title: 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 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.
authors: Department of Cellular and Molecular Biology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas, Madrid, Spain.
authors: Alan G
authors: AG
authors: Goodman
authors: Paul P
authors: PP
authors: Heinen
authors: Susana
authors: S
authors: Guerra
authors: Aneesh
authors: A
authors: Vijayan
authors: Carlos Oscar S
authors: CO
authors: Sorzano
authors: Carmen E
authors: CE
authors: Gomez
authors: Mariano
authors: M
authors: Esteban
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D004274:DNA, Recombinant / Q000235:genetics*; D004285:Dogs; D000939:Epitopes / Q000276:immunology*; D006801:Humans; D007252:Influenza Vaccines / Q000737:chemistry / Q000235:genetics* / Q000276:immunology*; D008168:Lung / Q000276:immunology / Q000821:virology; D051379:Mice; D008969:Molecular Sequence Data; D009975:Orthomyxoviridae / Q000276:immunology* / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology*; D014611:Vaccination; D014616:Vaccinia virus / Q000235:genetics*; D019562:Viral Load / Q000276:immunology; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology
chemical_list: D000956:Antigens, Viral; D004274:DNA, Recombinant; D000939:Epitopes; D007252:Influenza Vaccines; D014764:Viral Proteins