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Principal Investigator: JOHN P MOORE
Organization: WEILL MEDICAL COLL OF CORNELL UNIV
Fiscal Year: 2021
Award: $680,752
Funding agency: National Institute of Allergy and Infectious Diseases
Overall Abstract
This HIVRAD Program Project renewal application is made in response to PAR-18-319. It contains two Research
Projects, one Scientific Core and an Administrative Core, under the direction of Principal Investigator, John P.
Moore, PhD (Weill Cornell Medical College; WCMC) and co-Principal Investigator, Ian A. Wilson, PhD (The
Scripps Research Institute; TSRI). The goal of the project is to further develop stable, soluble, cleaved trimeric
mimics of the native Env spike (SOSIP trimers) as antigens for structural studies and as immunogens for the
development of vaccines aimed at inducing broadly neutralizing antibodies (bNAbs).
Our central hypothesis is that a proteolytically cleaved, soluble, trimeric form of HIV-1 Env is an
appropriate structural antigen for high resolution x-ray crystallography and electron microscopy studies, and a
suitable immunogen for vaccine research aimed at the induction of bNAbs. Our intent is to use structure-based
information to help develop an effective, prophylactic HIV-1 vaccine (or component of a more complex vaccine)
that is based on the concept of inducing sufficient titers of bNAbs. We believe that one way to accomplish this
goal is to make soluble recombinant protein mimics of the native, trimeric Env spike that is present on virions,
that mediates virus entry into cells and that is the target for all known bNAbs. SOSIP trimers have the desired
properties and can be produced efficiently, including in the amounts and qualities required for human clinical
trials.
This HIVRAD project team has made excellent progress during the past 4 years, and now seeks support
to continue to work together. Its research plan involves the following sub-components.
Project 1: John P. Moore (and Rogier W. Sanders): Design of SOSIP trimers
Project 2: Ian A. Wilson (and Andrew B. Ward): Structural studies of SOSIP trimers
Core B: PJ Klasse: Production of SOSIP trimers
Core A: John P. Moore: Administrative support
Rogier W. Sanders of the Amsterdam University Medical Centers, Amsterdam will direct a sub-component of
Project 1.
Andrew B. Ward of The Scripps Research Institute will be the co-leader of Project 2.
As well as the integral components of the HIVRAD team, we propose to maintain and expand an extensive
network of research collaborations, and we will continue to provide SOSIP trimers and related reagents to the
many scientists who request our support.
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