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A human multi-epitope recombinant vaccinia virus as a universal T cell vaccine candidate against influenza virus.

ABSTRACT: There is a need to develop a universal vaccine against influenza virus infection to avoid developing new formulations of a seasonal vaccine each year. Many of the vaccine strategies for a universal vaccine target strain-conserved influenza virus proteins, such as the matrix, polymerase, and nucleoproteins, rather than the surface hemagglutinin and neuraminidase proteins. In addition, non-disease-causing viral vectors are a popular choice as a delivery system for the influenza virus antigens. As a proof-of-concept, we have designed a novel influenza virus immunogen based on the NP backbone containing human T cell epitopes for M1, NS1, NP, PB1 and PA proteins (referred as NPmix) as well as a construct containing the conserved regions of influenza virus neuraminidase (N-terminal) and hemagglutinin (C-terminal) (referred as NA-HA). DNA vectors and vaccinia virus recombinants expressing NPmix (WR-NP) or both NPmix plus NA-HA (WR-flu) in the cytosol were tested in a heterologous DNA-prime/vaccinia virus-boost vaccine regimen in mice. We observed an increase in the number of influenza virus-specific IFN?-secreting splenocytes, composed of populations marked by CD4(+) and CD8(+) T cells producing IFN? or TNF?. Upon challenge with influenza virus, the vaccinated mice exhibited decreased viral load in the lungs and a delay in mortality. These findings suggest that DNA prime/poxvirus boost with human multi-epitope recombinant influenza virus proteins is a valid approach for a general T-cell vaccine to protect against influenza virus infection.

SUBMITTER: Goodman AG

PROVIDER: S-EPMC3187825 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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A human multi-epitope recombinant vaccinia virus as a universal T cell vaccine candidate against influenza virus.

Goodman Alan G AG Heinen Paul P PP Guerra Susana S Vijayan Aneesh A Sorzano Carlos Oscar S CO Gomez Carmen E CE Esteban Mariano M

PloS one 20111005 10

There is a need to develop a universal vaccine against influenza virus infection to avoid developing new formulations of a seasonal vaccine each year. Many of the vaccine strategies for a universal vaccine target strain-conserved influenza virus proteins, such as the matrix, polymerase, and nucleoproteins, rather than the surface hemagglutinin and neuraminidase proteins. In addition, non-disease-causing viral vectors are a popular choice as a delivery system for the influenza virus antigens. As ...[more]

PMID: 21998725

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Project description:BackgroundInfluenza A virus is one of the leading causes of annual mortality. The emerging of novel escape variants of the influenza A virus is still a considerable challenge in the annual process of vaccine production. The evolution of vaccines ranks among the most critical successes in medicine and has eradicated numerous infectious diseases. Recently, multi-epitope vaccines, which are based on the selection of epitopes, have been increasingly investigated.ResultsThis study utilized an immunoinformatic approach to design a recombinant multi-epitope vaccine based on a highly conserved epitope of hemagglutinin, neuraminidase, and membrane matrix proteins with fewer changes or mutate over time. The potential B cells, cytotoxic T lymphocytes (CTL), and CD4 T cell epitopes were identified. The recombinant multi-epitope vaccine was designed using specific linkers and a proper adjuvant. Moreover, some bioinformatics online servers and datasets were used to evaluate the immunogenicity and chemical properties of selected epitopes. In addition, Universal Immune System Simulator (UISS) in silico trial computational framework was run after influenza exposure and recombinant multi-epitope vaccine administration, showing a good immune response in terms of immunoglobulins of class G (IgG), T Helper 1 cells (TH1), epithelial cells (EP) and interferon gamma (IFN-g) levels. Furthermore, after a reverse translation (i.e., convertion of amino acid sequence to nucleotide one) and codon optimization phase, the optimized sequence was placed between the two EcoRV/MscI restriction sites in the PET32a+ vector.ConclusionsThe proposed "Recombinant multi-epitope vaccine" was predicted with unique and acceptable immunological properties. This recombinant multi-epitope vaccine can be successfully expressed in the prokaryotic system and accepted for immunogenicity studies against the influenza virus at the in silico level. The multi-epitope vaccine was then tested with the Universal Immune System Simulator (UISS) in silico trial platform. It revealed slight immune protection against the influenza virus, shedding the light that a multistep bioinformatics approach including molecular and cellular level is mandatory to avoid inappropriate vaccine efficacy predictions.

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A human multi-epitope recombinant vaccinia virus as a universal T cell vaccine candidate against influenza virus.

Publications

A human multi-epitope recombinant vaccinia virus as a universal T cell vaccine candidate against influenza virus.

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