|
|
|
Controversial topics and findings of high interest
This page is under constant reconstruction.
Do you agree or disagree?
E-mail your opinion to the Webmaster, who will place your comment next to the commented comment!
Suggestions are welcome.
vol 73, April 2000
edited by D. Paton and S. Edwards
http://www.elsevier.nl/locate/vetmic/
In this study, a new generation of DNA vaccines established. Bacterial artificial chromosome-(BAC)-propagated, packaging-defective herpes simplex viral genomic DNA (fHSVDpac) was attached to gold particles and used for DNA immunization (BAC-vac). This new type of vaccine was able to induce: (i) ex vivo HSV—1 specific CTL—activity detected in lymph node - or spleen cells; (ii) the production of IgG2a antibodies in wt - as well as interferon g-receptor deficient mice, and (iii) protection against an i.c. challenge with wt HSV—1 at a dose of 200 LD50.
Advantageous to the new system is that fHSVDpac DNA can easily be manipulated to accommodate heterologous genes or to modify the HSV—1 genome itself because the DNA can be maintained and amplified as a stable plasmid in E. coli. In addition, bacterially amplified DNA may be more stable than eukaryotically propagated DNA, thus, suffering less damage upon attachment to gold particles. This may explain the fact that the BAC-vac technology was able to bring the size of successful DNA vaccinations to new dimensions (>160 kbp).
The immunity achieved by 1.5 mg of fHSVDpac DNA was equally effective as infection with 109 p.f.u. of DISC HSV—1. By contrast, non-replicating particles devoid of the viral genome were unable to induce detectable CTL-activity or Ab formation. Similarly, others have shown previously that mice immunized with a conventional DNA vaccine, containing either the HSV—1 gB or gD genes, induced strong Ab responses associated with CD4+ T cells but CTLs were not always detected.
Since immunization with BAC-vac alone, in the absence of any homologous or heterologous helpervirus, did induce a Th1-like response associated with strong CTL-activity, this new method of DNA vaccination appears not only effective but also biologically safe.
Furthermore, a modified BAC-vac could be used simultaneously as an adjuvant and as a vector for heterologous gene expression. Thus, effective immune responses may be achieved against targets such as tumors where potent CTL immunity with a Th1-phenotype is considered important for the treatment.
| Click button to go |
 |
back to our home page |