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PLoS One. 2011;6(11):e25674. doi: 10.1371/journal.pone.0025674. Epub 2011 Nov 9.

Improved NYVAC-based vaccine vectors.

Author information

1
The Biodesign Institute at Arizona State University, Tempe, Arizona, United States of America.

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.

PMID:
22096477
PMCID:
PMC3212513
DOI:
10.1371/journal.pone.0025674
[Indexed for MEDLINE]
Free PMC Article

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