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. Epub 2012 Nov 23. ; Voss, T.G. The trivalent (IIV3) and quadrivalent (IIV4) inactivated influenza vaccines … ; et al. MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Lee, P.S. ; Gilchuk, P.; Matta, P.; Zhu, X.; Lang, S.; Nieusma, T.; et al. Highlight: Influenza vaccine needs to be administered … ; et al. Iba, Y.; Fujii, Y.; Ohshima, N.; Sumida, T.; Kubota-Koketsu, R.; Ikeda, M.; Wakiyama, M.; Shirouzu, M.; Okada, J.; Okuno, Y.; et al. Epub 2020 Jul 9. Vaccine. These antibodies often have … 2009 Nov 5;27(47):6589-94. doi: 10.1016/j.vaccine.2009.08.032. Cross-neutralization of influenza A viruses mediated by a single antibody loop. FluBlok, a recombinant influenza vaccine. The A2.91.3 Fv domain was defined as the ligand with the HC CDR3 residues (YYYYD) used for the ligand site. Turner, H.L. -, Huber VC, JA Cullers. Conceptualization, A.D.P, N.P., M.J.M., G.M.G., and G.S. Vacunas. FluBlok contains three times more HA than TIV and does not contain egg-protein or preservatives. We developed novel chimeric hemagglutinin (cHA)-based universal influenza virus vaccines, which contain a conserved HA stalk domain from a 2009 pandemic H1N1 (pH1N1) strain … The tested chimeric haemagglutinin-based, universal influenza virus vaccine regimens elicited cross-reactive serum IgG antibodies that targeted the conserved haemagglutinin stalk domain. Morbidity and Mortality Weekly Report (MMWR) 2002; 51:1–31. 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). Science, 349, 1301–1306. Traditional flu vaccine targets the globular head of HA to prevent the virus from binding to human cells. A unique and conserved neutralization epitope in H5N1 influenza viruses identified by an antibody against the A/Goose/Guangdong/1/96 hemagglutinin. Lee, P.S. 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. 25. Keitel WA, Couch RB, Cate TR et al. Find support for a specific problem on the support section of our website. All authors have read and agreed to the published version of the manuscript. ; Kwaks, T.; Zuijdgeest, D.; Khayat, R.; Ekiert, D.C.; Lee, J.H.  |  ; Li, X.F. 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. Please cite this paper as: Getie‐Kebtie et al. Lee, J.; Paparoditis, P.; Horton, A.P. The Brighton Collaboration standardized template for collection of key information for benefit-risk assessment of protein vaccines. New strategies for the development of H5N1 subtype influenza vaccines: progress and challenges. ; Spindler, M.; Lindner, E.; Hahn, T.; Plested, J.; et al. Epub 2009 Aug 27. WebLogo: A sequence logo generator. 6542 - 6550 View Record in Scopus Google Scholar ; Brandenburg, B.; et al. Chimeric hemagglutinin vaccine elicits broadly protective CD4 and CD8 T cell responses against multiple influenza strains and subtypes Hsin-Yu Liao , Shih-Chi Wang , Yi-An Ko , Kuo-I Lin , Che … 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. Abstract. Lander, G.C. 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. Embryonated hen eggs are traditionally used for influenza vaccine production, but vaccines produced in mammalian and insect cells were recently licensed. Protective efficacy of a trivalent recombinant hemagglutinin protein vaccine (FluBlok®) against influenza in healthy adults: a randomized, placebo-controlled trial. ; Engelhardt, O.G. Biologicals. Simonsen, L.; Reichert, T.A. Epub 2009 Mar 17. Development of Universal Influenza Vaccines Targeting Conserved Viral Proteins. The Vestigial Esterase Domain of Haemagglutinin of H5N1 Avian Influenza A Virus: Antigenicity and Contribution to Viral Pathogenesis. ; Tan, Y.J. 2019 Nov 1;7(4):169. doi: 10.3390/vaccines7040169. 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. ; Thompson, L.F.; Air, G.M. 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 … ; Skehel, J.J. Platforms based on virus culture in mammalian or insect cells are currently under investigation. A Site of Vulnerability on the Influenza Virus Hemagglutinin Head Domain Trimer Interface. Persistent Antibody Clonotypes Dominate the Serum Response to Influenza over Multiple Years and Repeated Vaccinations. ACIP. ; Viboud, C.; Blackwelder, W.C.; Taylor, R.J.; Miller, M.A. Immunodominance of antigenic site B over site A of hemagglutinin of recent H3N2 influenza viruses. ; Pallesen, J.; Lang, S.; Bangaru, S.; Urata, S.; Li, S.; Cottrell, C.A. The virus is spread through aerosolized respiratory droplets during Alternatively, expression of fragments of the hemagglutinin (HA) protein in prokaryotic systems can potentially be the most efficacious strategy for … Erbelding, E.J. NLM ; 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. These vaccines elicit antibodies that target the surface viral glycoproteins hemagglutinin and neuraminidase. DiLillo, D.J. 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. 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. USA.gov. Chambers, B.S. A Single Amino Acid Substitution at Residue 218 of Hemagglutinin Improves the Growth of Influenza A(H7N9) Candidate Vaccine Viruses J Virol. 2020 Jul 31;38(35):5734-5739. doi: 10.1016/j.vaccine.2020.06.044. Chakraborty S, Mallajosyula V, Tato CM, Tan GS, Wang TT. Our dedicated information section provides allows you to learn more about MDPI. ; Kent, S.J. Simonsen, L.; Clarke, M.J.; Williamson, G.D.; Stroup, D.F. Its HA2 subunit (stem domain) is most conserved as compared to HA1 subunit (globular head domain). Subjects were randomized to receive one of the following vaccination regimens: trivalent hemagglutinin (HA) DNA prime followed by trivalent inactivated influenza vaccine (IIV3) boost with a 3.5 month interval (DNA-IIV3), IIV3 prime followed by IIV3 boost with a 10 month interval (IIV3-IIV3), or concurrent DNA and IIV3 prime followed by IIV3 boost with a 10 month interval (DNA/IIV3-IIV3). ; Huddleston, J.; Doud, M.B. ; Peiris, M.; Hoschler, K.; Hungnes, O.; Zhang, W.; Van Kerkhove, M.D. Reed, C.; Chaves, S.S.; Daily Kirley, P.; Emerson, R.; Aragon, D.; Hancock, E.B. ; Kaplan, B.S. The strain specificity of vaccines presently in use mirrors the exquisite specificity of the neutralizing antibodies that they induce, that is, antibodies which bind to the highly variable globular … Vaccine 19:1732–1737 . Xu, R.; Krause, J.C.; McBride, R.; Paulson, J.C.; Crowe, J.E., Jr.; Wilson, I.A. Raymond, D.D. Introduction. Whittle, J.R.; Zhang, R.; Khurana, S.; King, L.R. You seem to have javascript disabled. ; Faynboym, A.M.; et al. Background Influenza vaccination is the primary method for preventing influenza and its severe complications. ; Chen, Y.Q. The development of anti-IAV vaccines and therapeutics is urgently needed for prevention and treatment of IAV infection and for controlling future influenza pandemics. Maier, J.K.; Labute, P. Assessment of fully automated antibody homology modeling protocols in molecular operating environment. ; resources, J.-H.T., and V.S. Data analysis was performed with Octet Data Analysis HT 10.0 software using the Epitope Binning. Wu, N.C.; Zost, S.J. 9,10 High-dose vaccine … ; Steel, J.; Rubrum, A.; Bhabha, G.; Khayat, R.; Lee, J.H. A stark example is the pandemic of 1918, in which an estimated 50 to 100 million people were killed (5). FluBlok, a trivalent recombinant hemagglutinin (rHA) vaccine, is under development by Protein Sciences Corporation. ; Gilchuk, P.; et al. ; Tan, G.S. Structure and receptor binding preferences of recombinant human A(H3N2) virus hemagglutinins. King JC Jr, Cox MM, Reisinger K, Hedrick J, Graham I, Patriarca P. Vaccine. ; Yu, W.; McBride, R.; Paulson, J.C.; Yuen, K.Y. Authors A.D.P., N.P., M.J.M., H.Z., J.-H.T., B.Z., V.S., G.M.G., and G.S. These help in developing influenza countermeasures such as vaccines, therapies and diagnostic tools. Belongia, E.A. Vaccination produces neutralizing antibodies that target the HA1 subunit of the HA (hemagglutinin) protein and are strain specific. ; Alby, K.; Hensley, S.E. RIV4 = Quadrivalent Recombinant Influenza Vaccine. Current influenza virus vaccines mostly target the immunodominant head domain of the viral hemagglutinin (HA) and are therefore strain specific 8. Chimeric hemagglutinin influenza virus vaccine constructs elicit broadly protective stalk-specific antibodies J. Virol. Richards KA, Moritzky S, Shannon I, Fitzgerald T, Yang H, Branche A, Topham DJ, Treanor JJ, Nayak J, Sant AJ. Influenza vaccines usually encourage the body to produce antibodies that target the globular head domain, or tip, of the protein. those of the individual authors and contributors and not of the publisher and the editor(s). BioDrugs 25:285–298 . ; Dormitzer, P.R. ; Haynes, B.F.; Walter, E.B. Gilbert, B.E. Centers for Disease Control (CDC) . Vaccines (Basel). Influenza vaccines usually encourage the body to … ; Deem, M.W. , 87 ( 2013 ) , pp. FluBlok contains three times more HA t … In a phase 1 clinical trial of older adults, the vaccine demonstrated broadly cross-reactive A (H3N2) HA antibody responses. ; Voss, N.R. The statements, opinions and data contained in the journals are solely Influenza vaccine efficacy and regulatory approval depends on the HAI assay although it only captures a limited subset of serum antibodies. (2012) Label‐free mass spectrometry‐based quantification of hemagglutinin and neuraminidase in influenza virus preparations and vaccines. A key aspect of future influenza vaccine antigen development, therefore, will be both the retention of the highly efficacious, but also highly strain-specific, immune responses evoked by current vaccines; complemented by induction of responses to highly conserved neutralizing epitopes which may be found not only in the stem, but also the head, of hemagglutinin [. , W.C. ; Taylor, R.J. ; Miller, M.A neutral with regard to jurisdictional claims in published and. Set of features as expected without javascript enabled ; Bilbao-Castro, J.R. ; Jung J.. 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