title: Pathogenicity and vaccine efficacy of different clades of Asian H5N1 avian influenza A viruses in domestic ducks.
abstract: Waterfowl represent the natural reservoir of all subtypes of influenza A viruses, including H5N1. Ducks are especially considered major contributors to the spread of H5N1 influenza A viruses because they exhibit diversity in morbidity and mortality. Therefore, as a preventive strategy against endemic as well as pandemic influenza, it is important to reduce the spread of H5N1 influenza A viruses in duck populations. Here, we describe the pathogenicity of dominant clades (clades 1 and 2) of H5N1 influenza A viruses circulating in birds in Asia. Four representatives of dominant clades of the viruses cause symptomatic infection but lead to different profiles of lethality in domestic ducks. We also demonstrate the efficacy, cross-protectiveness, and immunogenicity of three different inactivated oil emulsion whole-virus H5 influenza vaccines (derived by implementing reverse genetics) to the viruses in domestic ducks. A single dose of the vaccines containing 1 mug of hemagglutinin protein provides complete protection against a lethal A/Duck/Laos/25/06 (H5N1) influenza virus challenge, with no evidence of morbidity, mortality, or shedding of the challenge virus. Moreover, two of the three vaccines achieved complete cross-clade or cross-subclade protection against the heterologous avian influenza virus challenge. Interestingly, the vaccines induce low or undetectable titers of hemagglutination inhibition (HI), cross-HI, and/or virus neutralization antibodies. The mechanism of complete protection in the absence of detectable antibody responses remains an open question.
authors.affiliation: Department of Infectious Diseases, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105-3678, USA.
authors.forename: Jeong-Ki
authors.initials: JK
authors.lastname: Kim
authors.forename: Patrick
authors.initials: P
authors.lastname: Seiler
authors.forename: Heather L
authors.initials: HL
authors.lastname: Forrest
authors.forename: Alexey M
authors.initials: AM
authors.lastname: Khalenkov
authors.forename: John
authors.initials: J
authors.lastname: Franks
authors.forename: Mahesh
authors.initials: M
authors.lastname: Kumar
authors.forename: William B
authors.initials: WB
authors.lastname: Karesh
authors.forename: Martin
authors.initials: M
authors.lastname: Gilbert
authors.forename: R
authors.initials: R
authors.lastname: Sodnomdarjaa
authors.forename: Bounlom
authors.initials: B
authors.lastname: Douangngeun
authors.forename: Elena A
authors.initials: EA
authors.lastname: Govorkova
authors.forename: Robert G
authors.initials: RG
authors.lastname: Webster
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D000829:Animals, Domestic; D000914:Antibodies, Viral / Q000097:blood; D001208:Asia; D002988:Cloaca / Q000821:virology; D004372:Ducks; D006385:Hemagglutination Inhibition Tests; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology* / Q000472:pathogenicity*; D007252:Influenza Vaccines / Q000276:immunology*; D005585:Influenza in Birds / Q000517:prevention & control* / Q000821:virology*; D009821:Oils / Q000008:administration & dosage; D016019:Survival Analysis; D014132:Trachea / Q000821:virology; D015164:Vaccines, Inactivated / Q000276:immunology; D017201:Virus Shedding
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D007252:Influenza Vaccines; D009821:Oils; D015164:Vaccines, Inactivated
references.citation: Lancet. 2004 Feb 21;363(9409):617-9
references.pmid: 14987888
references.citation: Avian Dis. 2001 Apr-Jun;45(2):355-65
references.pmid: 11417815
references.citation: Avian Dis. 2002 Jan-Mar;46(1):53-63
references.pmid: 11924603
references.citation: Virology. 1983 Sep;129(2):521-3
references.pmid: 6623931
references.citation: J Virol. 2007 Dec;81(23):12911-7
references.pmid: 17881439
references.citation: Microbiol Rev. 1992 Mar;56(1):152-79
references.pmid: 1579108
references.citation: Avian Dis. 1987 Jul-Sep;31(3):498-503
references.pmid: 3118863
references.citation: Virology. 2006 Aug 1;351(2):303-11
references.pmid: 16690097
references.citation: Avian Dis. 2003;47(3 Suppl):951-5
references.pmid: 14575093
references.citation: Virology. 1981 Sep;113(2):712-24
references.pmid: 6267805
references.citation: Virology. 2005 Oct 10;341(1):153-62
references.pmid: 16084554
references.citation: Bull World Health Organ. 1981;59(1):75-8
references.pmid: 6973418
references.citation: Virology. 2003 Sep 30;314(2):580-90
references.pmid: 14554086
references.citation: Vet Microbiol. 2000 May 22;74(1-2):15-27
references.pmid: 10799775
references.citation: Proc Natl Acad Sci U S A. 2000 May 23;97(11):6108-13
references.pmid: 10801978
references.citation: Comp Immunol Microbiol Infect Dis. 1996 Jun;19(3):205-11
references.pmid: 8800546
references.citation: Dev Biol (Basel). 2006;124:61-7
references.pmid: 16447495
references.citation: Emerg Infect Dis. 2006 Jan;12(1):48-54
references.pmid: 16494717
references.citation: Vet Pathol. 1989 Jan;26(1):1-5
references.pmid: 2643840
references.citation: J Gen Virol. 2005 Feb;86(Pt 2):423-433
references.pmid: 15659762
references.citation: Emerg Infect Dis. 2006 Sep;12(9):1319-24
references.pmid: 17073078
references.citation: Lancet. 1998 Feb 14;351(9101):472-7
references.pmid: 9482438
references.citation: J Infect Dis. 2006 Jul 15;194(2):159-67
references.pmid: 16779721
references.citation: Proc Natl Acad Sci U S A. 2005 Jul 26;102(30):10682-7
references.pmid: 16030144
references.citation: J Virol. 1986 May;58(2):655-6
references.pmid: 3701925
references.citation: Science. 2006 Apr 21;312(5772):384-8
references.pmid: 16627734
references.citation: Virology. 1999 Aug 15;261(1):15-9
references.pmid: 10484749
references.citation: Dev Biol (Basel). 2006;124:125-6
references.pmid: 16450453
references.citation: Proc Natl Acad Sci U S A. 2004 Jul 13;101(28):10452-7
references.pmid: 15235128
references.citation: Proc Natl Acad Sci U S A. 2005 Sep 6;102(36):12915-20
references.pmid: 16118277
references.citation: Emerg Infect Dis. 2004 Dec;10(12):2189-91
references.pmid: 15663858
references.citation: Comp Immunol Microbiol Infect Dis. 2009 Jul;32(4):351-63
references.pmid: 18442853
references.citation: Avian Pathol. 2004 Aug;33(4):405-12
references.pmid: 15370037
references.citation: Virology. 1982 Oct 15;122(1):38-47
references.pmid: 6182687
references.citation: Vaccine. 2002 Aug 19;20(25-26):3165-70
references.pmid: 12163268
references.citation: N Engl J Med. 2004 Mar 18;350(12):1179-88
references.pmid: 14985470
references.citation: Avian Dis. 1985 Jul-Sep;29(3):867-72
references.pmid: 4074253
references.citation: Virology. 1999 Feb 1;254(1):115-23
references.pmid: 9927579
references.citation: Virology. 2002 Jan 5;292(1):16-23
references.pmid: 11878904
references.citation: J Virol. 2004 May;78(9):4892-901
references.pmid: 15078970
references.citation: Avian Dis. 2007 Mar;51(1 Suppl):250-9
references.pmid: 17494561
references.citation: Nature. 2004 Jul 8;430(6996):209-13
references.pmid: 15241415
references.citation: Science. 1998 Jan 16;279(5349):393-6
references.pmid: 9430591
references.citation: Emerg Infect Dis. 2006 Feb;12(2):227-34
references.pmid: 16494747
references.citation: J Virol. 2005 Sep;79(17):11269-79
references.pmid: 16103179
references.citation: Nature. 1997 Oct 9;389(6651):554
references.pmid: 9335492
references.citation: Rev Sci Tech. 2000 Aug;19(2):463-82
references.pmid: 10935274
references.citation: J Immunol. 1998 Jan 1;160(1):322-7
references.pmid: 9551987