Development of a recombinant HSP110- XXXX /neu vaccine using the chaperoning properties of HSP110.

@entity1 @entity404 @entity5 @entity1457 @entity379 @entity19262 @entity405 @entity1722
Several studies have shown that when purified from a @entity5 , certain @entity1457 proteins (HSPs) can function as effective vaccines against the same @entity5 by virtue of their ability to bind @entity5 -specific peptides. However, only a small fraction of the associated peptides would be expected to be immunogenic, in addition to which, the clinical application of this vaccine requires the availability of a surgical specimen of sufficient quantity for purification of the HSP. The present study describes a new approach for the development of natural HSP vaccines that do not have these limitations. This approach uses a recombinant HSP that is noncovalently bound to a recombinant @entity5 protein antigen by @entity1457 . HSP110 has been selected for this purpose, because it has been shown to be a highly efficient molecular chaperone in binding to large protein substrates. We show that a "natural chaperone complex" between HSP110 and the @entity19262 ( @entity19262 ) of @entity1 @entity1722 protein ( @entity1722 )/neu is formed by @entity1457 . This HSP110- @entity19262 vaccine elicited both @entity405 (+) and @entity404 (+) T-cell responses against @entity19262 as determined by an antigen-specific @entity379 production in an enzyme-linked immunospot assay (ELISPOT). In vivo depletion studies revealed that the @entity405 (+) T-cell response was independent of @entity404 (+) T-cell help. The HSP110- @entity19262 complex also significantly enhanced @entity19262 -specific antibody responses relative to that seen with @entity19262 alone. No @entity405 (+) T cell or antibody response was detected against HSP110. The use of recombinant HSP110 to form natural chaperone complexes with large protein antigens represents a new and powerful approach for the design of protein-targeted @entity5 vaccines.
