# PROJECT 1: Design of native-like SOSIP trimers

> **NIH NIH P01** · WEILL MEDICAL COLL OF CORNELL UNIV · 2021 · $1,047,229

## Abstract

Project 1 Abstract
The goals of Project 1 are to design and evaluate new versions of SOSIP trimers based on a range of HIV-1 genes
with mutations to improve their structural, antigenic and immunogenic properties. The trimers designed in
Project 1, with structure-based input from Project 2, are produced by Core B, provided to Project 2 for structural
studies, assessed for antigenicity by Project 1, and sent to multiple collaborators for additional research,
including animal immunogenicity studies. Project 1 will be closely involved in the overall scientific program. Dr.
John P. Moore, will direct Project 1, at the Weill Cornell Medical College, New York. Dr. Rogier W. Sanders
will lead a component at the Amsterdam University Medical Centers, Amsterdam. The Specific Aims are:
 Aim 1: To design Env trimers that can induce bNAb responses. We will design new and redesign
existing SOSIP trimers by using high-resolution structures and animal immunogenicity data. We will create
SOSIP trimer variants that target germline bNAb precursors (gl-bNAbs). We will further improve the overall
SOSIP trimer “recipe” for use with any given Env sequence, as trimers from multiple clades are likely to be
necessary to steer NAb responses towards breadth. We will focus responses to bNAb epitopes on SOSIP trimers,
by eliminating unwanted holes in glycan shields and by masking non-NAb epitopes that may act as decoys,
including neo-epitopes on the trimer base. The overall goals are to better present mature-bNAb and gl-bNAb
epitopes to the immune system, and drive Ab evolution toward bNAb development.
 Aim 2: To enhance the potency and durability of antibody responses by presenting SOSIP
trimers particulate immunogens and incorporating T-helper epitopes. We will chemically couple
SOSIP trimers to Iron Oxide nanoparticles (NP, 25-50 nm) to use as immunogens for priming antibody
responses. To compensate for well-known deficiencies in endogenous Env-encoded T-cell helper epitopes, we
will incorporate exogenous T-cell helper epitopes into the soluble and NP-presented SOSIP trimers. The overall
goals are to overcome limitations to the immunogenicity of HIV-1 Env proteins in general.
 Aim 3: To design and evaluate animal immunogenicity studies using SOSIP trimers. Our team
has well-established collaborations with several groups as well as access to other non-NIH funding support that
together enable it to conduct animal immunization studies that are not directly paid for by this award. Project 1
will work with collaborators to design immunogenicity experiments and contribute to the analysis and
interpretation of these studies by performing neutralization, NAb-epitope mapping and related serology
assays. The overall goals are to further advance the design of SOSIP trimers and trimer-based vaccination
regimens that are capable of inducing bNAbs.

## Key facts

- **NIH application ID:** 10083181
- **Project number:** 5P01AI110657-07
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** JOHN P MOORE
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,047,229
- **Award type:** 5
- **Project period:** 2015-06-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10083181

## Citation

> US National Institutes of Health, RePORTER application 10083181, PROJECT 1: Design of native-like SOSIP trimers (5P01AI110657-07). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10083181. Licensed CC0.

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