I know nada about AGEN. I should know tons, but I know nada.
But, while poking around, I ran into this. I assume it's relevant (I may be way off base), and.... since AGEN is on your list........
J Immunol 2001 May 15;166(10):6218-26
Enhancement of Sindbis virus self-replicating RNA vaccine potency by
linkage of Mycobacterium tuberculosis heat shock protein 70 gene to an
antigen gene.
Cheng WF, Hung CF, Chai CY, Hsu KF, He L, Rice CM, Ling M, Wu TC.
Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 21205, USA.
Recently, self-replicating RNA vaccines (RNA replicons) have emerged as an effective strategy
for nucleic acid vaccine development. Unlike naked DNA vaccines, RNA replicons eventually
cause lysis of transfected cells and therefore do not raise the concern of integration into the host
genome. We evaluated the effect of linking human papillomavirus type 16 E7 as a model Ag to
Mycobacterium tuberculosis heat shock protein 70 (HSP70) on the potency of Ag-specific
immunity generated by a Sindbis virus self-replicating RNA vector, SINrep5. Our results
indicated that this RNA replicon vaccine containing an E7/HSP70 fusion gene generated
significantly higher E7-specific T cell-mediated immune responses in vaccinated mice than did
vaccines containing the wild-type E7 gene. Furthermore, our in vitro studies demonstrated that
E7 Ag from E7/HSP70 RNA replicon-transfected cells can be processed by bone
marrow-derived dendritic cells and presented more efficiently through the MHC class I pathway
than can wild-type E7 RNA replicon-transfected cells. More importantly, the fusion of HSP70 to
E7 converted a less effective vaccine into one with significant potency against E7-expressing
tumors. This antitumor effect was dependent on NK cells and CD8(+) T cells. These results
indicated that fusion of HSP70 to an Ag gene may greatly enhance the potency of self-replicating
RNA vaccines. |
