The mechanism of action of FluBlok is the same as that of the licensed egg‐grown trivalent inactivated influenza vaccines (TIV), thereby simplifying the regulatory pathway for product approval. Traditional flu vaccine targets the globular head of HA to prevent the virus from binding to human cells. Abstract FluBlok, a recombinant trivalent hemagglutinin (HA) vaccine produced in insect cell culture using the baculovirus expression system, provides an attractive alternative to the current … ; Albrecht, R.; Blum, D.L. 2020 Aug 26;5:77. doi: 10.1038/s41541-020-00227-x. Whittle, J.R.; Zhang, R.; Khurana, S.; King, L.R. Improved Titers against Influenza Drift Variants with a Nanoparticle Vaccine. 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 … Conventional influenza virus vaccines induce strain-specific neutralizing antibodies against the variable immunodominant globular head domain of … Science, 349, 1301–1306. b. The HA trimer was also truncated to exclude the stem region and reduce computation time. ; Moody, M.A. HA2 has much less probability of antigenic variation co… 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. ; Metlagel, Z.; Bujny, M.V. Potent anti-influenza H7 human monoclonal antibody induces separation of hemagglutinin receptor-binding head domains. Wiley, D.C.; Wilson, I.A. The only effective measure to decrease morbidity and mortality caused by the influenza virus in the human population is worldwide vaccination. ; Stevens, J. Simonsen, L.; Clarke, M.J.; Williamson, G.D.; Stroup, D.F. Treanor JJ, El Sahly H, King J, Graham I, Izikson R, Kohberger R, Patriarca P, Cox M. Vaccine. ; Kwaks, T.; Zuijdgeest, D.; Khayat, R.; Ekiert, D.C.; Lee, J.H. Sorzano, C.O. The whole trick lies on … ; Li, Y.; et al. The tested chimeric haemagglutinin-based, universal influenza virus vaccine regimens elicited cross-reactive serum IgG antibodies that targeted the conserved haemagglutinin stalk domain. Abstract. Influenza immunization elicits antibodies specific for an egg-adapted vaccine strain. ; Alabi, N.; Barnes, J.; Biggerstaff, M.; Brammer, L.; Budd, A.P. Influenza vaccines usually encourage the body to produce antibodies that target the globular head domain, or tip, of the protein. ; Augustine, A.D.; Ferguson, S.; Paules, C.I. Interestingly A2.91.3 recovered binding to T160K/L194P egg-derived mutant compared to the L194P mutation alone in A/Hong Kong/4801/2014 HA (, The VE subdomain antibody A2.4.1 had broad neutralization (, Classical hemagglutinin inhibition (HAI) assays largely depend upon RBS targeting antibodies to block red blood cell (RBC) agglutination. The emergence of the swine-origin 2009 influenza pandemic illustrates the need for improved vaccine production and delivery strategies. ; Palm, A.E. A universal vaccine against influenza remains a critical target, and efforts have recently focused on the stem of the hemagglutinin glycoprotein. Improved influenza countermeasures require basic research on how viruses enter cells, replicate, mutate, evolve into new strains and induce an immune response. ; Skehel, J.J. Together, this study describes Mab-induced destabilization of the influenza HA stem domain, faster kinetics of influenza virus fusion, and ERD in vivo. Chimeric hemagglutinin influenza virus vaccine constructs elicit broadly protective stalk-specific antibodies J. Virol. ; Wood, J.; Heath, A.; Katz, J.M. ; Graham, B.S. Please enable it to take advantage of the complete set of features! Influenza vaccines usually encourage the body to … Erbelding, E.J. Influenza virus surface glycoprotein hemagglutinin (HA) is an excellent and chief target that elicits neutralizing antibodies during vaccination or natural infection. ; Ohshima, N.; Stanfield, R.L. A stable trimeric influenza hemagglutinin stem as a broadly protective immunogen. ; 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. Influenza Virus Vaccination Elicits Poorly Adapted B Cell Responses in Elderly Individuals. ; O’Neil, R.E. , 87 ( 2013 ) , pp. Vacunas. Therefore, inactivated quadrivalent influenza vaccines are standardized to contain the hemagglutinin of influenza virus strains (two subtypes A and two types B), representing the influenza viruses likely to be circulating in the United States in the upcoming influenza … MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Broadly neutralizing hemagglutinin stalk-specific antibodies require FcgammaR interactions for protection against influenza virus in vivo. Received: 21 January 2020 / Revised: 17 February 2020 / Accepted: 18 February 2020 / Published: 22 February 2020. FluBlok, a recombinant influenza vaccine. This site needs JavaScript to work properly. These help in developing influenza countermeasures such as vaccines, therapies and diagnostic tools. Vaccines (Basel). FluBlok, a next generation influenza vaccine manufactured in insect cells. The funder had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.  |  Centers for Disease Control (CDC) . Popova, L.; Smith, K.; West, A.H.; Wilson, P.C. Lander, G.C. 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. ; Fruhwirth, A.; McDaniel, J.R.; Jung, J.; Boutz, D.R. 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/. Clin Diagn Lab Immunol 1996; 3:507–510. ; Yu, W.; Iba, Y.; Okuno, Y.; Kurosawa, Y.; Wilson, I.A. SARS-CoV-2 vaccines in advanced clinical trials: Where do we stand? ; Wu, N.C.; Hensley, S.E. ; Brenner, S.E. We thank Kelsey Jacobson, Michelle Walker, Chineye Emeche, Malgorzata Wisniewska, Jim Norton, Zachary Longacre, Rafia Khatoon, Stefanie Kluepfel-Stahl, and Betty Ekechukwu for technical assistance with reagents and assays. Immunodominance and Antigenic Variation of Influenza Virus Hemagglutinin: Implications for Design of Universal Vaccine Immunogens. Epub 2011 Jan 28. A universal vaccine against influenza remains a critical target, and efforts have recently focused on the stem of the hemagglutinin glycoprotein. Wild-type and egg passage HA sequences were compared to published sequences in the GISAID EpiFlu database. Impagliazzo, A.F., et al., 2015. https://www.drugs.com/ppa/influenza-virus-vaccine-recombinant.html ; Glenn, G. Novel hemagglutinin nanoparticle influenza vaccine with Matrix-M adjuvant induces hemagglutination inhibition, neutralizing, and protective responses in ferrets against homologous and drifted A(H3N2) subtypes. Previous studies on potential influenza vaccines showed that vaccine based only on influenza virus NP proved unusable. Paules, C.I. Its HA2 subunit (stem domain) is most conserved as compared to HA1 subunit (globular head domain). Current vaccines are effective but strain specific due to their focus on the … A Site of Vulnerability on the Influenza Virus Hemagglutinin Head Domain Trimer Interface. Keitel WA, Couch RB, Cate TR et al. A stark example is the pandemic of 1918, in which an estimated 50 to 100 million people were killed (5). Broadly neutralizing human antibody that recognizes the receptor-binding pocket of influenza virus hemagglutinin. Deep mutational scanning of hemagglutinin helps predict evolutionary fates of human H3N2 influenza variants. 2011. These antibodies against flu have been found to act by two different mechanisms, mirroring the dual functions of hemagglutinin: Online ahead of print. Please cite this paper as: Getie‐Kebtie et al. -. -, Keitel WA, Cate TR, Atmar RL et al. 2009 Nov 5;27(47):6589-94. doi: 10.1016/j.vaccine.2009.08.032. J Clin Microbiol 1994; 32:2468–2473. 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. 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 Vestigial Esterase Domain of Haemagglutinin of H5N1 Avian Influenza A Virus: Antigenicity and Contribution to Viral Pathogenesis. ; Cobey, S.; Hensley, S.E.  |  2009 Jun;37(3):182-9. doi: 10.1016/j.biologicals.2009.02.014. Evaluation of the safety, reactogenicity and immunogenicity of FluBlok® trivalent recombinant baculovirus-expressed hemagglutinin influenza vaccine administered intramuscularly to healthy adults 50-64 years of age. ; Haynes, B.F.; Walter, E.B. DiLillo, D.J. Vaccine. The statements, opinions and data contained in the journal, © 1996-2021 MDPI (Basel, Switzerland) unless otherwise stated. The HI test works by measuring how well antibodies bind to (and thus … ; project administration, N.P., M.J.M., V.S., G.M.G., and G.S. (2012) Label‐free mass spectrometry‐based quantification of hemagglutinin and neuraminidase in influenza virus preparations and vaccines. New strategies for the development of H5N1 subtype influenza vaccines: progress and challenges. Smith, G.; Liu, Y.; Flyer, D.; Massare, M.J.; Zhou, B.; Patel, N.; Ellingsworth, L.; Lewis, M.; Cummings, J.F. ; King, H.G. Virus neutralizing activity was determined using a WHO-recommended neutralization assay [, Electron microscopy was performed by NanoImaging Services (San Diego, CA, USA) with an FEI Tecnai T12 electron microscope operating at 120 keV equipped with an FEI Eagle 4k × 4k CCD camera. ; Dormitzer, P.R. Maier, J.K.; Labute, P. Assessment of fully automated antibody homology modeling protocols in molecular operating environment. Zost, S.J. 26. ; Steel, J.; Rubrum, A.; Bhabha, G.; Khayat, R.; Lee, J.H. ; et al. Localization of epitopes recognized by monoclonal antibodies that neutralized the H3N2 influenza viruses in man. ; Kaplan, B.S. Please note that many of the page functionalities won't work as expected without javascript enabled. Appion: An integrated, database-driven pipeline to facilitate EM image processing. Due to the lack of preformed immunity against the major viral antigen (hemagglutinin [HA]), pandemic influenza can affect more than 50% of the population in a single year and often causes more severe disease than epidemic influenza. It is a trivalent recombinant hemagglutinin (HA) vaccine, produced by Protein Sciences Corporation, that contains HA antigen derived from three influenza virus … Lee, J.M. ; Zhu, X.; Kose, N.; Bombardi, R.; Finn, J.A. Hemagglutinin (HA) is the major antigen in influenza vaccines, and glycosylation is known to influence its antigenicity. Gilbert, B.E. ; Wilson, I.A. ; Pascual-Montano, A. XMIPP: A new generation of an open-source image processing package for electron microscopy. ; Huffman, C.J. Lee, P.S. 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. Licensed seasonal influenza vaccines include inactivated, live attenuated, and recombinant vaccines [5, 6]. eCollection 2020. Commercial antibodies F045-092, F005-126, and CR8020 (Creative Biolabs, Shirley, NY, USA) and hybridoma derived murine antibodies were bound sequentially (5 μg/mL) for 300 sec each and binding normalized to buffer control without competition (100%). The trivalent (IIV3) and quadrivalent (IIV4) inactivated influenza vaccines … Reed, C.; Chaves, S.S.; Daily Kirley, P.; Emerson, R.; Aragon, D.; Hancock, E.B. Epub 2011 Aug 9. Background Influenza vaccination is the primary method for preventing influenza and its severe complications. Recombinant HA-based vaccine outperforms split and subunit vaccines in elicitation of influenza-specific CD4 T cells and CD4 T cell-dependent antibody responses in humans. Morbidity and Mortality Weekly Report (MMWR) 2002; 51:1–31. Las vacunas de la gripe basadas en las partículas. ; Jiang, T.; Wang, Y.D. ; Kent, S.J. ; Carazo, J.M. ; Kaur, K.; Andrews, S.F. 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. 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. 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. 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). ; formal analysis, A.D.P., N.P., H.Z., and B.Z. Support of this work was provided by Novavax, Inc. 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 … ; Voss, T.G. Lee, P.S. In this issue of Cell and a related Cell Host & Microbe article, three studies identify broad protective epitopes in the hemagglutinin … Previously, a novel hemagglutinin (HA) for H5N1 influenza was derived from a methodology termed computationally optimized broadly reactive antigen (COBRA). Epitope analysis for influenza vaccine design. Impact of influenza vaccination on seasonal mortality in the US elderly population. To address these limitations, we have developed a hemagglutinin (HA)-based protein-detergent nanoparticle influenza vaccine (NIV) with a saponin-based Matrix-M™ adjuvant. 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. ; Tan, Y.J. ; Dillon, M.A. Influenza virus infections are a major public health concern and cause significant morbidity and mortality worldwide. ; investigation, A.D.P., N.P., H.Z., and B.Z. Ekiert, D.C.; Kashyap, A.K. Cross-neutralization of influenza A viruses mediated by a single antibody loop. Hemagglutinin (Influenza) The influenza hemagglutinin is the prototype of the class I proteins, which so far have been found in orthomyxoviruses, paramyxoviruses, retroviruses, and filoviruses (Dutch et al., 2000; Skehel and Wiley, 1998; Weissenhorn et al., 1999). ; Bowman, C.A. ; Post, D.J. These interests do not alter the authors’ adherence to policies on sharing data and materials. ; Deem, M.W. Highlight: Influenza vaccine needs to be administered … Please let us know what you think of our products and services. Naturally occurring antibodies in humans can neutralize a variety of influenza virus strains, including H3, H1, H2, and H5. Influenza Other Respir Viruses. Current influenza virus vaccines mostly target the immunodominant head domain of the viral hemagglutinin (HA) and are therefore strain specific 8. Xu, X.; Blanton, L.; Elal, A.I.A. Ekiert, D.C.; Friesen, R.H.; Bhabha, G.; Kwaks, T.; Jongeneelen, M.; Yu, W.; Ophorst, C.; Cox, F.; Korse, H.J. ; et al. Skin-based immunization represents an attractive alternative to traditional hypodermic needle vaccination routes. ; Hon, G.; Chandonia, J.M. Structure and receptor binding preferences of recombinant human A(H3N2) virus hemagglutinins. ; Crowe, J.E., Jr.; Wilson, I.A. Okada, J.; Ohshima, N.; Kubota-Koketsu, R.; Iba, Y.; Ota, S.; Takase, W.; Yoshikawa, T.; Ishikawa, T.; Asano, Y.; Okuno, Y.; et al. ; et al. Update: Influenza Activity in the United States During the 2018-19 Season and Composition of the 2019-20 Influenza Vaccine. FluBlok, a trivalent recombinant hemagglutinin (rHA) vaccine, is under development by Protein Sciences Corporation. The conserved stalk of the viral hemagglutinin has been identified as potential target antigen for this new generation of vaccines.

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