Improved NYVAC-based vaccine vectors

Karen Kibler, Carmen E. Gomez, Beatriz Perdiguero, Shukmei Wong, Trung Huynh, Susan Holechek, William Arndt, Victoria Jimenez, Ruben Gonzalez-Sanz, Karen Denzler, Elias K. Haddad, Ralf Wagner, Rafick P. Sékaly, James Tartaglia, Giuseppe Pantaleo, Bertram Jacobs, Mariano Esteban

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Abstract

While as yet there is no vaccine against HIV/AIDS, the results of the phase III Thai trial (RV144) have been encouraging and suggest that further improvements of the prime/boost vaccine combination of a poxvirus and protein are needed. With this aim, in this investigation we have generated derivatives of the candidate vaccinia virus vaccine vector NYVAC with potentially improved functions. This has been achieved by the re-incorporation into the virus genome of two host range genes, K1L and C7L, in conjunction with the removal of the immunomodulatory viral molecule B19, an antagonist of type I interferon action. These novel virus vectors, referred to as NYVAC-C-KC and NYVAC-C-KC-ΔB19R, have acquired relevant biological characteristics, giving higher levels of antigen expression in infected cells, replication-competency in human keratinocytes and dermal fibroblasts, activation of selective host cell signal transduction pathways, and limited virus spread in tissues. Importantly, these replication-competent viruses have been demonstrated to maintain a highly attenuated phenotype.

Original languageEnglish (US)
Article numbere25674
JournalPloS one
Volume6
Issue number11
DOIs
StatePublished - Nov 9 2011

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Kibler, K., Gomez, C. E., Perdiguero, B., Wong, S., Huynh, T., Holechek, S., Arndt, W., Jimenez, V., Gonzalez-Sanz, R., Denzler, K., Haddad, E. K., Wagner, R., Sékaly, R. P., Tartaglia, J., Pantaleo, G., Jacobs, B., & Esteban, M. (2011). Improved NYVAC-based vaccine vectors. PloS one, 6(11), [e25674]. https://doi.org/10.1371/journal.pone.0025674