# PROJECT 2:Structural studies of SOSIP trimers

> **NIH NIH P01** · WEILL MEDICAL COLL OF CORNELL UNIV · 2021 · $1,217,315

## Abstract

Project 2 Abstract
Project 2 will generate structural information to validate and improve the design of new generations of SOSIP
trimers in close interaction with Project 1 and Core B. Project 2 will take a highly integrative approach involving
cryo- and negative-stain-electron microscopy (NS-EM), X-ray crystallography and a range of other biophysical
tools (SEC-MALS, ITC, DSC and SPR) to provide a comprehensive biophysical understanding of trimers and
trimer-bnAb complexes. The data will be shared with Project 1 to improve the stability, antigenicity and
immunogenicity of new SOSIP trimer designs. Dr. Ian A. Wilson will direct Project 2 at The Scripps Research
Institute and Dr. Andrew B. Ward will be co-Leader. The Specific Aims are:
 Aim 1: To biophysically and structurally characterize new SOSIP trimers, including germline
targeting SOSIP trimers. We will generate high-resolution structures by cryo-EM or X-ray crystallography
to enable further engineering SOSIP trimers, and low-resolution structures by NS-EM to provide rapid feedback
about the quality of SOSIP trimers. We will also use NS-EM to assess the quality of trimers after stress tests that
mimic vaccine storage and formulation conditions such as the effect of adjuvant mixing. These assays are critical
prior to animal immunization studies, to ensure only high-quality trimers are evaluated.
 Aim 2: To determine high-resolution structures of SHIV infection-elicited, vaccine-induced
NAbs, or naïve precursor antibodies isolated with GT-SOSIP trimers. We will solve structures of
neutralizing Abs (NAbs) isolated from trimer-immunized and SHIV-infected animals to assess their similarity to
known bNAbs and their potential for developing breadth. The goals are to further optimize the presentation of
bNAb epitopes on SOSIP trimers and facilitate the design of sets or series of trimers for steering responses toward
bnAbs in prime-boost-boost strategies that mimic infection. We will solve structures of SOSIP trimer complexes
with germline precursor antibodies to compare with affinity-matured bnAbs. The goal is to design SOSIP trimer
boosts for guiding precursor antibodies toward breadth.
 Aim 3: To design, optimize and determine structures of SOSIP trimers displayed on
nanoparticle platforms. We will incorporate SOSIP trimers into various proteinaceous nanoparticles (NPs),
such as the two-component self-assembling NPs, via an iterative cycle of structure-based design and testing. The
goal is to preserve the desirable antigenic properties of SOSIP trimers, while gaining the immunological benefits
of particulate antigen presentation. Working with Project 1 and Core B, we will evaluate a range of designs and
thereby generate an arsenal of SOSIP-NP immunogens that will be tested in animals. The outcomes of those
studies will further guide the design of new SOSIP-NP constructs.

## Key facts

- **NIH application ID:** 10083182
- **Project number:** 5P01AI110657-07
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** IAN A WILSON
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,217,315
- **Award type:** 5
- **Project period:** 2015-06-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10083182

## Citation

> US National Institutes of Health, RePORTER application 10083182, PROJECT 2:Structural studies of SOSIP trimers (5P01AI110657-07). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10083182. Licensed CC0.

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