The CD4 Induced Conformation:
CD4 binding to HIV-1 gp120 elicits conformational rearrangements revealing or creating unique epitopes characteristic of the CD4-gp120 complex. These CD4i epitopes serve as effective targets for the development of an HIV vaccine.
Epitope Based Vaccines:
Classical vaccines implement killed or attentuated viruses or their subunits as vaccine immunogens. Discovery of the cognate epitope of broadly neutralizing antibodies provides the option of developing a vaccine immunogen that consists of isolated reconstituted neutralizing epitopes. Hence the immune response is focused precisely on the virus' most sensitive targets. For this we have developed the means to computationally discover epitopes and then functionally reconstitute them.
Human polyclonal serum consists of millions of different antibodies. The repertoire of these millions of immunoglobulins constitutes the "IgOme". The IgOme thus represents a historical and updated record of our humoral response towards viral infections. Profiling the IgOme provides a wealth of information, such as the correlates of effective immunity towards specific viruses and a high resolution evaluation of the response towards vaccination. Profiling the IgOme is possible by combining phage display peptide technology with Next Generation DNA sequencing.
Serological immunodiagnostics is based on the ability to detect virus-specific antibodies in serum. These antibodies bind to specific virus-antigenic markers. Each marker can be measured as "Specific" and "Sensitive" - however no marker is ever 100% Specific (ie, 0 false positive signals) or 100% Sensitive (ie, 0 false negative signals). Scoring the signal for an array of epitope markers provides enhance diagnostic power and allows high resolution multiplex diagnosis of multiple viral infections in a signal blood sample. The implementation of high throughput multiplex combinatorial diagnostics will have enormous impact of blood transfusion safety.