A human multi-epitope recombinant vaccinia virus as a universal T cell vaccine candidate against influenza virus
EntityUAM. Departamento de Medicina Preventiva y Salud Pública y Microbiología
PublisherPublic Library of Science
10.1371/journal.pone.0025938Plos One 6.10 (2011): e25938
Funded byThis work was supported by Ministry of Science and Education of Spain Program JAE-DOC (CSIC-FSE) (to A.G.G), Spanish Ministry of Health Ramón y Cajal Program (FIS 2009-80145) (to S.G.), La Caixa Foundation International PhD Program Fellowship (to A.V.), and SAF-2008-02036 and the Marcelino Botín Foundation (to M.E.)
SubjectsAmino Acid Sequence; Influenza Vaccines; CD8-Positive T-Lymphocytes; Orthomyxoviridae; Cell Line; Medicina
Rights© 2011 Goodman et al.
Esta obra está bajo una Licencia Creative Commons Atribución 4.0 Internacional.
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
Google Scholar:Goodman, Alan G. - Heinen, Paul P. - Guerra, Susana M. - Vijayan, Aneesh - Sorzano, Carlos Oscar S. - Gómez, Carmen Elena - Estéban, Mariano R.
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