Serveur d'exploration H2N2

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The influence of the multi-basic cleavage site of the H5 hemagglutinin on the attenuation, immunogenicity and efficacy of a live attenuated influenza A H5N1 cold-adapted vaccine virus

Identifieur interne : 001030 ( Main/Exploration ); précédent : 001029; suivant : 001031

The influence of the multi-basic cleavage site of the H5 hemagglutinin on the attenuation, immunogenicity and efficacy of a live attenuated influenza A H5N1 cold-adapted vaccine virus

Auteurs : Amorsolo L. Suguitan ; Michael P. Marino ; Purvi D. Desai ; Li-Mei Chen ; Yumiko Matsuoka ; Ruben O. Donis ; Hong Jin ; David E. Swayne ; George Kemble ; Kanta Subbarao

Source :

RBID : PMC:2787913

Descripteurs français

English descriptors

Abstract

A recombinant live attenuated influenza virus ΔH5N1 vaccine with a modified hemagglutinin (HA) and intact neuraminidase genes from A/Vietnam/1203/04 (H5N1) and six remaining genome segments from A/Ann Arbor/6/60 (H2N2) cold-adapted (AA ca) virus was previously shown to be attenuated in chickens, mice and ferrets. Evaluation of the recombinant H5N1 viruses in mice indicated that three independent factors contributed to the attenuation of the ΔH5N1 vaccine: the attenuating mutations specified by the AA ca loci had the greatest influence, followed by the deletion of the H5 HA multi-basic cleavage site (MBS), and the constellation effects of the AA genes acting in concert with the H5N1 glycoproteins. Restoring the MBS in the H5 HA of the vaccine virus improved its immunogenicity and efficacy, likely as a consequence of increased virus replication, indicating that removal of the MBS had a deleterious effect on the immunogenicity and efficacy of the ΔH5N1 vaccine in mice.


Url:
DOI: 10.1016/j.virol.2009.09.017
PubMed: 19833372
PubMed Central: 2787913


Affiliations:


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<term>Cold Temperature</term>
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<term>Femelle</term>
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<term>Viral Proteins</term>
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<term>Vaccins atténués</term>
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<p id="P4">A recombinant live attenuated influenza virus ΔH5N1 vaccine with a modified hemagglutinin (HA) and intact neuraminidase genes from A/Vietnam/1203/04 (H5N1) and six remaining genome segments from A/Ann Arbor/6/60 (H2N2) cold-adapted (AA
<italic>ca</italic>
) virus was previously shown to be attenuated in chickens, mice and ferrets. Evaluation of the recombinant H5N1 viruses in mice indicated that three independent factors contributed to the attenuation of the ΔH5N1 vaccine: the attenuating mutations specified by the AA
<italic>ca</italic>
loci had the greatest influence, followed by the deletion of the H5 HA multi-basic cleavage site (MBS), and the constellation effects of the AA genes acting in concert with the H5N1 glycoproteins. Restoring the MBS in the H5 HA of the vaccine virus improved its immunogenicity and efficacy, likely as a consequence of increased virus replication, indicating that removal of the MBS had a deleterious effect on the immunogenicity and efficacy of the ΔH5N1 vaccine in mice.</p>
</div>
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<name sortKey="Donis, Ruben O" sort="Donis, Ruben O" uniqKey="Donis R" first="Ruben O." last="Donis">Ruben O. Donis</name>
<name sortKey="Jin, Hong" sort="Jin, Hong" uniqKey="Jin H" first="Hong" last="Jin">Hong Jin</name>
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