| Abstract |
Dr. DeGroot has sought to determine whether
clade B vaccines will be useful in the context of non-clade-B
challenges. Her lab has engaged in an assessment of existing
HIV vaccine candidates for their potential to stimulate cross-protective
immune responses and examination of the sequences of HIV isolates
from other regions of the world for T cell epitopes that are
either wholly or partially conserved in candidate HIV vaccines.
Validating the potential for HIV vaccines to stimulate cross-reactive
responses, and identifying new CTL epitopes that are conserved
across HIV-1 clades are pursuits that will enhance the development
and deployment of HIV vaccines that are relevant in the context
of the global HIV epidemic. The purpose of in vitro epitope
screening studies carried out under her CFAR developmental
funding has been to confirm that Conservatrix and EpiMatrix
permit the selection of highly conserved HIV-1 epitopes from
among tens of millions of epitope candidates (40,000 HIV-1
sequences x average 600 amino acids per sequence x 10mer overlapping
frames). The only alternative to using Conservatrix and EpiMatrix
to define epitopes that are relevant across clades is to perform
epitope mapping using thousands of peptides and thousands
of study volunteers. The data suggest that Conservatrix and
EpiMatrix provide a much more efficient means of identifying
epitope candidates. Dr. De Groot's lab has confirmed, in pilot
studies, that 40% of epitopes selected using these tools stimulate
ELISpot responses. They also reconfirmed other published reports
describing immune responses to diverse, sometimes subdominant
epitopes (average of 2.47 responses per subject). It is likely
that these preliminary results, performed on PBMC from a relatively
small study subject sample, actually underestimate the number
of epitopes selected using the tools they have developed.
Dr. DeGroot has secured NIH funding on several projects as
a co-investigator and PI, including R01 AI45416 and R01 AI40888.
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