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Annual and Interim Progress Report Summaries

Principal Investigator: Ellis Reinherz

Project: Broadly Neutralizing Antibodies Against Clade C HIV-1 Isolates

Submitted July 2, 2012

The overarching goal of this project is to elicit broadly neutralizing anti-HIV-1 antibodies to the distal membrane proximal ectodomain region (MPER) of gp41 predicated on i) structure-based immunogen design and ii) nanoparticle delivery through targeted uptake. NMR and EPR-based structural analysis demonstrates the presence of a hinge between the N and C helical segments of the MPER of additional clade C HIV-1 sequences studied in the context of the lipid membrane. Immunogenicity studies are well underway but already demonstrate that presentation of the MPER embedded on lipid-based particles/liposomes stimulates B cell responses capable of recognizing this segment. This response is absolutely specific. In fact, immunogenicity is predicated on membrane presentation in precise terms, so that the form of membrane adduction, chemical linkers and/or modifications all effect immunogenicity. The ability to produce MPER-TM protein is now critical to afford new insights both into structural biology as well as immunogen design. The latter will be incorporated into liposome-based MPER presentation during the current year.

Submitted July 1, 2011
Submitted July 9, 2010
Submitted December 21, 2010 (Interim Report)
Submitted July 9, 2010
Submitted December 30, 2009 (Interim Report)
Submitted July 1, 2009
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