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Immunogenicity and Cross Protection in Mice Afforded by Pandemic H1N1 Live Attenuated Influenza Vaccine Containing Wild-Type Nucleoprotein

Identifieur interne : 000297 ( Main/Exploration ); précédent : 000296; suivant : 000298

Immunogenicity and Cross Protection in Mice Afforded by Pandemic H1N1 Live Attenuated Influenza Vaccine Containing Wild-Type Nucleoprotein

Auteurs : Andrey Rekstin [Russie] ; Irina Isakova-Sivak [Russie] ; Galina Petukhova [Russie] ; Daniil Korenkov [Russie] ; Igor Losev [Russie] ; Tatiana Smolonogina [Russie] ; Tatiana Tretiak [Russie] ; Svetlana Donina [Russie] ; Svetlana Shcherbik [États-Unis] ; Tatiana Bousse [États-Unis] ; Larisa Rudenko [Russie]

Source :

RBID : PMC:5292185

Abstract

Since conserved viral proteins of influenza virus, such as nucleoprotein (NP) and matrix 1 protein, are the main targets for virus-specific CD8+ cytotoxic T-lymphocytes (CTLs), we hypothesized that introduction of the NP gene of wild-type virus into the genome of vaccine reassortants could lead to better immunogenicity and afford better protection. This paper describes in vitro and in vivo preclinical studies of two new reassortants of pandemic H1N1 live attenuated influenza vaccine (LAIV) candidates. One had the hemagglutinin (HA) and neuraminidase (NA) genes from A/South Africa/3626/2013 H1N1 wild-type virus on the A/Leningrad/134/17/57 master donor virus backbone (6 : 2 formulation) while the second had the HA, NA, and NP genes of the wild-type virus on the same backbone (5 : 3 formulation). Although both LAIVs induced similar antibody immune responses, the 5 : 3 LAIV provoked greater production of virus-specific CTLs than the 6 : 2 variant. Furthermore, the 5 : 3 LAIV-induced CTLs had higher in vivo cytotoxic activity, compared to 6 : 2 LAIV. Finally, the 5 : 3 LAIV candidate afforded greater protection against infection and severe illness than the 6 : 2 LAIV. Inclusion in LAIV of the NP gene from wild-type influenza virus is a new approach to inducing cross-reactive cell-mediated immune responses and cross protection against pandemic influenza.


Url:
DOI: 10.1155/2017/9359276
PubMed: 28210631
PubMed Central: 5292185


Affiliations:


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Le document en format XML

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<p>Since conserved viral proteins of influenza virus, such as nucleoprotein (NP) and matrix 1 protein, are the main targets for virus-specific CD8+ cytotoxic T-lymphocytes (CTLs), we hypothesized that introduction of the NP gene of wild-type virus into the genome of vaccine reassortants could lead to better immunogenicity and afford better protection. This paper describes in vitro and in vivo preclinical studies of two new reassortants of pandemic H1N1 live attenuated influenza vaccine (LAIV) candidates. One had the hemagglutinin (HA) and neuraminidase (NA) genes from A/South Africa/3626/2013 H1N1 wild-type virus on the A/Leningrad/134/17/57 master donor virus backbone (6 : 2 formulation) while the second had the HA, NA, and NP genes of the wild-type virus on the same backbone (5 : 3 formulation). Although both LAIVs induced similar antibody immune responses, the 5 : 3 LAIV provoked greater production of virus-specific CTLs than the 6 : 2 variant. Furthermore, the 5 : 3 LAIV-induced CTLs had higher in vivo cytotoxic activity, compared to 6 : 2 LAIV. Finally, the 5 : 3 LAIV candidate afforded greater protection against infection and severe illness than the 6 : 2 LAIV. Inclusion in LAIV of the NP gene from wild-type influenza virus is a new approach to inducing cross-reactive cell-mediated immune responses and cross protection against pandemic influenza.</p>
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</back>
</TEI>
<affiliations>
<list>
<country>
<li>Russie</li>
<li>États-Unis</li>
</country>
<region>
<li>Géorgie (États-Unis)</li>
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</list>
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<country name="Russie">
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<name sortKey="Losev, Igor" sort="Losev, Igor" uniqKey="Losev I" first="Igor" last="Losev">Igor Losev</name>
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<country name="États-Unis">
<region name="Géorgie (États-Unis)">
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<name sortKey="Bousse, Tatiana" sort="Bousse, Tatiana" uniqKey="Bousse T" first="Tatiana" last="Bousse">Tatiana Bousse</name>
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</record>

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