confirmed cases  (69.7%), although its relative contribution is declining, while Nord-Kivu (24.7% of  cumulative cases; CFR 54.8%) accounted for 46.1% of the cases reported  since the previous report, almost as many as Ituri (47.2%). 

    Transmission persists at lower levels in Haut-Uélé (4.9% of new cases),  Tshopo and Nord-Ubangi. 

    National daily incidence rose steadily from May to its highest levels in late July and mid-August, declined through late September and has fluctuated at  a high plateau since early October. 

    The seven-day moving average ranged between 65 and 67 confirmed cases  per day during the reporting period (64.7 on 7 November, compared with 67.0 on  1 November and a late-October high of 76), still well below the mid-August peak  of 94. 

    Provincial trends continue to diverge. Ituri continues its slow decline from  the late-July peak (seven-day average of 29 cases per day on 7 November, down  from 31 on 1 November and 38 on 19 October), while Nord-Kivu has risen to 31  cases per day (up from 30 on 1 November and 26 on 19 October) and exceeded  Ituri on several days of the period. Haut-Uélé remains stable at three to four cases per day, Tshopo reports sporadic cases (last case on 5 November) and Nord- Ubangi reported three further cases in Yakoma and Wapinda. Bas-Uélé, Sud-Kivu and Sud-Ubangi have reported no case in the last 21 days (Figures 1 and 2).

{Click on Image to Enlarge}

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(...)

Kenya

    Since the previous report, Kenya has reported no new confirmed case of BVD. The cumulative total remains nine confirmed cases, including two deaths  (CFR 22.2%): the imported index case, who died on 5 October, and a 65-year-old family member who died on 23 October. 

    All eight secondary cases (four family members and four hospital staff)  belong to a single known chain of transmission, were epidemiologically linked to  the index case and were already under quarantine when they developed symptoms; no community spread has been detected. 

    The last confirmed case was reported on 19 October 2026. 

    On 6 November, day 32 since the first case was confirmed, the Ministry of  Health announced that a sixth patient had recovered and was being discharged  after testing negative and meeting all discharge criteria.; only one patient remains  under care and continues to be closely monitored. 

    The 42-day countdown to the end of the outbreak will start once this last  patient has recovered and been discharged.

    Of the nine confirmed cases, seven were male and two were female, with  ages ranging from 24 to 65 years. Designated isolation facilities have 211 isolation  beds (scalable to 241).

    A total of 135 contacts have been listed since the index case was  confirmed, comprising 46 airport staff, 45 hospital staff, 26 passengers, 14  relatives and four flight crew members. Of these, eight (5.9%) tested positive  for BVD during quarantine (four relatives and four hospital staff), one of  whom has died.

    Of the remaining 118 contacts, 66 had completed their 21 days of  monitoring and returned home by 6 November and the remaining 52 are expected  to complete quarantine by 11 November 2026.

(...)

Nigeria

    Nigeria has reported a single confirmed case of BVD, announced by the  Federal Ministry of Health on 20 October 2026 in the Federal Capital Territory,  Abuja. 

    The case, a 42-year-old woman, arrived in Abuja from Uganda via Addis  Ababa on 3 October, developed symptoms on 7 October and was admitted to a  private health facility on 11 October; the Nigeria Centre for Disease Control and  Prevention (NCDC) was notified on 19 October and the National Reference  Laboratory confirmed the infection on 20 October. The patient was clinically stable  and, at the request of her country and with clearance from the Nigerian  authorities, was medically evacuated to Switzerland on 26 October 2026,  where she remains in isolation and under medical care in Geneva. 

    No additional confirmed case has been reported. As of 5 November 2026, a  cumulative 62 contacts linked to the index case had been identified,  categorized and followed up; none had developed symptoms, no new contact had  been identified, and seven contacts had completed the mandatory 21-day follow- up and left the quarantine facility, with the remaining contacts due to complete  follow-up on a staggered basis between 31 October and 13 November 2026. 

    Exposure remains confined to a single epidemiological cluster directly linked  to the index case. The 12-day interval between symptom onset and notification,  eight days of which were spent in private-facility care, remains the main concern for undetected exposures.

(...)

Situation interpretation

    The BVD outbreak remains at a critical juncture. In the Democratic  Republic of the Congo, transmission is not declining: close to 390 confirmed cases  and 200 deaths were added in one week, the national seven-day average has held  between 65 and 76 cases per day for five weeks, and the epicentre  continues to shift towards Nord-Kivu, which accounted for the entire 21-day  increase in cases (513 to 661) and deaths (250 to 322) and now reports as many  cases as Ituri each day. Beni, Mutwanga, Oicha, Mabalako and Kalunguta are the  health zones where transmission is intensifying most. At the same time, the  performance of the response weakened at the end of the period: contact follow-up  fell to 69.8% on 7 November, safe burial completion dropped to 85%, refusals  increased, and only half of investigated suspected cases are isolated within 24  hours. Insecurity in Beni, the suspension of activities in Bafwasende and health- worker strikes in Bas-Uélé and Tshopo further increase the risk of undetected  transmission. 

    The absence of new cases in Kenya since 19  October, the discharge of six  of the seven surviving patients and the imminent end of contact monitoring in  Kenya (11 November) and Nigeria (13 November) indicate that the exported  chains have been contained, although surveillance must be sustained until the  end-of-outbreak criteria are met. Priorities should focus on reinforcing response  capacity in Nord-Kivu, particularly in Beni, Mutwanga, Oicha and Mabalako, restoring contact follow-up and safe burial.

Source: World Health Organization, Regional Office for Africa, https://www.afro.who.int/countries/kenya/publication/bundibugyo-virus-disease-outbreak-democratic-republic-congo-kenya-nigeria-weekly-external-situation

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#Germany - High pathogenicity avian #influenza #H5N1 viruses (Inf. with) ( #poultry ) - Immediate notification

 

{Extract}

(...)

A poultry farm (geese (20), ducks (40), chicken (30)) in the Brandenburg Region.

(...)

Source: World Animal Health Organization, https://wahis.woah.org/#/in-review/7972

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#Finland - #Influenza A #H5N1 viruses of high pathogenicity (Inf. with) (non-poultry including wild birds) (2017-) - Immediate notification

 

{Click on Image to Enlarge}

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By Martin Mecnarowski (http://www.photomecan.eu/) - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=12814916

{Extract}

(...)

A Wild Eurasian Eagle-Owl in the Länsi- ja Sisä-Suomen aluehallintovirasto Region.

(...)

Source: World Animal Health Organization, https://wahis.woah.org/#/in-review/7970

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Avian #Influenza #Report: November 1 - 7 '26 (Wk 45) (HK CHP, November 10 '26): 2 New #Human Infections with #H9N2 virus in #China

 

{Excerpt}

(...)

Avian influenza A(H9N2):

    ° Guangxi Zhuang Autonomous Region:

        § A nine-year-old girl with onset on October 13, 2026.

    ° Liaoning Province:

        § A seven-year-old boy with onset on September 20, 2026.

(...)

Source: Centre for Health Protection, Hong Kong PRC SAR, https://www.chp.gov.hk/files/pdf/2026_avian_influenza_report_vol22_wk45.pdf

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Rare recovery of #reassortants between contemporary clade 2.3.4.4b #H5N1 viruses and #human #influenza A viruses in vitro

 

Abstract

Influenza A virus (IAV) pandemics can arise when animal-derived and human-adapted IAVs exchange genome segments; however, whether contemporary clade 2.3.4.4b H5N1 viruses can generate viable reassortants with human IAVs is unclear. Here, we tested the reassortment potential of two clade 2.3.4.4b H5N1 viruses with human-adapted H1N1 and H3N2 IAVs using a biosafe reassortment system. Across multiple coinfection conditions, we genotyped 2,698 plaque-purified viral clones and recovered 20 reassortants (0.74%). Polymerase assays identified human IAV subunits, particularly H1N1 PA or H3N2 PB2, that increased H5N1 polymerase activity. Thus, contemporary clade 2.3.4.4b H5N1 viruses can reassort with human IAVs, but factors beyond polymerase compatibility may limit their recovery.

Source: Proceedings of the National Academy of Sciences of the United States of America, https://doi.org/10.1073/pnas.2631654123

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#Taiwan, Seasonal #Influenza and #COVID19 #Epidemics, Weekly Situation Update (CDC, Nov. 10 '26): #H1N1pdm09 flu virus still predominated

 

{Extract}

(...)

    The CDC explained that in week 44 (November 1-7), there were 91,879 outpatient and emergency room visits for influenza-like illnesses, a 6.4% decrease from the previous week. 

    However, last week (November 3-9), there were still 103 new cases of severe influenza complications and 38 deaths. 

    This season (October 1, 2026 - September 30, 2027) has seen a cumulative total of 645 severe cases and 124 deaths. 

    The majority of severe cases are among those aged 65 and above (69.6%) and those with a history of chronic illness (85.1%). 

    97.1% of those affected have not received the seasonal influenza vaccine. 

    Laboratory monitoring data shows that H1N1 influenza viruses are currently predominantly circulating in the community, accounting for 94.7%. 

    

    According to the Taiwan Centers for Disease Control (CDC), although the COVID-19 epidemic in Taiwan ended its peak in mid-October and continues to decline, last week (November 3-9) saw 2 new severe cases and 1 death. 

    50% of severe cases have not received the seasonal COVID-19 vaccine. 

    This season (October 1, 2026 - September 30, 2027) saw a cumulative total of 77 severe cases, including 14 deaths. 

    The majority of severe cases were among those aged 65 and above (61.0%) and those with a history of chronic illnesses (84.4%). 98.7% of these cases were not vaccinated against COVID-19 this season.

(...)

Source: Centers for Disease Control and Prevention, Taiwan, https://www.cdc.gov.tw/Bulletin/Detail/HHbAdjZ5sQg8nHVyP5QXSQ?typeid=9

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#Australia, #H5 avian #influenza events in #wildlife (Dept. Agriculture, Nov. 10 '26)

 

{Extract}

(...)

Event data

    As of 4pm AEST, 9 November 2026, Australia has 738 confirmed events of H5 bird flu in wildlife.

        § 10 in Western Australia (WA)

        § 342 in South Australia (SA)

        § 81 in New South Wales (NSW)

        § 2 in Queensland (QLD)

        § 249 in Victoria (VIC)

        § 53 in Tasmania (TAS)^

        § 1 in Other Territories#

    {^} Includes events on Macquarie Island

    {#} Jervis Bay Territory (Commonwealth jurisdiction)

{Click on Image to Enlarge}

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(...)

Source: Australian Department of Agriculture, https://www.agriculture.gov.au/campaigns/birdflu/latest-data#h1_bird_flu

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#UK - High pathogenicity avian #influenza #H5N1 viruses (Inf. with) ( #poultry ) - Immediate notification

 

{Extract}

(...)

{England}

    Poultry premises 67,000 duck meat farm with birds of 35 weeks of age. 

    Samples taken were positive for HPAI H5N1. 

    Birds presented clinical signs prior to testing.

(...)

Source: World Animal Health Organization, https://wahis.woah.org/#/in-review/7964

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Broad #vaccine #protection against globally diverse #influenza #H5Nx viruses

 

Summary

Influenza A/H5Nx viruses continue to diversify and undergo gene reassortment as they infect avian and mammalian hosts worldwide. The severity of human infections varies substantially between different H5 clades and neuraminidase (NA) reassortants, creating unpredictable pandemic risk. Existing H5 vaccines, typically based on a single hemagglutinin (HA) strain, cannot keep pace with this natural variation. To address this problem, we computationally engineer HA, NA, and M2 antigens representing the global antigenic space of circulating H5Nx viruses, prioritizing N1 and N6 subtypes associated with the highest threat in humans. The resulting digitally immune-optimized mRNA vaccine, DVX-panH5Nx, elicits broad HA neutralization and NA inhibition across divergent clades in mice and ferrets. Compared to WHO candidate vaccine viruses (CVVs), DVX-panH5Nx confers superior protection against antigenically distinct H5N1 challenges spanning two decades of viral evolution, demonstrating that computationally designed multivalent antigen vaccines can overcome natural influenza diversification and provide a scalable strategy for pre-pandemic preparedness.

Source: Cell Reports Medicine Journal, https://doi.org/10.1016/j.xcrm.2026.103131

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Immunogenicity and #safety of two priming doses of an MF59-adjuvanted cell-based #H5N8 #influenza #vaccine in healthy persons aged ≥18 years

Abstract

Background

Increased transmission of avian influenza from animals to humans has elevated the risk of an H5 pandemic.

Methods

This phase 2, randomized, observer-blind, multi-center trial assessed the immunogenicity and safety of homologous priming with an MF59-adjuvanted, cell-based H5N8 A/Astrakhan/3212/2020 clade 2.3.4.4b vaccine (aH5N8c). We enrolled adults age ≥18 years, equally stratified into 18–64 (including a poultry-worker subset) and ≥65 year cohorts. Primary and secondary outcomes were homologous antibody responses against H5N8 measured in all participants by hemagglutination inhibition (HI) and in a subset by microneutralization (MN) assays on Days 1, 22, and 43. Solicited adverse events (AEs) were monitored for 7 days post-vaccination, with unsolicited AEs tracked throughout Day 43.

Results

239 participants were vaccinated (18–64 years, n = 121; ≥65 years, n = 118). At Day 43 (21 days post second aH5N8c dose), geometric mean fold increases (GMFI) were 13.7 for the 18–64 cohort and 10.2 for the ≥65 cohort. HI seroconversion rates were 75.8% (95% CI 66.1–83.8%) for the 18–64 cohort and 71.0% (61.1–79.6%) for the ≥65 cohort. HI titers ≥1:40 were achieved in 75.8% (66.1–83.8%) and 73.0% (63.2–81.4%) of participants, respectively. MN seroconversion rates were 80.6% (68.6–89.6%) and 70.0% (56.8–81.2%), while MN titers ≥1:40 were 83.9% (72.3–92.0%) and 86.7% (75.4–94.1%), respectively. No notable differences in immune responses by poultry worker status were observed. Most solicited AEs were mild or moderate, resolving within 3 days. Unsolicited AEs were reported by 16.7% participants by Day 43.

Conclusion

These data support the use of the MF59-adjuvanted, cell-based monovalent H5N8 vaccine as a public health intervention against H5 influenza.

Source: Vaccine Journal, https://doi.org/10.1016/j.vaccine.2026.129279

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Prince Baltasar Carlos, Diego Velazquez (1632)

 

{Click on Image to Enlarge}

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Public Domain.

Source: WikiArt, https://www.wikiart.org/en/diego-velazquez/price-baltasar-carlos-1632

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#Antigenic #landscape of a highly mutated #SARS-CoV-2 #spike in ongoing viral #evolution

 

Abstract

The ongoing emergence of SARS-CoV-2 variants in an increasingly immune-experienced population is largely enabled by the plasticity of the Spike protein, which lies at the frontline of host immune pressure. Here, we investigated how extensive remodeling of the N-terminal domain (NTD) in Spike influences its antigenic properties. Using BA.2.87.1, a variant heavily mutated in this domain, we found that even large deletions do not substantially disrupt overall Spike structure or pseudovirus infectivity. However, our structural and binding analyses revealed that the NTD exhibits increased flexibility and that interaction with a heme–metabolite, known to facilitate the exposure of an immunodominant epitope, is lost. These conformational effects, coupled with 33 NTD mutations, compromised the ability of human convalescent antibodies to engage this domain, contributing to their reduced neutralizing capacity. Consequently, BA.2.87.1-like variants may escape recognition by the preexisting NTD-targeting antibodies, potentially reducing protection. Together, our results highlight the intrinsic adaptability of the Spike beyond the receptor-binding domain, with implications for immune escape during viral evolution.

Source: Proceedings of the National Academy of Sciences of the United States of America, https://doi.org/10.1073/pnas.2608185123

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