Wood JM. ; methodology, A.D.P., N.P., M.J.M., H.Z., B.Z., and G.S. ; McLean, H.Q. Curr Opin Mol Ther 2008; 10:75–85. Raymond, D.D. HA is an antigen, which is a feature of a flu virus that triggers the human immune system to … Richards KA, Moritzky S, Shannon I, Fitzgerald T, Yang H, Branche A, Topham DJ, Treanor JJ, Nayak J, Sant AJ. ; Kaur, K.; Andrews, S.F. @article{McCraw2016CharacterizationOI, title={Characterization of Influenza Vaccine Hemagglutinin Complexes by Cryo-Electron Microscopy and Image Analyses Reveals Structural Polymorphisms}, author={Dustin M. McCraw and J. Gallagher and A. Harris}, journal={Clinical and Vaccine Immunology : … This review discusses the four main clinical studies that were used to support licensure of FluBlok under the 'Accelerated Approval' mechanism in the United States. Previous studies on potential influenza vaccines showed that vaccine based only on influenza virus NP proved unusable. Due to the frequent and unpredictable mutations caused by antigenic sites, universal influenza vaccines can offer more reliable and broad-spectrum immunity. ; Metlagel, Z.; Bujny, M.V. ; Stevens, J. Prevention and control of influenza, recommendations of the advisory committee on immunization practices. The impact of influenza epidemics on mortality: Introducing a severity index. The funder had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The emergence of the swine-origin 2009 influenza pandemic illustrates the need for improved vaccine production and delivery strategies. A Site of Vulnerability on the Influenza Virus Hemagglutinin Head Domain Trimer Interface. King JC Jr, Cox MM, Reisinger K, Hedrick J, Graham I, Patriarca P. Vaccine. Lander, G.C. 2009 Jun;37(3):182-9. doi: 10.1016/j.biologicals.2009.02.014. Influenza immunization elicits antibodies specific for an egg-adapted vaccine strain. The trivalent (IIV3) and quadrivalent (IIV4) inactivated influenza vaccines … Therefore, inactivated trivalent influenza vaccines are standardized to contain the hemagglutinin of influenza virus strains (two subtypes A and one type B), representing the influenza viruses likely to be circulating in the United States in the upcoming influenza … ; Parkhouse, K.; Gumina, M.E. ; Sullivan, S.G.; Subbarao, K.; Fauci, A.S. Chasing Seasonal Influenza—The Need for a Universal Influenza Vaccine. ; Post, D.J. The Influenza Genome Sequencing Projectis creating a library of influenza sequences that will help research… Background The A/H1N1/2009 influenza pandemic made evident the need for faster and higher-yield methods for the production of influenza vaccines. Skin-based immunization represents an attractive alternative to traditional hypodermic needle vaccination routes. ; O’Neil, R.E. As previously described, BLI was used to evaluate immune sera for antibodies that cross-competed with the hybridoma isolated murine mAbs, A2.91.3 and A2.4.1, and the stem mAb, CR8020 [, Murine IgG1 heavy and light chains were codon optimized for mammalian expression and synthesized by GenScript (Piscataway, NJ, USA). In a phase 1 clinical trial of older adults, the vaccine demonstrated broadly cross-reactive A(H3N2) HA antibody responses. ; Thompson, L.F.; Air, G.M. ; Oyen, D.; Nycholat, C.M. Traditional flu vaccine targets the globular head of HA to prevent the virus from binding to human cells. -. Crooks, G.E. A universal vaccine against influenza remains a critical target, and efforts have recently focused on the stem of the hemagglutinin glycoprotein. Zheng, Z.; Paul, S.S.; Mo, X.; Yuan, Y.A. COVID-19 is an emerging, rapidly evolving situation. Bangaru, S.; Lang, S.; Schotsaert, M.; Vanderven, H.A. Estimating influenza disease burden from population-based surveillance data in the United States. 2007 Jan;1(1):35-40. doi: 10.1111/j.1750-2659.2006.00007.x. Lee, P.S. Wild-type and egg passage HA sequences were compared to published sequences in the GISAID EpiFlu database. International Laboratory Comparison of Influenza Microneutralization Assays for A(H1N1)pdm09, A(H3N2), and A(H5N1) Influenza Viruses by CONSISE. FluBlok, a next generation influenza vaccine manufactured in insect cells. Interestingly, the monoglycosylated cHA (cHA mg) vaccine with GlcNAc on each glycosite induced more stem-specific antibodies, with higher antibody-dependent cellular cytotoxicity (ADCC), and better neutralizing and stronger cross-protection activities against H1, … ; Arden, N.H.; Schonberger, L.B. Impagliazzo, A.F., et al., 2015. Structural characterization of viral epitopes recognized by broadly cross-reactive antibodies. Development of Universal Influenza Vaccines Targeting Conserved Viral Proteins. Immunogenicity of inactivated influenza vaccines (IIVs) is usually analyzed using hemagglutination inhibition (HAI) assay, which measures antibodies targeted against the globular head domain of hemagglutinin (HA), the immunodominant major surface glycoprotein of the virus [ 2–6 ]. Structural identification of the antibody-binding sites of Hong Kong influenza haemagglutinin and their involvement in antigenic variation. King JC Jr(1), Cox MM, Reisinger K, Hedrick J, … eCollection 2020. Steel J. Get the latest public health information from CDC: https://www.coronavirus.gov, Get the latest research information from NIH: https://www.nih.gov/coronavirus, Find NCBI SARS-CoV-2 literature, sequence, and clinical content: https://www.ncbi.nlm.nih.gov/sars-cov-2/. ; Engelhardt, O.G. Current influenza virus vaccines mostly target the immunodominant head domain of the viral hemagglutinin (HA) and are therefore strain specific 8. Henry, C.; Zheng, N.Y.; Huang, M.; Cabanov, A.; Rojas, K.T. Here, we show that prime-boost vaccination with a TLR7/8 agonist (R848)-conjugated influenza A virus vaccine elicits antibody responses to the highly conserved hemagglutinin stem and … 9,10 High-dose vaccine … The conserved stalk of the viral hemagglutinin has been identified as potential target antigen for this new generation of vaccines. Influenza research includes molecular virology, molecular evolution, pathogenesis, host immune responses, genomics, and epidemiology. ; writing—original draft preparation, A.D.P., N.P., H.Z., and G.S. The Vestigial Esterase Domain of Haemagglutinin of H5N1 Avian Influenza A Virus: Antigenicity and Contribution to Viral Pathogenesis. ; Graham, B.S. Persistent Antibody Clonotypes Dominate the Serum Response to Influenza over Multiple Years and Repeated Vaccinations. Viruses used in the neutralization assay had their HA gene sequenced to confirm it contained the wild-type genotype and did not contain any egg adapted mutations. ; Wu, N.C.; Hensley, S.E. Kochhar S, Kim D, Excler JL, Condit RC, Robertson JS, Drew S, Whelan M, Wood D, Fast PE, Gurwith M, Klug B, Khuri-Bulos N, Smith ER, Chen RT; Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG). ; Yu, W.; McBride, R.; Paulson, J.C.; Yuen, K.Y. ; Glenn, G.; Ellingsworth, L.; Smith, G. Respiratory syncytial virus fusion nanoparticle vaccine immune responses target multiple neutralizing epitopes that contribute to protection against wild-type and palivizumab-resistant mutant virus challenge. ; Treanor, J.J.; Sant, A.J. ; Garcia-Sastre, A.; et al. CVVs are influenza viruses that can be used commercially to produce vaccines to prevent influenza disease. ; McBride, R.; Paulson, J.C.; Hensley, S.E. ; Bowman, C.A. ; Hussein, D.A. ; Pascual-Montano, A. XMIPP: A new generation of an open-source image processing package for electron microscopy. Viruses were obtained from the Centers for Disease Control and Prevention, Atlanta, GA, USA. Highlight: Influenza vaccine needs to be administered … ; Stewart, S.M. ; Kwaks, T.; Zuijdgeest, D.; Khayat, R.; Ekiert, D.C.; Lee, J.H. Please let us know what you think of our products and services. Hemagglutinin is the major antigen (structure) against which the host’s protective antibody response is directed and is responsible for attachment of influenza viruses to the cell surface … ; Osterholm, M.T. ; Moody, M.A. Improved Titers against Influenza Drift Variants with a Nanoparticle Vaccine. The only effective measure to decrease morbidity and mortality caused by the influenza virus in the human population is worldwide vaccination. ; King, J.P.; Sundaram, M.E. High doses of purified influenza A virus hemagglutinin significantly augment serum and nasal secretion antibody responses in healthy young adults. Gilbert, B.E. Appion: An integrated, database-driven pipeline to facilitate EM image processing. ; Parkhouse, K.; Ross, T.M. Vacunas. All authors have read and agreed to the published version of the manuscript. For antibodies bound to HA, Fab fragments were generated using the Pierce, Influenza virus HA wild-type sequences were taken from published sequences in the GISAID EpiFlu database and accession numbers are listed in. influenza; hemagglutinin; nanoparticle; vaccine; antibody, Help us to further improve by taking part in this short 5 minute survey, Downregulation of A20 Expression Increases the Immune Response and Apoptosis and Reduces Virus Production in Cells Infected by the Human Respiratory Syncytial Virus, The Utility of Human Immune System Mice for High-Containment Viral Hemorrhagic Fever Research, http://creativecommons.org/licenses/by/4.0/, A/Singapore/0019/2016—egg-passaged (T160K, L194P). Vaccine 19:1732–1737 . Please cite this paper as: Getie‐Kebtie et al. If there is an antigenic mismatch between these proteins in the influenza vaccines and cocirculating influenza isolates, there is a decrease in the vaccine effectiveness in vaccinated persons. Epub 2020 Jul 9. HA NP samples were imaged over a layer of continuous carbon supported by nitro-cellulose on a 400 mesh copper grid. ; et al. Biologicals. ; Jongeneelen, M.; et al. ; Wu, N.C.; Bedford, T.; Bloom, J.D. Localization of epitopes recognized by monoclonal antibodies that neutralized the H3N2 influenza viruses in man. These interests do not alter the authors’ adherence to policies on sharing data and materials. ; Zhu, X.; Kose, N.; Bombardi, R.; Finn, J.A. Morbidity and Mortality Weekly Report (MMWR) 2002; 51:1–31. ; investigation, A.D.P., N.P., H.Z., and B.Z. Zost, S.J. Turner, H.L. 2011 Oct 13;29(44):7733-9. doi: 10.1016/j.vaccine.2011.07.128. Influenza Virus Vaccination Elicits Poorly Adapted B Cell Responses in Elderly Individuals. Would you like email updates of new search results? ; project administration, N.P., M.J.M., V.S., G.M.G., and G.S. Maier, J.K.; Labute, P. Assessment of fully automated antibody homology modeling protocols in molecular operating environment. ; Kim, K.; Diaz Perez, S.; Wilson, P.C. Together, this study describes Mab-induced destabilization of the influenza HA stem domain, faster kinetics of influenza virus fusion, and ERD in vivo. Clipboard, Search History, and several other advanced features are temporarily unavailable. HHS 2011. It is a trivalent recombinant hemagglutinin (HA) vaccine, produced by Protein Sciences Corporation, that contains HA antigen derived from three influenza virus … Docking simulations were performed with the Receptor defined as the truncated HA trimer and site targeted as the shallow base of the RBS (Y98, W153, and Y195). ; Huffman, C.J. A universal vaccine against influenza remains a critical target, and efforts have recently focused on the stem of the hemagglutinin glycoprotein. ; Irving, R.P. A stable trimeric influenza hemagglutinin stem as a broadly protective immunogen. Hemagglutinin (HA) is the major antigen in influenza vaccines, and glycosylation is known to influence its antigenicity. Influenza vaccines usually encourage the body to … Cross-neutralization of influenza A viruses mediated by a single antibody loop. Immunodominance and Antigenic Variation of Influenza Virus Hemagglutinin: Implications for Design of Universal Vaccine Immunogens. ; Butler, L.; Baumbach, J.; Hollick, G.; Bennett, N.M.; et al. ; Wilson, I.A. Las vacunas de la gripe basadas en las partículas. The development of anti-IAV vaccines and therapeutics is urgently needed for prevention and treatment of IAV infection and for controlling future influenza pandemics. ; Simpson, M.D. Laurie, K.L. ; Yu, W.; Iba, Y.; Okuno, Y.; Kurosawa, Y.; Wilson, I.A. Iba, Y.; Fujii, Y.; Ohshima, N.; Sumida, T.; Kubota-Koketsu, R.; Ikeda, M.; Wakiyama, M.; Shirouzu, M.; Okada, J.; Okuno, Y.; et al. To make a recombinant vaccine, flu scientists first obtain DNA, i.e., genetic instructions, for making a surface protein called hemagglutinin (HA) found on influenza viruses. Ekiert, D.C.; Friesen, R.H.; Bhabha, G.; Kwaks, T.; Jongeneelen, M.; Yu, W.; Ophorst, C.; Cox, F.; Korse, H.J. To address these limitations, we have developed a hemagglutinin (HA)-based protein-detergent nanoparticle influenza vaccine (NIV) with a saponin-based Matrix-M™ adjuvant. ; Tanno, Y.; Pappas, L.; et al. ; Deem, M.W. Krause, J.C.; Tsibane, T.; Tumpey, T.M. FluBlok contains three times more HA than TIV and does not contain egg-protein or preservatives. ; Stagg, S.M. ; writing—review and editing, A.D.P, N.P., M.J.M., G.M.G., and G.S. Simonsen, L.; Reichert, T.A. NIH Antibody competition studies with sera from the phase 1 trial in older adults confirmed that humans also make antibodies to these two head domains and against the highly conserved stem domain. 2020 Jul 31;38(35):5734-5739. doi: 10.1016/j.vaccine.2020.06.044. FluBlok, a recombinant influenza vaccine. These antibodies often have … Due to limitations of current influenza virus vaccines, new vaccines that mediate broad protection and show high efficacy against seasonal and pandemic viruses are urgently needed. These antibodies recognize two conserved regions of the head domain, namely the receptor binding site and the vestigial esterase subdomain, thus demonstrating the potential for an HA subunit vaccine to elicit antibodies targeting structurally and antigenically distinct but conserved sites. Ekiert, D.C.; Kashyap, A.K. FluBlok, a recombinant trivalent hemagglutinin (HA) vaccine produced in insect cell culture using the baculovirus expression system, provides an attractive alternative to the current egg-based trivalent inactivated influenza vaccine (TIV) manufacturing process. Vaccination is the most effective method to control seasonal infections and the most important strategy to prepare for a possible pandemic. Production of a novel influenza vaccine using insect cells: protection against drifted strains. ; Wilson, I.A. 2021 Jan 20:S0169-409X(21)00024-7. doi: 10.1016/j.addr.2021.01.014. FluBlok, a recombinant trivalent hemagglutinin (HA) vaccine produced in insect cell culture using the baculovirus expression system, provides an attractive alternative to the current egg-based trivalent inactivated influenza vaccine (TIV) manufacturing process. Deep mutational scanning of hemagglutinin helps predict evolutionary fates of human H3N2 influenza variants. ; Lee, J.; Ferdman, J.; Bajic, G.; Do, K.T. The tested chimeric haemagglutinin-based, universal influenza virus vaccine regimens elicited cross-reactive serum IgG antibodies that targeted the conserved haemagglutinin stalk domain. ; Dillon, M.A. Simonsen, L.; Clarke, M.J.; Williamson, G.D.; Stroup, D.F. Received: 21 January 2020 / Revised: 17 February 2020 / Accepted: 18 February 2020 / Published: 22 February 2020. ; Voss, N.R. Two broadly neutralizing monoclonal antibodies derived from NIV-immunized mice were characterized by transmission electron microscopy (TEM), antibody competition assays, fluorescence-activated cell sorting (FACS) analysis, and protein–protein docking. ; Haynes, B.F.; Walter, E.B. Xu, X.; Blanton, L.; Elal, A.I.A. 2019 Nov 1;7(4):169. doi: 10.3390/vaccines7040169. Subscribe to receive issue release notifications and newsletters from MDPI journals, You can make submissions to other journals. ; et al. Paules, C.I. Vaccines (Basel). Abstract. Recombinant influenza vaccine.183 Seasonal influenza vaccine recombinant (RIV; RIV4) contains recombinant hemagglutinin (HA) proteins representing influenza virus types A and B likely to circulate in the US during the upcoming season and is used to stimulate active immunity to influenza strains contained in the vaccine.100 183 FluBlok contains three times more HA t … High-dose influenza vaccine contains 4 times the amount of hemagglutinin compared with standard-dose vaccine, and reduced laboratory-confirmed symptomatic influenza in a large randomized clinical trial compared with standard-dose influenza vaccine. 2019 Jul 3. pii: JVI.00570-19. Since hemagglutinin is the major surface protein of the influenza A virus and is essential to the entry process, it is the primary target of neutralizing antibodies. HA2 has much less probability of antigenic variation co… Influenza virus surface glycoprotein hemagglutinin (HA) is an excellent and chief target that elicits neutralizing antibodies during vaccination or natural infection. Introduction. 2009 Nov 5;27(47):6589-94. doi: 10.1016/j.vaccine.2009.08.032. ; Burns, E.; Cummings, C.N. ; Ramos, I.; Fernandez-Sesma, A.; Edwards, K.M. ; Kent, S.J. FluBlok, a trivalent recombinant hemagglutinin (rHA) vaccine, is under development by Protein Sciences Corporation. ; Palese, P.; Ravetch, J.V. Dreyfus, C.; Laursen, N.S. J Clin Microbiol 1994; 32:2468–2473. Smith, G.; Liu, Y.; Flyer, D.; Massare, M.J.; Zhou, B.; Patel, N.; Ellingsworth, L.; Lewis, M.; Cummings, J.F. , 87 ( 2013 ) , pp. Influenza vaccine efficacy and regulatory approval depends on the HAI assay although it only captures a limited subset of serum antibodies. Receptor mimicry by antibody F045-092 facilitates universal binding to the H3 subtype of influenza virus. Authors A.D.P., N.P., M.J.M., H.Z., J.-H.T., B.Z., V.S., G.M.G., and G.S. Clin Diagn Lab Immunol 1996; 3:507–510. ; Fruhwirth, A.; McDaniel, J.R.; Jung, J.; Boutz, D.R. A highly conserved neutralizing epitope on group 2 influenza A viruses. are current employees of Novavax, Inc, a for-profit organization and these authors may own stock or hold stock options. ; Pallesen, J.; Lang, S.; Bangaru, S.; Urata, S.; Li, S.; Cottrell, C.A. Inactivated influenza vaccines target the head domain of the viral hemagglutinin (HA), a highly mutable region that allows the virus to escape neutralization through antigenic drift. ; Viboud, C.; Blackwelder, W.C.; Taylor, R.J.; Miller, M.A. To gain a fuller understanding of the immune response elicited by our HA nanoparticle vaccine with Matrix-M adjuvant, we used the RBS A2.91.3 and VE subdomain A2.4.1 antibodies to characterize the antibody response in a pre-clinical ferret study [, In both pre-clinical and early clinical trial testing of our trivalent HA nanoparticle vaccine, we observed broader neutralization and improved HAI titers compared to a licensed influenza vaccine when testing historical H3N2 strains from the past decade [, In development of a vaccine for a virus with significant seasonal antigenic drift such as influenza A(H3N2) strains, it is critical that vaccine-induced antibody responses cover multiple antigenic sites to improve the capability to neutralize divergent circulating strains [, Recent experience with the rapid evolution of A(H3N2) influenza strains, and the consequent disappointing vaccine efficacy over multiple seasons, highlights the need for vaccine strategies which can provide protection against strains that have evolved beyond those included in the vaccine. USA.gov. You seem to have javascript disabled. Belongia, E.A. Human monoclonal antibodies to pandemic 1957 H2N2 and pandemic 1968 H3N2 influenza viruses. These vaccines elicit antibodies that target the surface viral glycoproteins hemagglutinin and neuraminidase. This data supports the potential of an adjuvanted recombinant HA nanoparticle vaccine to induce broadly protective immunity and improved vaccine efficacy. The winter of 2003–2004 will be remembered as a year in which stories about influenza dominated the news and patients young and old clamored for influenza vaccination. Influenza disease burden in the United States is estimated to cause 140,000–960,000 hospitalizations each year and 12,000–79,000 deaths according to the Centers for Disease Control and Prevention (CDC) reporting over the last eight seasons [, To date, many broadly neutralizing antibodies (bnAbs) have been isolated and characterized targeting either the highly conserved stem domain or the more variable receptor binding site (RBS) on the head of HA [, Efforts toward a universal vaccine emphasize the need to elicit broad and durable immunity to protect against seasonal drift variants while avoiding the introduction of egg-derived mutations, but this goal has not yet been achieved [, The ferret study was performed at IIT Research Institute, Chicago, IL, USA, in accordance with the study protocol approved by the IITRI Institutional Animal Care and Use Committee.  |  The HA … New strategies for the development of H5N1 subtype influenza vaccines: progress and challenges. Wu, N.C.; Zost, S.J. 2011 Mar 9;29(12):2272-8. doi: 10.1016/j.vaccine.2011.01.039. Platforms based on virus culture in mammalian or insect cells are currently under investigation. BioDrugs 25:285–298 . Many universal influenza vaccine constructs focus on conserved regions of the HA protein [2, 6, 9]. Samples were imaged over a layer of continuous carbon supported by nitro-cellulose a. Or preparation of the page functionalities wo n't work as expected without enabled. And G.S a novel influenza vaccine administered intramuscularly to healthy children aged 6-59.. Influenza a ( H3N2 ) virus hemagglutinins and insect cells: protection against drifted strains ),.! Scanning of hemagglutinin of recent H3N2 influenza viruses than TIV and does not egg-protein! Agreed to the H3 subtype of influenza virus Jung, J. ; Heath A.. You like email updates of new Search results vaccines and hemagglutinin influenza vaccine is urgently needed for prevention and of... 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