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1. The influenza universe in an mRNA vaccine

   https://doi.org/10.1126/science.adf0900  

   Kelvin, Alyson A.; Falzarano, Darryl (November 2022, Science)

   The greatest challenge to preventing the next influenza pandemic is the extensive diversity within the influenza virus family ( 1 ). At present, 20 lineages of influenza A and B viruses have been identified, each containing numerous strains ( 2 , 3 ). Current influenza vaccines, composed of four influenza viral antigens, provide little protection beyond the viral strains targeted by the vaccines. Universal influenza vaccines that can protect against all 20 lineages could help to prevent the next pandemic ( 4 ). Designing and manufacturing a vaccine that can provide such broad protection has been challenging, but the demonstration of the feasibility of mRNA–lipid nanoparticle COVID-19 vaccines offers a possible strategy ( 5 ). On page 899 of this issue, Arevalo et al. ( 6 ) report an influenza vaccine, using mRNA–lipid nanoparticle technology incorporating representatives of all 20 influenza virus lineages, that protected mice and ferrets from diverse influenza viruses. This provides a pathway to a universal influenza vaccine. 

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2. Use Internet search data to accurately track state level influenza epidemics

   https://doi.org/10.1038/s41598-021-83084-5  

   Yang, Shihao; Ning, Shaoyang; Kou, S. C. (December 2021, Scientific Reports)

   null (Ed.)

   Abstract For epidemics control and prevention, timely insights of potential hot spots are invaluable. Alternative to traditional epidemic surveillance, which often lags behind real time by weeks, big data from the Internet provide important information of the current epidemic trends. Here we present a methodology, ARGOX (Augmented Regression with GOogle data CROSS space), for accurate real-time tracking of state-level influenza epidemics in the United States. ARGOX combines Internet search data at the national, regional and state levels with traditional influenza surveillance data from the Centers for Disease Control and Prevention, and accounts for both the spatial correlation structure of state-level influenza activities and the evolution of people’s Internet search pattern. ARGOX achieves on average 28% error reduction over the best alternative for real-time state-level influenza estimation for 2014 to 2020. ARGOX is robust and reliable and can be potentially applied to track county- and city-level influenza activity and other infectious diseases. 

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3. Rapid and label-free influenza A virus subtyping using surface-enhanced Raman spectroscopy with incident-wavelength analysis

   https://doi.org/10.1364/BOE.533457  

   Ricker, RyeAnne; Perea_Lopez, Nestor; Terrones, Mauricio; Loew, Murray; Ghedin, Elodie (August 2024, Biomedical Optics Express)

   Early virus identification is a key component of both patient treatment and epidemiological monitoring. In the case of influenza A virus infections, where the detection of subtypes associated with bird flu in humans could lead to a pandemic, rapid subtype-level identification is important. Surface-enhanced Raman spectroscopy coupled with machine learning can be used to rapidly detect and identify viruses in a label-free manner. As there is a range of available excitation wavelengths for performing Raman spectroscopy, we must choose the best one to permit discrimination between highly similar subtypes of a virus. We show that the spectra produced by influenza A subtypes H1N1 and H3N2 exhibit a higher degree of dissimilarity when using 785 nm excitation wavelength in comparison with 532 nm excitation wavelength. Furthermore, the cross-validated area under the curve (AUC) for identification was higher for the 785 nm excitation, reaching 0.95 as compared to 0.86 for 532 nm. Ultimately, this study suggests that exciting with a 785 nm wavelength is better able to differentiate two closely related influenza viruses and likely can extend to other closely related pathogens. 

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4. Infection dynamics of subtype H9N2 low pathogenic avian influenza a virus in turkeys

   https://doi.org/10.1016/j.virol.2024.110124  

   Ducatez, Mariette F; Wang, Chengcheng; Yang, Jialiang; Zhao, Yulong; Foret-Lucas, Charlotte; Croville, Guillaume; Loupias, Josianne; Teillaud, Angélique; Peralta, Brigitte; Ghram, Abdeljelil; et al (August 2024, Virology)

   Tomar, Jasmine (Ed.)

   While mammals can be infected by influenza A virus either sporadically or with well adapted lineages, aquatic birds are the natural reservoir of the pathogen. So far most of the knowledge on influenza virus dynamics was however gained on mammalian models. In this study, we infected turkeys using a low pathogenic avian influenza virus and determined the infection dynamics with a target-cell limited model. Results showed that turkeys had a different set of infection characteristics, compared with humans and ponies. The viral clearance rates were similar between turkeys and ponies but higher than that in humans. The cell death rates and cell to cell transmission rates were similar between turkeys and humans but higher than those in ponies. Overall, this study indicated the variations of within-host dynamics of influenza infection in avian, humans, and other mammalian systems. 

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5. Co‐Delivery of Multiple Toll‐Like Receptor Agonists and Avian Influenza Hemagglutinin on Protein Nanoparticles Enhances Vaccine Immunogenicity and Efficacy

   https://doi.org/10.1002/adhm.202404335  

   Ramirez, Aaron; Hernandez‐Davies, Jenny_E; Jain, Aarti; Wang, Lu; Strahsburger, Erwin; Davies, D_Huw; Wang, Szu‐Wen (February 2025, Advanced Healthcare Materials)

   Abstract Most seasonal and pandemic influenza vaccines are derived from inactivated or attenuated virus propagated in chicken eggs, while more advanced delivery technologies, such as the use of recombinant proteins and adjuvants, are under‐utilized. In this study, the E2 protein nanoparticle (NP) platform is engineered to synthesize vaccines that simultaneously co‐deliver influenza hemagglutinin (H5) antigen, TLR5 agonist flagellin (FliCc), and TLR9 agonist CpG 1826 (CpG) all on one particle (termed H5‐FliCc‐CpG‐E2), with uniform molecular orientation significant for immunomodulation. Antigen‐bound NP formulations elicit higher IgG antibody responses and broader homosubtypic cross‐reactivity against different H5 variants than unconjugated antigen alone. IgG1/IgG2c skewing is modulated by adjuvant type and NP attachment. Conjugation of flagellin to the NP causes significant IgG1 (Th2) skewing while attachment of CpG yields significant IgG2c (Th1) skewing, and simultaneous conjugation of both flagellin and CpG results in a balanced IgG1/IgG2c (Th2/Th1) response. Animals immunized with E2‐based NP vaccines and subsequently challenged with H5N1 influenza show 100% survival, and only animals that receive adjuvanted NP formulations are also protected against morbidity. This investigation highlights that NP‐based delivery of antigen and multiple adjuvants can be designed to effectively modulate the strength, breadth toward variants, and bias of an immune response against influenza viruses. 

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