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

Alan G Goodman; Paul P Heinen; Susana Guerra; Aneesh Vijayan; Carlos Oscar S Sorzano; Carmen E Gomez; Mariano Esteban

doi:10.1371/journal.pone.0025938

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

Journal article

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

Alan G Goodman, Paul P Heinen, Susana Guerra, Aneesh Vijayan, Carlos Oscar S Sorzano, Carmen E Gomez and Mariano Esteban

PloS one, Vol.6(10), pp.e25938-e25938

2011

DOI: https://doi.org/10.1371/journal.pone.0025938

Handle:

https://hdl.handle.net/2376/106186

PMCID: PMC3187825

PMID: 21998725

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Abstract

Vaccination

Viral Proteins - immunology

Molecular Sequence Data

Vaccinia virus - genetics

Orthomyxoviridae - immunology

CD4-Positive T-Lymphocytes - immunology

Epitopes - immunology

Lung - virology

Amino Acid Sequence

Cell Line

DNA, Recombinant - genetics

Viral Proteins - chemistry

Viral Proteins - genetics

Viral Load - immunology

Antigens, Viral - immunology

Animals

Influenza Vaccines - immunology

Influenza Vaccines - genetics

Dogs

Influenza Vaccines - chemistry

T-Lymphocytes - immunology

Mice

CD8-Positive T-Lymphocytes - immunology

Lung - immunology

Orthomyxoviridae - physiology

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 IFNγ-secreting splenocytes, composed of populations marked by CD4(+) and CD8(+) T cells producing IFNγ or TNFα. 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.

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Title: A human multi-epitope recombinant vaccinia virus as a universal T cell vaccine candidate against influenza virus
Creators: Alan G Goodman - Department of Cellular and Molecular Biology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas, Madrid, Spain
Paul P Heinen
Susana Guerra
Aneesh Vijayan
Carlos Oscar S Sorzano
Carmen E Gomez
Mariano Esteban
Publication Details: PloS one, Vol.6(10), pp.e25938-e25938
Academic Unit: School of Molecular Biosciences
Publisher: Public Library Science; United States
Number of pages: 11
Grant note: Marcelino Botin Foundation CSIC-FSE / Ministry of Science and Education of Spain; Spanish Government La Caixa Foundation FIS 2009-80145 / Spanish Ministry of Health Ramon y Cajal Program
Identifiers: 99900546974101842
Language: English
Resource Type: Journal article