The avian influenza vaccine Emerflu. Why did it fail?

References

• Alexander DJ. An overview of the epidemiology of avian influenza. Vaccine 2007;25(30):5637-44
   PubMed Web of Science ®Google Scholar
• Tong S, Zhu X, Li Y, et al. New world bats harbor diverse influenza A viruses. PLoS Pathog 2013;9(10):e1003657
   PubMed Web of Science ®Google Scholar
• Kuiken T. Is low pathogenic avian influenza virus virulent for wild waterbirds? Proc Bio Sci 2013;280(1763):20130990
   PubMed Web of Science ®Google Scholar
• Alexander DJ, Brown IH. History of highly pathogenic avian influenza. Rev Sci Tech 2009;28(1):19-38
   PubMed Web of Science ®Google Scholar
• Sonnberg S, Webby RJ, Webster RG. Natural history of highly pathogenic avian influenza H5N1. Virus Res 2013;178(1):63-77
   PubMed Web of Science ®Google Scholar
• Cumulative number of confirmed human cases of avian influenza A(H5N1) reported to WHO. World Health Organization, Geneva, Switzerland. Available from: http://www.who.int/influenza/human_animal_interface/H5N1_cumulative_table_archives/en/ [Last accessed 27 May 2015]
   Google Scholar
• Aditama TY, Samaan G, Kusriastuti R, et al. Risk factors for cluster outbreaks of avian influenza A H5N1 infection, Indonesia. Clin Infect Dis 2011;53(12):1237-44
   PubMed Web of Science ®Google Scholar
• Wang H, Feng Z, Shu Y, et al. Probable limited person-to-person transmission of highly pathogenic avian influenza A (H5N1) virus in China. Lancet 2008;371(9622):1427-34
   PubMed Web of Science ®Google Scholar
• Herfst S, Schrauwen EJ, Linster M, et al. Airborne transmission of influenza A/H5N1 virus between ferrets. Science 2012;336(6088):1534-41
   PubMed Web of Science ®Google Scholar
• Morens DM, Taubenberger JK. Historical thoughts on influenza viral ecosystems, or behold a pale horse, dead dogs, failing fowl, and sick swine. Influenza Other Respir Viruses 2010;4(6):327-37
   PubMed Web of Science ®Google Scholar
• Li C, Hatta M, Nidom CA, et al. Reassortment between avian H5N1 and human H3N2 influenza viruses creates hybrid viruses with substantial virulence. Proc Natl Acad of Sci U S A 2010;107(10):4687-92
   PubMed Web of Science ®Google Scholar
• Worobey M, Han GZ, Rambaut A. A synchronized global sweep of the internal genes of modern avian influenza virus. Nature 2014;508(7495):254-7
   PubMed Web of Science ®Google Scholar
• Global pandemic influenza action plan to increase vaccine supply. WHO/CDS/EPR/GIP/2006.1 The Department of Immunization, Vaccines and Biologicals and the Department of Epidemic and Pandemic Alert and Response. World Health Organization. Geneva, Switzerland. 2006. Available from: http://whqlibdoc.who.int/hq/2006/WHO_IVB_06.13_eng.pdf?ua=1 [Last accessed 27 May 2015]
   Google Scholar
• El Sahly HM, Keitel WA. Pandemic H5N1 influenza vaccine development: an update. Expert Rev Vaccines 2008;7(2):241-7
   PubMed Web of Science ®Google Scholar
• Chen Y, Liang W, Yang S, et al. Human infections with the emerging avian influenza A H7N9 virus from wet market poultry: clinical analysis and characterisation of viral genome. Lancet 2013;381(9881):1916-25
   PubMed Web of Science ®Google Scholar
• Fan S, Zhou L, Wu D, et al. A novel highly pathogenic H5N8 avian influenza virus isolated from a wild duck in China. Influenza Other Respir viruses 2014;8(6):646-53
   PubMed Web of Science ®Google Scholar
• Jennings LC, Monto AS, Chan PK, et al. Stockpiling prepandemic influenza vaccines: a new cornerstone of pandemic preparedness plans. Lancet Infect Dis 2008;8(10):650-8
   PubMed Web of Science ®Google Scholar
• Centers for Disease Control and Prevention. Outbreak of swine-origin influenza A (H1N1) virus infection - Mexico, March-April 2009. MMWR Morb Mortal Wkly Rep 2009;58(17):467-70
   PubMedGoogle Scholar
• World now at the start of 2009 influenza pandemic. World Health Organization. Geneva, Switzerland; 2009. Available from: http://www.who.int/mediacentre/news/statements/2009/h1n1_pandemic_phase6_20090611/en/ [Last accessed 27 May 2015]
   Google Scholar
• Johansen K, Nicoll A, Ciancio BC, Kramarz P. Pandemic influenza A(H1N1) 2009 vaccines in the European Union. Euro surveill 2009;14(41):19361
   PubMedGoogle Scholar
• Borse RH, Shrestha SS, Fiore AE, et al. Effects of vaccine program against pandemic influenza A(H1N1) virus, United States, 2009-2010. Emerg Infect Dis 2013;19(3):439-48
   PubMed Web of Science ®Google Scholar
• Guideline on dossier structure and content for pandemic influenza vaccine marketing authorisation application. EMEA/CPMP/VEG/4717/03- Rev.1 European Medicines Agency, London, UK; 2009. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/10/WC500003993.pdf [Last accessed 27 May 2015]
   Google Scholar
• The mock-up authorisation procedure. European Medicines Agency, London, UK. Available from: http://www.ema.europa.eu/ema/index.jsp?curl=pages/special_topics/q_and_a/q_and_a_detail_000080.jsp [Last accessed 27 May 2015]
   Google Scholar
• Clinical data needed to support the licensure of pandemic influenza vaccines. FDA Guidance for Industry, Washington, DC: Center for Biologics Evaluation and Research 2007. Available from: http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/Vaccines/ucm074786.htm [Last accessed 27 May 2015]
   Google Scholar
• Emerflu withdrawal assessment report. Procedure No. EMEA/H/C/000859. European Medicines Agency, London, UK; 2011. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/Application_withdrawal_assessment_report/2011/03/WC500103511.pdf [Last accessed 27 May 2015]
   Google Scholar
• Wood JM, Robertson JS. From lethal virus to life-saving vaccine: developing inactivated vaccines for pandemic influenza. Nat Rev Microbiol 2004;2(10):842-7
   PubMed Web of Science ®Google Scholar
• Subbarao K, Chen H, Swayne D, et al. Evaluation of a genetically modified reassortant H5N1 influenza A virus vaccine candidate generated by plasmid-based reverse genetics. Virology 2003;305(1):192-200
   PubMed Web of Science ®Google Scholar
• Bresson JL, Perronne C, Launay O, et al. Safety and immunogenicity of an inactivated split-virion influenza A/Vietnam/1194/2004 (H5N1) vaccine: phase I randomised trial. Lancet 2006;367(9523):1657-64
   PubMed Web of Science ®Google Scholar
• Leroux-Roels I, Van der Wielen M, Kafeja F, et al. Humoral and cellular immune responses to split-virion H5N1 influenza vaccine in young and elderly adults. Vaccine 2009;27(49):6918-25
   PubMed Web of Science ®Google Scholar
• Garcia JM, Pepin S, Lagarde N, et al. Heterosubtype neutralizing responses to influenza A (H5N1) viruses are mediated by antibodies to virus haemagglutinin. PLoS One 2009;4(11):e7918
   PubMed Web of Science ®Google Scholar
• Chotpitayasunondh T, Thisyakorn U, Pancharoen C, et al. Safety, humoral and cell mediated immune responses to two formulations of an inactivated, split-virion influenza A/H5N1 vaccine in children. PLoS One 2008;3(12):e4028
   PubMed Web of Science ®Google Scholar
• Hoschler K, Gopal R, Andrews N, et al. Cross-neutralisation of antibodies elicited by an inactivated split-virion influenza A/Vietnam/1194/2004 (H5N1) vaccine in healthy adults against H5N1 clade 2 strains. Influenza Other Respir Viruses 2007;1(5-6):199-206
   PubMed Web of Science ®Google Scholar
• Sanofi Pasteur, a Sanofi Company. Immunogenicity and Safety of an Intramuscular A/H5N1 Inactivated, Split Virion Pandemic Influenza Vaccine in Adults. NCT00545701. National Library of Medicine (US), Bethesda (MD) 2007. Available from: https://clinicaltrials.gov/ct2/show/NCT00545701 [Last accessed 27 May 2015]
   Google Scholar
• Sanofi Pasteur, a Sanofi Company. Safety and Immunogenicity of an Intramuscular A/H5N1 Inactivated, Split Virion Pandemic Influenza Vaccine in Children. NCT00884182. National Library of Medicine (US), Bethesda (MD) 2009. Available from: https://clinicaltrials.gov/ct2/show/NCT00884182 [Last accessed 27 May 2015]
   Google Scholar
• Tsai TF. Fluad(R)-MF59(R)-Adjuvanted Influenza Vaccine in Older Adults. Infect Chemother 2013;45(2):159-74
   PubMedGoogle Scholar
• Rappuoli R, Mandl CW, Black S, De Gregorio E. Vaccines for the twenty-first century society. Nat Rev Immunol 2011;11(12):865-72
   PubMed Web of Science ®Google Scholar
• Van Buynder PG, Konrad S, Van Buynder JL, et al. The comparative effectiveness of adjuvanted and unadjuvanted trivalent inactivated influenza vaccine (TIV) in the elderly. Vaccine 2013;31(51):6122-8
   PubMed Web of Science ®Google Scholar
• Petrovsky N. Vaccine adjuvant safety: the elephant in the room. Expert Rev Vaccines 2013;12(7):715-17
   PubMed Web of Science ®Google Scholar
• Wood JM. Selection of influenza vaccine strains and developing pandemic vaccines. Vaccine 2002;20(Suppl 5):B40-4
   PubMed Web of Science ®Google Scholar
• Arakawa T. Adjuvants: no longer a ’dirty little secret’, but essential key players in vaccines of the future. Expert Rev Vaccines 2011;10(1):1-5
   PubMed Web of Science ®Google Scholar
• Marrack P, McKee AS, Munks MW. Towards an understanding of the adjuvant action of aluminium. Nat Rev Immunol 2009;9(4):287-93
   PubMed Web of Science ®Google Scholar
• Harrison WT. Some Observations on the Use of Alum Precipitated Diphtheria Toxoid. Am J Public Health Nations Health 1935;25(3):298-300
   PubMedGoogle Scholar
• Tetsutani K, Ishii KJ. Adjuvants in influenza vaccines. Vaccine 2012;30(52):7658-61
   PubMed Web of Science ®Google Scholar
• Eisenbarth SC, Colegio OR, O’Connor W, et al. Crucial role for the Nalp3 inflammasome in the immunostimulatory properties of aluminium adjuvants. Nature 2008;453(7198):1122-6
   PubMed Web of Science ®Google Scholar
• Atmar RL, Keitel WA. Adjuvants for pandemic influenza vaccines. Curr Top Microbiol Immunol 2009;333:323-44
   PubMedGoogle Scholar
• Neumann S, Burkert K, Kemp R, et al. Activation of the NLRP3 inflammasome is not a feature of all particulate vaccine adjuvants. Immunol Cell Biol 2014;92(6):535-42
   PubMed Web of Science ®Google Scholar
• Lima HJr, Jacobson LS, Goldberg MF, et al. Role of lysosome rupture in controlling Nlrp3 signaling and necrotic cell death. Cell Cycle 2013;12(12):1868-78
   PubMed Web of Science ®Google Scholar
• Lu B, Nakamura T, Inouye K, et al. Novel role of PKR in inflammasome activation and HMGB1 release. Nature 2012;488(7413):670-4
   PubMed Web of Science ®Google Scholar
• Treanor JJ, Campbell JD, Zangwill KM, et al. Safety and immunogenicity of an inactivated subvirion influenza A (H5N1) vaccine. N Engl J Med 2006;354(13):1343-51
   PubMed Web of Science ®Google Scholar
• Leroux-Roels I, Borkowski A, Vanwolleghem T, et al. Antigen sparing and cross-reactive immunity with an adjuvanted rH5N1 prototype pandemic influenza vaccine: a randomised controlled trial. Lancet 2007;370(9587):580-9
   PubMed Web of Science ®Google Scholar
• Bernstein DI, Edwards KM, Dekker CL, et al. Effects of adjuvants on the safety and immunogenicity of an avian influenza H5N1 vaccine in adults. J Infect Dis 2008;197(5):667-75
   PubMed Web of Science ®Google Scholar
• Calabro S, Tortoli M, Baudner BC, et al. Vaccine adjuvants alum and MF59 induce rapid recruitment of neutrophils and monocytes that participate in antigen transport to draining lymph nodes. Vaccine 2011;29(9):1812-23
   PubMed Web of Science ®Google Scholar
• Khurana S, Chearwae W, Castellino F, et al. Vaccines with MF59 adjuvant expand the antibody repertoire to target protective sites of pandemic avian H5N1 influenza virus. Sci Tran Med 2010;2(15):15ra15
   Google Scholar
• Mosca F, Tritto E, Muzzi A, et al. Molecular and cellular signatures of human vaccine adjuvants. Proc Natl Acad Sci USA 2008;105(30):10501-6
   PubMed Web of Science ®Google Scholar
• Manzoli L, Salanti G, De Vito C, et al. Immunogenicity and adverse events of avian influenza A H5N1 vaccine in healthy adults: multiple-treatments meta-analysis. Lancet Infect Dis 2009;9(8):482-92
   PubMed Web of Science ®Google Scholar
• Layton RC, Gigliotti A, Armijo P, et al. Enhanced immunogenicity, mortality protection, and reduced viral brain invasion by alum adjuvant with an H5N1 split-virion vaccine in the ferret. PloS One 2011;6(6):e20641
   PubMed Web of Science ®Google Scholar
• Ruat C, Caillet C, Bidaut A, et al. Vaccination of macaques with adjuvanted formalin-inactivated influenza A virus (H5N1) vaccines: protection against H5N1 challenge without disease enhancement. J Virol 2008;82(5):2565-9
   PubMed Web of Science ®Google Scholar
• Ninomiya A, Imai M, Tashiro M, Odagiri T. Inactivated influenza H5N1 whole-virus vaccine with aluminum adjuvant induces homologous and heterologous protective immunities against lethal challenge with highly pathogenic H5N1 avian influenza viruses in a mouse model. Vaccine 2007;25(18):3554-60
   PubMed Web of Science ®Google Scholar
• Zhu FC, Wang H, Fang HH, et al. A novel influenza A (H1N1) vaccine in various age groups. N Engl J Med 2009;361(25):2414-23
   PubMed Web of Science ®Google Scholar
• Hem SL, HogenEsch H, Middaugh CR, Volkin DB. Preformulation studies–The next advance in aluminum adjuvant-containing vaccines. Vaccine 2010;28(31):4868-70
   PubMed Web of Science ®Google Scholar
• Hansen B, Sokolovska A, HogenEsch H, Hem SL. Relationship between the strength of antigen adsorption to an aluminum-containing adjuvant and the immune response. Vaccine 2007;25(36):6618-24
   PubMed Web of Science ®Google Scholar
• Hansen B, Belfast M, Soung G, et al. Effect of the strength of adsorption of hepatitis B surface antigen to aluminum hydroxide adjuvant on the immune response. Vaccine 2009;27(6):888-92
   PubMed Web of Science ®Google Scholar
• Noe SM, Green MA, HogenEsch H, Hem SL. Mechanism of immunopotentiation by aluminum-containing adjuvants elucidated by the relationship between antigen retention at the inoculation site and the immune response. Vaccine 2010;28(20):3588-94
   PubMed Web of Science ®Google Scholar
• Fox CB, Kramer RM, Barnes VL, et al. Working together: interactions between vaccine antigens and adjuvants. Ther Advan Vaccines 2013;1(1):7-20
   PubMedGoogle Scholar
• Kool M, Fierens K, Lambrecht BN. Alum adjuvant: some of the tricks of the oldest adjuvant. J Med Microbiol 2012;61(Pt 7):927-34
   PubMed Web of Science ®Google Scholar
• Nolan T, Richmond PC, Formica NT, et al. Safety and immunogenicity of a prototype adjuvanted inactivated split-virus influenza A (H5N1) vaccine in infants and children. Vaccine 2008;26(50):6383-91
   PubMed Web of Science ®Google Scholar
• Wu J, Liu SZ, Dong SS, et al. Safety and immunogenicity of adjuvanted inactivated split-virion and whole-virion influenza A (H5N1) vaccines in children: a phase I-II randomized trial. Vaccine 2010;28(38):6221-7
   PubMed Web of Science ®Google Scholar
• Nolan TM, Richmond PC, Skeljo MV, et al. Phase I and II randomised trials of the safety and immunogenicity of a prototype adjuvanted inactivated split-virus influenza A (H5N1) vaccine in healthy adults. Vaccine 2008;26(33):4160-7
   PubMed Web of Science ®Google Scholar
• Levy O, Goriely S, Kollmann TR. Immune response to vaccine adjuvants during the first year of life. Vaccine 2013;31(21):2500-5
   PubMed Web of Science ®Google Scholar
• Lisciandro JG, Prescott SL, Nadal-Sims MG, et al. Ontogeny of Toll-like and NOD-like receptor-mediated innate immune responses in Papua New Guinean infants. PloS One 2012;7(5):e36793
   PubMed Web of Science ®Google Scholar
• Couch RB, Decker WK, Utama B, et al. Evaluations for in vitro correlates of immunogenicity of inactivated influenza a H5, H7 and H9 vaccines in humans. PLoS ONE 2012;7(12):e50830
   PubMed Web of Science ®Google Scholar
• Bright RA, Carter DM, Crevar CJ, et al. Cross-clade protective immune responses to influenza viruses with H5N1 HA and NA elicited by an influenza virus-like particle. PloS One 2008 3(1):e1501-2008
   Google Scholar
• Geeraedts F, Goutagny N, Hornung V, et al. Superior immunogenicity of inactivated whole virus H5N1 influenza vaccine is primarily controlled by Toll-like receptor signalling. PLoS Pathog 2008;4(8):e1000138
   PubMed Web of Science ®Google Scholar
• Hovden AO, Cox RJ, Haaheim LR. Whole influenza virus vaccine is more immunogenic than split influenza virus vaccine and induces primarily an IgG2a response in BALB/c mice. Scandinavian J Immunol 2005;62(1):36-44
   PubMed Web of Science ®Google Scholar
• Bungener L, Geeraedts F, Ter Veer W, et al. Alum boosts TH2-type antibody responses to whole-inactivated virus influenza vaccine in mice but does not confer superior protection. Vaccine 2008;26(19):2350-9
   PubMed Web of Science ®Google Scholar
• Lin J, Zhang J, Dong X, et al. Safety and immunogenicity of an inactivated adjuvanted whole-virion influenza A (H5N1) vaccine: a phase I randomised controlled trial. Lancet 2006;368(9540):991-7
   PubMed Web of Science ®Google Scholar
• Wu J, Fang HH, Chen JT, et al. Immunogenicity, safety, and cross-reactivity of an inactivated, adjuvanted, prototype pandemic influenza (H5N1) vaccine: a phase II, double-blind, randomized trial. Clin Infect Dis 2009;48(8):1087-95
   PubMed Web of Science ®Google Scholar
• Ehrlich HJ, Muller M, Oh HM, et al. A clinical trial of a whole-virus H5N1 vaccine derived from cell culture. N Engl J Med 2008;358(24):2573-84
   PubMed Web of Science ®Google Scholar
• Reber A, Katz J. Immunological assessment of influenza vaccines and immune correlates of protection. Expert Rev Vaccines 2013;12(5):519-36
   PubMed Web of Science ®Google Scholar
• Baz M, Luke CJ, Cheng X, et al. H5N1 vaccines in humans. Virus Res 2013;178(1):78-98
   PubMed Web of Science ®Google Scholar
• Plans-Rubio P. The vaccination coverage required to establish herd immunity against influenza viruses. Prev Med 2012;55(1):72-7
   PubMed Web of Science ®Google Scholar
• Stephenson I. H5N1 vaccines: how prepared are we for a pandemic? Lancet 2006;368(9540):965-6
   PubMed Web of Science ®Google Scholar
• Jia N, Wang SX, Liu YX, et al. Increased sensitivity for detecting avian influenza-specific antibodies by a modified hemagglutination inhibition assay using horse erythrocytes. J Virol Methods 2008;153(1):43-8
   PubMed Web of Science ®Google Scholar
• Noah DL, Hill H, Hines D, et al. Qualification of the hemagglutination inhibition assay in support of pandemic influenza vaccine licensure. Clin Vaccine Immunol 2009;16(4):558-66
   PubMed Web of Science ®Google Scholar
• Kayali G, Setterquist SF, Capuano AW, et al. Testing human sera for antibodies against avian influenza viruses: horse RBC hemagglutination inhibition vs. microneutralization assays. J Clin Virol 2008;43(1):73-8
   PubMed Web of Science ®Google Scholar
• Low JG, Lee LS, Ooi EE, et al. Safety and immunogenicity of a virus-like particle pandemic influenza A (H1N1) 2009 vaccine: results from a double-blinded, randomized Phase I clinical trial in healthy Asian volunteers. Vaccine 2014;32(39):5041-8
   PubMed Web of Science ®Google Scholar
• Schneider-Ohrum K, Giles BM, Weirback HK, et al. Adjuvants that stimulate TLR3 or NLPR3 pathways enhance the efficiency of influenza virus-like particle vaccines in aged mice. Vaccine 2011;29(48):9081-92
   PubMed Web of Science ®Google Scholar
• Didierlaurent AM, Morel S, Lockman L, et al. AS04, an aluminum salt- and TLR4 agonist-based adjuvant system, induces a transient localized innate immune response leading to enhanced adaptive immunity. J Immunol 2009;183(10):6186-97
   PubMed Web of Science ®Google Scholar
• Lee YN, Kim MC, Lee YT, et al. AS04-adjuvanted virus-like particles containing multiple M2 extracellular domains of influenza virus confer improved protection. Vaccine 2014;32(35):4578-85
   PubMed Web of Science ®Google Scholar