Dataset Information

Protection against mouse and avian influenza A strains via vaccination with a combination of conserved proteins NP, M1 and NS1.

ABSTRACT:

Background

Experimental data accumulated over more than a decade indicate that cross-strain protection against influenza may be achieved by immunization with conserved influenza proteins. At the same time, the efficacy of immunization schemes designed along these lines and involving internal influenza proteins, mostly NP and M1, has not been sufficient.

Objective

To test the immunogenicity and protective efficacy of DNA vaccination with a combination of NP, M1 and NS1 genes of influenza virus.

Methods

The immunogenicity and protective efficacy of DNA vaccination with NP, M1 and NS1 was tested in mice and chickens. Mice were challenged with mouse-adapted viral strains H3N2 and H5N2 and chicken challenged with avian H5N3 virus.

Results

In these settings, wild-type NS1 did not impede the cellular and humoral response to NP/M1 immunization in vivo. Moreover, addition of NS1-encoding plasmid to the NP/M1 immunization protocol resulted in a significantly increased protective efficacy in vivo.

Conclusions

The addition of NS1 to an influenza immunization regimen based on conserved proteins bears promise. It is feasible that upon further genetic modification of these and additional conserved influenza proteins, providing for their higher safety, expression and immunogenicity, a recombinant vaccine based on several structural and non-structural proteins or their epitopes will offer broad anti-influenza protection in a wide range of species.

SUBMITTER: Zhirnov OP

PROVIDER: S-EPMC2040185 | biostudies-literature | 2007 Mar

REPOSITORIES: biostudies-literature

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Publications

Protection against mouse and avian influenza A strains via vaccination with a combination of conserved proteins NP, M1 and NS1.

Zhirnov Oleg P OP Isaeva Elena I EI Konakova Tatyana E TE Thoidis Galini G Piskareva Lyudmila M LM Akopova Irina I II Kartashov Alex A Altstein Anatoly D AD Ilyinskii Petr O PO Shneider Alexander M AM

Influenza and other respiratory viruses 20070301 2

<h4>Background</h4>Experimental data accumulated over more than a decade indicate that cross-strain protection against influenza may be achieved by immunization with conserved influenza proteins. At the same time, the efficacy of immunization schemes designed along these lines and involving internal influenza proteins, mostly NP and M1, has not been sufficient.<h4>Objective</h4>To test the immunogenicity and protective efficacy of DNA vaccination with a combination of NP, M1 and NS1 genes of inf ...[more]

PMID: 18784792

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Project description:Seasonal influenza virus infections cause significant morbidity and mortality every year. Annual influenza virus vaccines are effective but only when well matched with circulating strains. Therefore, there is an urgent need for better vaccines that induce broad protection against drifted seasonal and emerging pandemic influenza viruses. One approach to design such vaccines is based on targeting conserved regions of the influenza virus hemagglutinin. Sequential vaccination with chimeric hemagglutinin constructs can refocus antibody responses towards the conserved immunosubdominant stalk domain of the hemagglutinin, rather than the variable immunodominant head. A complementary approach for a universal influenza A virus vaccine is to induce T-cell responses to conserved internal influenza virus antigens. For this purpose, replication deficient recombinant viral vectors based on Chimpanzee Adenovirus Oxford 1 and Modified Vaccinia Ankara virus are used to express the viral nucleoprotein and the matrix protein 1. In this study, we combined these two strategies and evaluated the efficacy of viral vectors expressing both chimeric hemagglutinin and nucleoprotein plus matrix protein 1 in a mouse model against challenge with group 2 influenza viruses including H3N2, H7N9 and H10N8. We found that vectored vaccines expressing both sets of antigens provided enhanced protection against H3N2 virus challenge when compared to vaccination with viral vectors expressing only one set of antigens. Vaccine induced antibody responses against divergent group 2 hemagglutinins, nucleoprotein and matrix protein 1 as well as robust T-cell responses to the nucleoprotein and matrix protein 1 were detected. Of note, it was observed that while antibodies to the H3 stalk were already boosted to high levels after two vaccinations with chimeric hemagglutinins (cHAs), three exposures were required to induce strong reactivity across subtypes. Overall, these results show that a combinations of different universal influenza virus vaccine strategies can induce broad antibody and T-cell responses and can provide increased protection against influenza.

Dataset Information

Protection against mouse and avian influenza A strains via vaccination with a combination of conserved proteins NP, M1 and NS1.

Background

Objective

Methods

Results

Conclusions

Publications

Protection against mouse and avian influenza A strains via vaccination with a combination of conserved proteins NP, M1 and NS1.

Similar Datasets

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