Construction and characterization of replication competent attenuated NYVAC-based vectors as potential HIV vaccines : OA021-01

Details

Serval ID
serval:BIB_C361DEFA7CC4
Type
Inproceedings: an article in a conference proceedings.
Publication sub-type
Abstract (Abstract): shot summary in a article that contain essentials elements presented during a scientific conference, lecture or from a poster.
Collection
Publications
Institution
Title
Construction and characterization of replication competent attenuated NYVAC-based vectors as potential HIV vaccines : OA021-01
Title of the conference
AIDS Vaccine 2009
Author(s)
Jacobs B., Kibler K., Wong S., Huynh T., Holechek S., Denzler K., Arndt W., Parrington M., Tartaglia J., Pantaleo G.
Address
Paris, France, October 19-22, 2009
ISBN
1742-4690
Publication state
Published
Issued date
2009
Peer-reviewed
Oui
Volume
6
Series
Retrovirology
Pages
O13
Language
english
Notes
Background : Poxvirus viruses have been utilized for many years as vaccine vectors. Recent years have seen an increase in efforts to identify safer pox vectors to express heterologous antigens, in this case HIV antigens. Safer pox vectors have included MVA, ALVAC and NYVAC, which are all replication deficient in human cells. However, the loss of replication competence has also reduced antigen expression, and therefore, immunologic response to the vaccination. We have constructed vectors in a NYVAC background that are replication competent but attenuated for virulence.
Methods : To restore replication competence in NYVAC that expresses clade C HIV gag, pol, nef and env (NYVAC-C), we inserted genes deleted in the parental vector: 1) NYVAC-C-KC includes the human host range genes K1L and C7L; 2) NYVAC-C+12 includes the entire cassette of genes from K1L to C7L that is deleted from NYVAC. To decrease virulence, we deleted the E3L gene, which is required for interferon-resistance and virulence, and replaced it with a gene from Ambystoma tigrinum virus (ATV, the new virus is NYVAC-C+12-ATV), which restores a single round of replication.
Results : In vitro characterization of the constructs demonstrates restoration of replication in primary and human cell lines. NYVAC-C+12-ATV leads to induction of pro-inflammatory signal transduction pathways. Pathogenicity studies in newborn mice demonstrate attenuation of 3-5 logs when compared to wt vaccinia virus or to NYCBH.
Conclusion : NYVAC constructs provide increased safety in the most sensitive of animal models. Because antigen expression is increased in these replication-competent constructs, they may be more immunogenic than replication-defective poxvirus vectors. Increased pro-inflammatory signal transduction in cells infected with NYVAC-C+12-ATV may also lead to an increase in immunogenicity of this highly attenuated vector. Thus, these replication competent, attenuated viral vectors may have improved immunogenicity over replication defective poxvirus vectors, while maintaining an improved safety profile.
Web of science
Open Access
Yes
Create date
21/12/2009 11:08
Last modification date
20/08/2019 15:38
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