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A live attenuated H7N7 candidate vaccine virus induces neutralizing antibody that confers protection from challenge in mice, ferrets, and monkeys.

Identifieur interne : 000F07 ( Main/Exploration ); précédent : 000F06; suivant : 000F08

A live attenuated H7N7 candidate vaccine virus induces neutralizing antibody that confers protection from challenge in mice, ferrets, and monkeys.

Auteurs : Ji-Young Min [États-Unis] ; Leatrice Vogel ; Yumiko Matsuoka ; Bin Lu ; David Swayne ; Hong Jin ; George Kemble ; Kanta Subbarao

Source :

RBID : pubmed:20810733

Descripteurs français

English descriptors

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.

DOI: 10.1128/JVI.01305-10
PubMed: 20810733


Affiliations:


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Le document en format XML

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<term>Chick Embryo</term>
<term>Chickens</term>
<term>Chlorocebus aethiops</term>
<term>Disease Models, Animal</term>
<term>Female</term>
<term>Ferrets</term>
<term>Hemagglutinin Glycoproteins, Influenza Virus (administration & dosage)</term>
<term>Hemagglutinin Glycoproteins, Influenza Virus (genetics)</term>
<term>Hemagglutinin Glycoproteins, Influenza Virus (immunology)</term>
<term>Humans</term>
<term>Influenza A Virus, H7N7 Subtype (immunology)</term>
<term>Influenza Vaccines (administration & dosage)</term>
<term>Influenza Vaccines (adverse effects)</term>
<term>Influenza Vaccines (genetics)</term>
<term>Influenza Vaccines (immunology)</term>
<term>Influenza, Human (immunology)</term>
<term>Influenza, Human (prevention & control)</term>
<term>Influenza, Human (virology)</term>
<term>Male</term>
<term>Mice</term>
<term>Mice, Inbred BALB C</term>
<term>Neuraminidase (administration & dosage)</term>
<term>Neuraminidase (genetics)</term>
<term>Neuraminidase (immunology)</term>
<term>Vaccines, Attenuated (administration & dosage)</term>
<term>Vaccines, Attenuated (adverse effects)</term>
<term>Vaccines, Attenuated (genetics)</term>
<term>Vaccines, Attenuated (immunology)</term>
<term>Viral Proteins (administration & dosage)</term>
<term>Viral Proteins (genetics)</term>
<term>Viral Proteins (immunology)</term>
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<term>Anticorps antiviraux (immunologie)</term>
<term>Anticorps neutralisants (immunologie)</term>
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<term>Femelle</term>
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<term>Protéines virales (génétique)</term>
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<term>Sialidase (génétique)</term>
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<div type="abstract" xml:lang="en">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.</div>
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