Emergence of a Novel #Reassortant Clade 2.3.2.1c Avian #Influenza A #H5N1 Virus Associated with #Human Cases in #Cambodia

Abstract

After nearly a decade without reported human A/H5N1 infections, Cambodia faced a sudden resurgence with 16 cases between February 2023 and August 2024, all caused by A/H5 clade 2.3.2.1c viruses. Fourteen cases involved a novel reassortant A/H5N1 virus with gene segments from both clade 2.3.2.1c and clade 2.3.4.4b viruses. The emergence of this novel genotype underscores the persistent and ongoing threat of avian influenza in Southeast Asia. This study details the timeline and genomic epidemiology of these infections and related poultry outbreaks in Cambodia.

Source: MedRxIV, https://www.medrxiv.org/content/10.1101/2024.11.04.24313747v2

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

 One Cygnus species wild bird in Sachsen Region.

Source: WOAH, https://wahis.woah.org/#/in-review/6245

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Viral #kinetics of #H5N1 #infections in dairy #cattle

Abstract

Since early-2024 unprecedented outbreaks of highly pathogenic avian influenza H5N1 clade 2.3.4.4b have been ongoing in dairy cattle in the United States with significant consequences for the dairy industry and public health. Estimation of key epidemiological parameters is required to support outbreak response, including predicting the likely effectiveness of interventions and testing strategies. Here we pool limited publicly available data from three studies of naturally and experimentally infected dairy cattle. We quantify Ct value trajectories of infected dairy cattle and the relationship between Ct value and the log-titre of infectious virus, a proxy for infectiousness. We estimate that following infection peak Ct values are rapidly reached within 1--2 days with a population mean Ct value of 16.9 (13.2, 20.5). We identify a critical threshold Ct value of 21.5 (20.1, 23.6), with values of Ct value above this threshold representing little-to-no infectious viral load. Finally, we estimate the distribution of the duration of infectiousness for dairy cattle (i.e. the duration their Ct value remains above the critical threshold) with a population median of 6.2 (2.8, 13.1) days.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.02.01.636082v1

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#USA, APHIS Confirms {Avian #Influenza #H5N1} #D11 #Genotype in Dairy #Cattle in #Nevada

On January 31, 2025, the USDA Animal and Plant Health Inspection Service (APHIS) National Veterinary Services Laboratories (NVSL) confirmed by whole genome sequence the first detection of highly pathogenic avian influenza (HPAI) H5N1 clade 2.3.4.4b, genotype D1.1 in dairy cattle. 

This confirmation was a result of State tracing and investigation, following an initial detection on silo testing under the USDA’s National Milk Testing Strategy (NMTS) in Nevada. 

USDA APHIS continues to work with the Nevada Department of Agriculture by conducting additional on-farm investigation, testing, and gathering additional epidemiological information to better understand this detection and limit further disease spread. 

This is the first detection of this virus genotype in dairy cattle (all previous detections in dairy cattle have been HPAI H5N1 clade 2.3.4.4b, genotype B3.13). 

Genotype D1.1 represents the predominant genotype in the North American flyways this past fall and winter and has been identified in wild birds, mammals, and spillovers into domestic poultry. 

The detection does not change USDA’s HPAI eradication strategy and is a testament to the strength of our National Milk Testing Strategy (NTMS). In the interest of sharing information of import to the scientific community, APHIS will publish a technical brief on the findings on our website and post the sequence data on GenBank in the coming week. 

Source: Department of Agriculture, https://www.aphis.usda.gov/news/program-update/aphis-confirms-d11-genotype-dairy-cattle-nevada-0

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Differential #protection against #SARS-CoV-2 #reinfection pre- and post- #Omicron

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly evolved over short timescales, leading to the emergence of more transmissible variants such as Alpha and Delta. The arrival of the Omicron variant marked a major shift, introducing numerous extra mutations in the spike gene compared with earlier variants. These evolutionary changes have raised concerns regarding their potential impact on immune evasion, disease severity and the effectiveness of vaccines and treatments. In this epidemiological study, we identified two distinct patterns in the protective effect of natural infection against reinfection in the Omicron versus pre-Omicron eras. Before Omicron, natural infection provided strong and durable protection against reinfection, with minimal waning over time. However, during the Omicron era, protection was robust only for those recently infected, declining rapidly over time and diminishing within a year. These results demonstrate that SARS-CoV-2 immune protection is shaped by a dynamic interaction between host immunity and viral evolution, leading to contrasting reinfection patterns before and after Omicron’s first wave. This shift in patterns suggests a change in evolutionary pressures, with intrinsic transmissibility driving adaptation pre-Omicron and immune escape becoming dominant post-Omicron, underscoring the need for periodic vaccine updates to sustain immunity.

Source: Nature, https://www.nature.com/articles/s41586-024-08511-9

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

 A wild Barnacle Goose in Rogaland Region.

Source: WOAH, https://wahis.woah.org/#/in-review/6244

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#Italy - #Influenza A #H5N1 viruses of high pathogenicity (Inf. with) (a domestic #cat) (2017-) - Immediate notification

The Database of Global Administrative Boundaries (GADM) used by WAHIS, provides Crespellano as the municipality corresponding to the given coordinates. As a matter of fact the location of the infected premises is the municipality of Valsamoggia Domestic cat found dead on 13 January 2025 at a family poultry farm located in the municipality of Valsamoggia (BO). As expected, the virus has the highest genetic similarity to the H5N1 virus sequenced from poultry from the same farm that tested positive on December 31st. These results confirm that the cat likely became infected following direct exposure to infected poultry at the same site where it was found dead.

Source: WOAH, https://wahis.woah.org/#/in-review/6243

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#KP2 - based monovalent #mRNA #vaccines robustly boost #antibody responses to #SARS-CoV-2

{Excerpt}

In response to the ongoing evolution of SARS-CoV-2, vaccine manufacturers have released updated COVID-19 vaccines annually since 2022. For much of 2024, the global spread was dominated by the JN.1 lineage of viruses,1 which are antigenically quite distant from the XBB.1.5 variant that was used in the previous vaccine booster.2 In August 2024, the US Food and Drug Administration authorised two updated mRNA vaccines (Pfizer–BioNTech and Moderna) based on the spike sequence of KP.2, a subvariant in the JN.1 lineage.3 In the UK and the EU, a KP.2-based mRNA vaccine (BioNTech) was also authorised later in the year.4,5 We have now provided the first indication of the acute boosting effect of updated KP.2 monovalent mRNA vaccines (KP.2 MV) on serum SARS-CoV-2 neutralising antibodies in humans. Since the authorisation of the updated vaccine boosters, SARS-CoV-2 has evolved beyond KP.2, with the subvariant KP.3.1.1 becoming dominant globally and the subvariant XEC now gaining traction rapidly.1 KP.2 contains Arg346Thr, Phe456Leu, and Val1104Leu mutations in spike, in addition to those present in the parental JN.1 (figure A). Both KP.3.1.1 and XEC share Phe456Leu and Val1104Leu mutations found in KP.2, along with Gln493Glu, which is absent in KP.2. In addition, KP.3.1.1 harbors the Ser31del mutation, whereas XEC carries Thr22Asn and Phe59Ser mutations; neither KP.3.1.1 nor XEC possess the Arg346Thr mutation (figure A). The effectiveness of the updated KP.2 MV boosters on neutralising antibodies in human serum against recently dominant subvariants has yet to be reported.

(...)

Source: Lancet Infectious Diseases, https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(25)00058-1/fulltext?rss=yes

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Modeling suggests #SARS-CoV-2 #rebound after #nirmatrelvir-ritonavir #treatment is driven by target cell preservation coupled with incomplete viral clearance

ABSTRACT

In a subset of SARS-CoV-2-infected individuals treated with the antiviral nirmatrelvir-ritonavir, the virus rebounds following treatment. The mechanisms driving this rebound are not well understood. We used a mathematical model to describe the longitudinal viral load dynamics of 51 individuals treated with nirmatrelvir-ritonavir, 20 of whom rebounded. Target cell preservation, either by a robust innate immune response or initiation of N-R near the time of symptom onset, coupled with incomplete viral clearance, appears to be the main factor leading to viral rebound. Moreover, the occurrence of viral rebound is likely influenced by the time of treatment initiation relative to the progression of the infection, with earlier treatments leading to a higher chance of rebound. A comparison with an untreated cohort suggests that early treatments with nirmatrelvir-ritonavir may be associated with a delay in the onset of an adaptive immune response. Nevertheless, our model demonstrates that extending the course of nirmatrelvir-ritonavir treatment to a 10-day regimen may greatly diminish the chance of rebound in people with mild-to-moderate COVID-19 and who are at high risk of progression to severe disease. Altogether, our results suggest that in some individuals, a standard 5-day course of nirmatrelvir-ritonavir starting around the time of symptom onset may not completely eliminate the virus. Thus, after treatment ends, the virus can rebound if an effective adaptive immune response has not fully developed. These findings on the role of target cell preservation and incomplete viral clearance also offer a possible explanation for viral rebounds following other antiviral treatments for SARS-CoV-2.

Source: Journal of Virology, https://journals.asm.org/doi/full/10.1128/jvi.01623-24?af=R

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Highly pathogenic avian #influenza virus (#H5N5) detected in an Atlantic #walrus (Odobenus rosmarus rosmarus) in the #Svalbard Archipelago, #Norway, 2023

ABSTRACT

We present the first documented case of highly pathogenic avian influenza virus (HPAIV) subtype H5N5 in an Atlantic walrus (Odobenus rosmarus rosmarus). The animal was found dead in Svalbard, Norway, in 2023. Sequence analysis revealed the highest genetic similarity with virus isolates from different avian hosts.

Source: Emerging Microbes and Infections, https://www.tandfonline.com/doi/full/10.1080/22221751.2025.2456146

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

 Three wild Hooded Cranes in Izumi Region, Kagoshima city.

Source: WOAH, https://wahis.woah.org/#/in-review/6239

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Groundbreaking #Ebola #vaccination #trial launches today in #Uganda

{Excerpt}

In a global first, Uganda’s Ministry of Health, the World Health Organization (WHO) and other partners today launched a first ever vaccine trial for Ebola from the Sudan species of the virus, and at an unprecedented speed for a randomized vaccine trial in an emergency.

The principal investigators from Makerere University and the Uganda Virus Research Institute (UVRI), with support from WHO and other partners, have worked tirelessly to get the trial ready in 4 days since the outbreak was confirmed on 30 January. It is the first trial to assess the clinical efficacy of a vaccine against Ebola disease due to Sudan virus. The speed was achieved through advanced research preparedness, while ensuring full compliance with national and international regulatory and ethical requirements.

The candidate vaccine was donated by IAVI, with financial support from WHO, the Coalition for Epidemic Preparedness Innovations (CEPI), Canada’s International Development Research Centre (IDRC), and the European Commission's Health Emergency Preparedness and Response Authority (HERA) and support from the Africa Centres for Disease Control and Prevention (Africa CDC).

“This is a critical achievement towards better pandemic preparedness, and saving lives when outbreaks occur,” said Dr Tedros Adhanom Ghebreyesus, WHO’s Director-General.  

“This is possible because of the dedication of Uganda’s health workers, the involvement of communities, the Ministry of Health of Uganda, Makerere University and UVRI, and research efforts led by WHO involving hundreds of scientists through our research and development Filoviruses network. We thank our partners for their dedication and cooperation, from IAVI for donating the vaccine, to CEPI, EU HERA and Canada’s IDRC for funding, and Africa CDC for further support. This massive achievement would simply not be possible without them.”

In 2022, during the previous outbreak of Ebola disease (also from the Sudan species of the virus) in Uganda, a randomized protocol for candidate vaccines was developed. Principal investigators were designated under the leadership of the Minister of Health, and teams were trained to allow such a trial to take place during an active outbreak.

The randomized vaccine trial to assess the recombinant vesicular stomatitis virus (rVSV) candidate vaccine was launched at a ceremony in Kampala today by the Minister of Health of Uganda. WHO is co-sponsoring the trial. WHO was represented by Dr Mike Ryan, Executive Director of WHO’s Health Emergencies Programme and Deputy Director-General, and the WHO representative to Uganda Dr Kasonde Mwinga, along with other colleagues.

Three vaccination rings were defined today. The first ring involves about 40 contacts and contacts of contacts of the first reported and confirmed case, a health worker who has died.

Although several promising candidate medical countermeasures are progressing through clinical development, as of now, there is no licensed vaccine available to effectively combat a potential future outbreak of Ebola disease from the Sudan species of the virus. Licensed vaccines exist only for the disease caused by Ebola virus, formerly known as Zaïre ebolavirus. Likewise for treatments, approved treatments are only available for Ebola virus.

The vaccine for the trial was recommended by the independent WHO candidate vaccine prioritization working group. If the candidate vaccine is effective, it can contribute to controlling this outbreak and generate data for vaccine licensure.

In 2022, the research teams were trained in good clinical practice (GCP) and standard operating procedures for such trials. They completed refresher training in recent days. WHO colleagues experienced in trials and in ring vaccination arrived in Uganda over the weekend to support the trial implementation and GCP compliance.

The vaccine doses were pre-positioned in the country. WHO worked with the principal investigators and national authorities and the vaccine developer to review cold chain documentation and ensure the doses were stored correctly over the previous years. As part of the signed agreement with the Ministry of Health, WHO has a signed agreement with IAVI for additional doses of the candidate vaccine to be made available shortly.

(...)

Source: World Health Organization, https://www.who.int/news/item/03-02-2025-groundbreaking-ebola-vaccination-trial-launches-today-in-uganda

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Development of avian #influenza A(#H5) virus #datasets for #Nextclade enables rapid and accurate clade assignment

Abstract

The ongoing panzootic of highly pathogenic avian influenza (HPAI) A(H5) viruses is the largest in history, with unprecedented transmission to multiple mammalian species. Avian influenza A viruses of the H5 subtype circulate globally among birds and are classified into distinct clades based on their hemagglutinin (HA) genetic sequences. Thus, the ability to accurately and rapidly assign clades to newly sequenced isolates is key to surveillance and outbreak response. Co-circulation of endemic, low pathogenic avian influenza (LPAI) A(H5) lineages in North American and European wild birds necessitates the ability to rapidly and accurately distinguish between infections arising from these lineages and epizootic HPAI A(H5) viruses. However, currently available clade assignment tools are limited and often require command line expertise, hindering their utility for public health surveillance labs. To address this gap, we have developed datasets to enable A(H5) clade assignments with Nextclade, a drag-and-drop tool originally developed for SARS-CoV-2 genetic clade classification. Using annotated reference datasets for all historical A(H5) clades, clade 2.3.2.1 descendants, and clade 2.3.4.4 descendants provided by the Food and Agriculture Organization/World Health Organization/World Organisation for Animal Health (FAO/WHO/WOAH) H5 Working Group, we identified clade-defining mutations for every established clade to enable tree-based clade assignment. We then created three Nextclade datasets which can be used to assign clades to A(H5) HA sequences and call mutations relative to reference strains through a drag-and-drop interface. Nextclade assignments were benchmarked with 19,834 unique sequences not in the reference set using a pre-released version of LABEL, a well-validated and widely used command line software. Prospective assignment of new sequences with Nextclade and LABEL produced very well-matched assignments (match rates of 97.8% and 99.1% for the 2.3.2.1 and 2.3.4.4 datasets, respectively). The all-clades dataset also performed well (94.8% match rate) and correctly distinguished between all HPAI and LPAI strains. This tool additionally allows for the identification of polybasic cleavage site sequences and potential N-linked glycosylation sites. These datasets therefore provide an alternative, rapid method to accurately assign clades to new A(H5) HA sequences, with the benefit of an easy-to-use browser interface.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.01.07.631789v2

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

 A wild cygnus species birds in Sachsen-Anhalt Region.

Source: WOAH, https://wahis.woah.org/#/in-review/6234

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

Forty Mute Swans in Lviv Region.

Source: WOAH, https://wahis.woah.org/#/in-review/6232

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The Emergence of #Coxsackievirus A16 Subgenotype B1c: A Key Driver of the #HFMD #Epidemic in #Guangdong, #China

Abstract

Background: 

In 2024, mainland China witnessed a significant upsurge in Hand, Foot, and Mouth Disease (HFMD) cases. Coxsackievirus A16 (CVA16) is one of the primary causative agents of HFMD. Long-term monitoring of theCVA16 infection rate and genotype changes is crucial for the prevention and control of HFMD. 

Methods: 

A total of 40,673 clinical specimens were collected from suspected HFMD cases in Guangdong province from 2018 to 2024, including rectal swabs (n = 27,954), throat swabs (n = 6791), stool (n = 5923), cerebrospinal fluid (n = 3), and herpes fluid (n = 2). A total of 24,410 samples were detected as EV-positive and further typed by RT-PCR. A total of 872 CVA16-positive samples were isolated and further sequenced to obtain the full-length VP1 sequence. Phylogenetic analysis was performed based on viral protein 1 gene (VP1). 

Results: 

In the first 25 weeks of 2024, reported cases of HFMD were 1.36 times higher than the mean rates of 2023. In 2024, CVA16 predominated at 75.42%, contrasting with the past etiological pattern in which the CVA6 was predominant with the detection rate ranging from 32.85 to 77.61% from 2019 to 2023. Phylogenetic analysis based on the VP1 gene revealed that the B1a and B1b subtypes co-circulated in Guangdong from 2018 to 2022. The B1c outbreak clade, detected in Guangdong in 2023, constituted 68.24% of the 148 strains of CVA16 collected in 2024, suggesting a subtype shift in the CVA16 virus. There were three specific amino acid variations (P3S, I235V, and T240A) in the VP1 sequence of B1c. 

Conclusions: 

The new emergence of the CVA16 B1c outbreak clade in Guangdong during 2023–2024 highlights the necessity for the enhanced surveillance of the virus evolution epidemiological dynamic in this region. Furthermore, it is imperative to closely monitor the etiological pattern changes in Hand, Foot, and Mouth Disease (HFMD) in other regions as well. Such vigilance will be instrumental in guiding future vaccination strategies for HFMD.

Source: Viruses, https://www.mdpi.com/1999-4915/17/2/219

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The Madonna of the Pesaro Family, Titian (1519-26)

 Public Domain.

Source: WikiArt, https://www.wikiart.org/en/titian/pesaros-madonna-1526

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Distal #protein-protein #interactions contribute to #nirmatrelvir #resistance

Abstract

SARS-CoV-2 main protease, Mpro, is responsible for processing the viral polyproteins into individual proteins, including the protease itself. Mpro is a key target of anti-COVID-19 therapeutics such as nirmatrelvir (the active component of Paxlovid). Resistance mutants identified clinically and in viral passage assays contain a combination of active site mutations (e.g., E166V, E166A, L167F), which reduce inhibitor binding and enzymatic activity, and non-active site mutations (e.g., P252L, T21I, L50F), which restore the fitness of viral replication. To probe the role of the non-active site mutations in fitness rescue, here we use an Mpro triple mutant (L50F/E166A/L167F) that confers nirmatrelvir drug resistance with a viral fitness level similar to the wild-type. By comparing peptide and full-length Mpro protein as substrates, we demonstrate that the binding of Mpro substrate involves more than residues in the active site. Particularly, L50F and other non-active site mutations can enhance the Mpro dimer-dimer interactions and help place the nsp5-6 substrate at the enzyme catalytic center. The structural and enzymatic activity data of Mpro L50F, L50F/E166A/L167F, and others underscore the importance of considering the whole substrate protein in studying Mpro and substrate interactions, and offers important insights into Mpro function, resistance development, and inhibitor design.

Source: Nature Communications, https://www.nature.com/articles/s41467-025-56651-x

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#Pandemic #preparedness: analyzing national #plans for respiratory #pathogen pandemics in the #Americas region

Abstract

Background

The International Health Regulations (2005) (IHR), requires that States Parties develop their capacities to detect, assess, and respond to public health threats and report to the World Health Assembly through the States Parties Annual Report (SPAR). The National Pandemic Preparedness and Response Plans (PPRP) contribute to countries capacities however there are some discrepancies between both tools. To identify gaps and define priority actions to strengthen pandemic plans, we assessed the concordance between national pandemic preparedness and response plans for respiratory pathogens against the pandemic checklist published in 2023 and the SPAR.

Methods

In this retrospective, semi-quantitative study, conducted in August 2024, we reviewed the most recent respiratory pandemic plans for 35 PAHO member states and assessed their concordance with (1) actionable guidelines in the World Health Organization pandemic checklist and (2) IHR (2005) core capacities using the latest SPAR tool. We developed 25 tracking questions to identify gaps, strengths, and opportunities for improvement in the pandemic plans, using the pandemic checklist built on the capacities and capabilities described in the WHO’s Preparedness and Resilience for Emerging Threats (PRET) Module 1. We used a five-point scale (from 1, when the subcomponent was not mentioned, to 5, when the subcomponent was described at all levels), and we calculated the average pandemic plans score (PP score) for each component. Data from pandemic plans (2005–2024) were compiled, selected, analyzed, and scored. We compared the average SPAR score and the PP score to assess areas of convergence and variance between preparedness and capacities. The analysis was carried out using R and Excel.

Results

We analyzed 35 respiratory pandemic plans: 29 were influenza-specific, five were COVID-19-specific, and one was not pathogen-specific. Most current national plans showed limited alignment with the content recommended in the PRET pandemic checklist. At regional level, the lowest concordance between plans and pandemic checklist was in the following subcomponents Public Health and Social Measures (80% of the plans had a score of 1); Emergency, Logistics and Supply Chain Management (74%); and Research and Development (71%). Conversely, the strongest subcomponents (≥40% of plans with a score of 4 or 5) were: Policy, Legal, and Normative Instruments (45%); Coordination (46%); and Surveillance: early detection and assessment (43%). In most countries, the SPAR scores tended to be higher than PP scores, except for Argentina (the newest plan reviewed) for which the pattern was reversed, and the PP scores exceeded the SPAR scores.

Conclusion

Given the gaps identified between current plans and the global standards espoused by the PRET Module 1 initiative, it is recommended that countries build on the strengths of their national pandemic preparedness and response plans and update them using PRET module 1. This will support countries advance the capacities required by the IHR.

Source: Journal of Infectious Diseases, https://academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiaf047/7994597

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Structurally convergent #antibodies derived from different #vaccine #strategies target the #influenza virus HA anchor epitope with a subset of VH3 and VK3 genes

Abstract

H1N1 influenza viruses are responsible for both seasonal and pandemic influenza. The continual antigenic shift and drift of these viruses highlight the urgent need for a universal influenza vaccine to elicit broadly neutralizing antibodies (bnAbs). Identification and characterization of bnAbs elicited in natural infection and immunization to influenza virus hemagglutinin (HA) can provide insights for development of a universal influenza vaccine. Here, we structurally and biophysically characterize four antibodies that bind to a conserved region on the HA membrane-proximal region known as the anchor epitope. Despite some diversity in their VH and VK genes, the antibodies interact with the HA through germline-encoded residues in HCDR2 and LCDR3. Somatic mutations on HCDR3 also contribute hydrophobic interactions with the conserved HA epitope. This convergent binding mode provides extensive neutralization breadth against H1N1 viruses and suggests possible countermeasures against H1N1 viruses.

Source: Nature Communications, https://www.nature.com/articles/s41467-025-56496-4

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