A live attenuated H7N7 candidate vaccine virus induces neutralizing antibody that confers protection from challenge in mice, ferrets, and monkeys.
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.
Min
Ji-Young
JY
LID, NIAID, NIH, Bethesda, MD 20892, USA.
Vogel
Leatrice
L
Matsuoka
Yumiko
Y
Lu
Bin
B
Swayne
David
D
Jin
Hong
H
Kemble
George
G
Subbarao
Kanta
K
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
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
Vaccine. 2008 Mar 25;26(14):1742-50
18336962
J Virol. 2003 Dec;77(24):13399-402
14645595
Proc Natl Acad Sci U S A. 2004 Feb 3;101(5):1356-61
14745020
Virology. 2008 Aug 15;378(1):123-32
18585748
Cell. 1987 Aug 28;50(5):665-6
3304656
Vaccine. 2004 Oct 22;22(31-32):4137-8
15474703
MMWR Morb Mortal Wkly Rep. 2004 Jul 2;53(25):547-52
15229411
Vaccine. 2003 Oct 1;21(27-30):4430-6
14505926
J Virol. 2007 Oct;81(19):10558-66
17634234
Virology. 1981 Sep;113(2):725-35
7023022
J Virol. 2010 Feb;84(3):1289-301
19906920
Vaccine. 2009 Jun 8;27(28):3744-53
19464558
Vaccine. 2009 Mar 18;27(13):1889-97
19368768
Virology. 2003 Feb 1;306(1):18-24
12620793
Proc Natl Acad Sci U S A. 2000 May 23;97(11):6108-13
10801978
Arch Virol. 2000;145(5):1047-58
10881690
Influenza Other Respir Viruses. 2007 Jul;1(4):157-66
19432631
Nat Rev Immunol. 2007 Apr;7(4):267-78
17363960
Emerg Infect Dis. 2004 Dec;10(12):2196-9
15663860
Virus Res. 1997 Jun;49(2):173-86
9213392
J Infect Dis. 2009 Mar 1;199(5):711-6
19210163
Vet Pathol. 1994 Mar;31(2):237-45
8203087
Emerg Infect Dis. 2006 Jan;12(1):66-72
16494720
Vaccine. 2009 Aug 6;27(36):4953-60
19540952
Emerg Infect Dis. 2004 Apr;10(4):693-9
15200862
Lancet. 1996 Sep 28;348(9031):901-2
8826845
J Virol. 2005 Oct;79(19):12401-7
16160167
Virology. 2009 Dec 20;395(2):280-8
19833372
Clin Vaccine Immunol. 2007 Nov;14(11):1425-32
17913860
N Engl J Med. 2008 Jan 17;358(3):261-73
18199865
Lancet. 2004 Feb 21;363(9409):587-93
14987882
J Immunol. 1997 Feb 1;158(3):1222-30
9013963
PLoS Med. 2006 Sep;3(9):e360
16968127
Curr Opin Infect Dis. 2005 Apr;18(2):141-6
15735418
Arch Virol. 1998;143(4):781-7
9638147
Vet Microbiol. 2000 May 22;74(1-2):3-13
10799774
J Gen Virol. 2005 Mar;86(Pt 3):727-731
15722533
Proc Natl Acad Sci U S A. 2008 May 27;105(21):7558-63
18508975
Vaccine. 2003 May 16;21(17-18):1974-9
12706686
MMWR Morb Mortal Wkly Rep. 2004 Apr 9;53(13):284-7
15071427
J Virol. 2004 Jan;78(2):995-8
14694130