title: A live attenuated H7N7 candidate vaccine virus induces neutralizing antibody that confers protection from challenge in mice, ferrets, and monkeys.
abstract: A live attenuated H7N7 candidate vaccine virus was generated by reverse genetics using the modified hemagglutinin (HA) and neuraminidase (NA) genes of highly pathogenic (HP) A/Netherlands/219/03 (NL/03) (H7N7) wild-type (wt) virus and the six internal protein genes of the cold-adapted (ca) A/Ann Arbor/6/60 ca (AA ca) (H2N2) virus. The reassortant H7N7 NL/03 ca vaccine virus was temperature sensitive and attenuated in mice, ferrets, and African green monkeys (AGMs). Intranasal (i.n.) administration of a single dose of the H7N7 NL/03 ca vaccine virus fully protected mice from lethal challenge with homologous and heterologous H7 viruses from Eurasian and North American lineages. Two doses of the H7N7 NL/03 ca vaccine induced neutralizing antibodies in serum and provided complete protection from pulmonary replication of homologous and heterologous wild-type H7 challenge viruses in mice and ferrets. One dose of the H7N7 NL/03 ca vaccine elicited an antibody response in one of three AGMs that was completely protected from pulmonary replication of the homologous wild-type H7 challenge virus. The contribution of CD8(+) and/or CD4(+) T cells to the vaccine-induced protection of mice was evaluated by T-cell depletion; T lymphocytes were not essential for the vaccine-induced protection from lethal challenge with H7 wt viruses. Additionally, passively transferred neutralizing antibody induced by the H7N7 NL/03 ca virus protected mice from lethality following challenge with H7 wt viruses. The safety, immunogenicity, and efficacy of the H7N7 NL/03 ca vaccine virus in mice, ferrets, and AGMs support the evaluation of this vaccine virus in phase I clinical trials.
authors.affiliation: LID, NIAID, NIH, Bethesda, MD 20892, USA.
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Min
authors.forename: Leatrice
authors.initials: L
authors.lastname: Vogel
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Matsuoka
authors.forename: Bin
authors.initials: B
authors.lastname: Lu
authors.forename: David
authors.initials: D
authors.lastname: Swayne
authors.forename: Hong
authors.initials: H
authors.lastname: Jin
authors.forename: George
authors.initials: G
authors.lastname: Kemble
authors.forename: Kanta
authors.initials: K
authors.lastname: Subbarao
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology*; D000914:Antibodies, Viral / Q000276:immunology; D002642:Chick Embryo; D002645:Chickens; D002522:Chlorocebus aethiops; D004195:Disease Models, Animal; D005260:Female; D005289:Ferrets; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D006801:Humans; D053126:Influenza A Virus, H7N7 Subtype / Q000276:immunology; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology* / Q000517:prevention & control* / Q000821:virology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009439:Neuraminidase / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics / Q000276:immunology; D014764:Viral Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D014613:Vaccines, Attenuated; D014764:Viral Proteins; C483468:hemagglutinin, human influenza A virus; C487630:NA protein, influenza A virus; D009439:Neuraminidase
references.citation: Vaccine. 2008 Mar 25;26(14):1742-50
references.pmid: 18336962
references.citation: J Virol. 2003 Dec;77(24):13399-402
references.pmid: 14645595
references.citation: Proc Natl Acad Sci U S A. 2004 Feb 3;101(5):1356-61
references.pmid: 14745020
references.citation: Virology. 2008 Aug 15;378(1):123-32
references.pmid: 18585748
references.citation: Cell. 1987 Aug 28;50(5):665-6
references.pmid: 3304656
references.citation: Vaccine. 2004 Oct 22;22(31-32):4137-8
references.pmid: 15474703
references.citation: MMWR Morb Mortal Wkly Rep. 2004 Jul 2;53(25):547-52
references.pmid: 15229411
references.citation: Vaccine. 2003 Oct 1;21(27-30):4430-6
references.pmid: 14505926
references.citation: J Virol. 2007 Oct;81(19):10558-66
references.pmid: 17634234
references.citation: Virology. 1981 Sep;113(2):725-35
references.pmid: 7023022
references.citation: J Virol. 2010 Feb;84(3):1289-301
references.pmid: 19906920
references.citation: Vaccine. 2009 Jun 8;27(28):3744-53
references.pmid: 19464558
references.citation: Vaccine. 2009 Mar 18;27(13):1889-97
references.pmid: 19368768
references.citation: Virology. 2003 Feb 1;306(1):18-24
references.pmid: 12620793
references.citation: Proc Natl Acad Sci U S A. 2000 May 23;97(11):6108-13
references.pmid: 10801978
references.citation: Arch Virol. 2000;145(5):1047-58
references.pmid: 10881690
references.citation: Influenza Other Respir Viruses. 2007 Jul;1(4):157-66
references.pmid: 19432631
references.citation: Nat Rev Immunol. 2007 Apr;7(4):267-78
references.pmid: 17363960
references.citation: Emerg Infect Dis. 2004 Dec;10(12):2196-9
references.pmid: 15663860
references.citation: Virus Res. 1997 Jun;49(2):173-86
references.pmid: 9213392
references.citation: J Infect Dis. 2009 Mar 1;199(5):711-6
references.pmid: 19210163
references.citation: Vet Pathol. 1994 Mar;31(2):237-45
references.pmid: 8203087
references.citation: Emerg Infect Dis. 2006 Jan;12(1):66-72
references.pmid: 16494720
references.citation: Vaccine. 2009 Aug 6;27(36):4953-60
references.pmid: 19540952
references.citation: Emerg Infect Dis. 2004 Apr;10(4):693-9
references.pmid: 15200862
references.citation: Lancet. 1996 Sep 28;348(9031):901-2
references.pmid: 8826845
references.citation: J Virol. 2005 Oct;79(19):12401-7
references.pmid: 16160167
references.citation: Virology. 2009 Dec 20;395(2):280-8
references.pmid: 19833372
references.citation: Clin Vaccine Immunol. 2007 Nov;14(11):1425-32
references.pmid: 17913860
references.citation: N Engl J Med. 2008 Jan 17;358(3):261-73
references.pmid: 18199865
references.citation: Lancet. 2004 Feb 21;363(9409):587-93
references.pmid: 14987882
references.citation: J Immunol. 1997 Feb 1;158(3):1222-30
references.pmid: 9013963
references.citation: PLoS Med. 2006 Sep;3(9):e360
references.pmid: 16968127
references.citation: Curr Opin Infect Dis. 2005 Apr;18(2):141-6
references.pmid: 15735418
references.citation: Arch Virol. 1998;143(4):781-7
references.pmid: 9638147
references.citation: Vet Microbiol. 2000 May 22;74(1-2):3-13
references.pmid: 10799774
references.citation: J Gen Virol. 2005 Mar;86(Pt 3):727-731
references.pmid: 15722533
references.citation: Proc Natl Acad Sci U S A. 2008 May 27;105(21):7558-63
references.pmid: 18508975
references.citation: Vaccine. 2003 May 16;21(17-18):1974-9
references.pmid: 12706686
references.citation: MMWR Morb Mortal Wkly Rep. 2004 Apr 9;53(13):284-7
references.pmid: 15071427
references.citation: J Virol. 2004 Jan;78(2):995-8
references.pmid: 14694130